Donald W. Black, MD

“I did not like those patients… They made me angry and I found myself irritated to experience them as they seemed so distant from myself and from all that is human. This is an astonishing intolerance which brands me a poor psychiatrist.”

Sigmund Freud, Letter to István Hollós (1928)

While Freud was referring to psychotic patients,¹ his evident frustration shows that difficult and challenging patients have vexed even the best of us. All physicians and other clinicians will experience patient encounters that lead to anger or frustration, or even challenge their sense of equanimity and professional identity. In short, difficult and challenging patient interactions are unavoidable, regardless of the physician’s discipline.^2-5 At times, physicians might struggle with demanding, unpleasant, ungrateful, and possibly dangerous patients, while sometimes the struggle is with the patient’s family members. No physician is immune to the problem, which makes it crucial to learn to anticipate and manage difficult patient interactions, skills which are generally not taught in medical schools or residency programs.

One prospective study of clinic patients found that up to 15% of patient encounters are deemed “difficult.”⁶ Common scenarios include patients (or their relatives) who seek certain tests after researching symptoms online, threats of legal or social media action in response to feeling that the physician is not listening to them, demands for a second opinion after disagreeing with the physician’s diagnosis, and mistrust of doctors after presenting with symptoms and not receiving a diagnosis. It is also common to care for patients who focus on negative outcomes or fail to adhere to treatment recommendations. These encounters can make physicians feel stressed out, disrespected, abused, or even fearful if threatened. Some physicians may come to feel they are trapped in a hostile work environment with little support from their supervisors or administrators. Patients often have a complaint office or department to turn to, but there is no equivalent for physicians, who are expected to soldier on regardless.

This article highlights a model that describes poor physician-patient encounters, factors contributing to these issues, how to manage these difficult interactions, and what to do if the relationship cannot be remediated.

Describing the ‘difficult’ patient

In a landmark 1978 paper, Groves⁷ provided one of the first descriptions of “difficult” patients. His colorful observations continue to provide useful insights. Groves emphasized that most medical texts ignore the issue of difficult patients and provide little or no guidance—which is still true 43 years later. He observed that physicians cannot avoid occasional negative feelings toward some patients. Further, Groves suggested that countertransference is often at the root of hateful reactions, a process he defines as “conscious or unconscious unbidden and unwanted hostile or sexual feelings toward the patient.”⁷Table 1⁷ outlines how Groves divided “hateful” patients into several categories, and how physicians might respond to such patients.

A model for understanding difficult patient encounters

Adams and Murray² created a model to help explain interactions with difficult or challenging patients that consists of 3 elements: the patient, the physician, and the system (ie, situation or environment). Hull and Broquet⁸ and Hardavella et al⁹ later adapted the model and described its components (Table 2^2,8,9).

Continue to: When considering...

When considering difficult interactions, it is important to be aware that all 3 components could interact, or merely 1 or 2 could come into play, but all should be explored as possible contributing factors.

Patient factors

The patient’s role in initiating or maintaining a problematic interaction should be explored. While some physicians are tempted to conclude that a personality disorder underlies difficult interactions, research shows a more complex picture. First, not all difficult patients have a psychiatric disorder, let alone a personality disorder. Jackson and Kroenke⁶ reported that among 74 difficult patients in an ambulatory clinic, 29% had a depressive disorder or anxiety disorder, with 11% experiencing 2 or more disorders. Major depressive disorder was present in 8.4% patients, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2%.⁶ These researchers found that difficult patient interactions were associated with the presence of a psychiatric disorder, especially depressive or anxiety disorders, and multiple physical symptoms.

Importantly, difficult patients are not unique to psychiatry, and are found in all medical disciplines and every type of practice situation. Some problematic patients have a substance use disorder, and their difficulty might stem from intoxication, withdrawal, or drug-seeking behaviors. Psychotic disorders can be the source of difficult interactions, typically resulting from the patient’s symptoms (ie, hallucinations, delusions, or bizarre behavior). Physicians tend to be forgiving toward these patients because they understand the extent of the individual’s illness. The same is true for a patient with dementia, who might be disruptive and loud, yet clearly is not in control of their behavior.

Koekkoek et al⁵ reviewed 94 articles that focused on difficult patients seen in mental health settings. Most patients were male (60% to 68%), and most were age 26 to 32 years. Diagnoses of psychotic disorders and personality disorders were the most frequent, while mood and other disorders were less common. In 1 of the studies reviewed, 6% of psychiatric inpatients were considered difficult. Koekkoek et al⁵ proposed that there are 3 groups of difficult patients:

• care avoiders: patients with psychosis who lack insight
• care seekers: patients who are chronically ill who have trouble maintaining a steady relationship with their caregivers
• care claimers: patients who do not require long-term care, but need housing, medication, or a “declaration of incompetence.”

Physician factors

Physicians are frequent contributors to bad interactions with their patients.^2,7,8 They can become angry or defensive because of burnout, stress, or frustration, which might lead them to snap or otherwise respond inappropriately to their patients. Many physicians are overworked, sleep-deprived, or busier than they would prefer. Personal problems can be preoccupying and contribute to a physician being ill-tempered or distracted (eg, marital or family problems). Some physicians are simply poor communicators and might not understand the need to adapt their communication style to their patient, instead using medical jargon the patient does not understand. Ideally, physicians should modify their language to suit the patient’s level of education, degree of medical sophistication, and cultural background.

Continue to: A physician's personality traits...

A physician’s personality traits could clash with those of the patient, particularly if the physician is especially rigid or obsessional. Rather than “going with the flow,” the overly rigid physician might become impatient with patients who fail to understand diagnostic assessments or treatment recommendations. Inefficient physicians might not be able to keep up with the daily schedule, which could fuel impatience and perhaps even lead them to think that the patient is taking too much of their valuable time. Some might not know how to convey empathy, for example when giving bad news (“The tests show you have cancer…”). Others fail to make consistent eye contact with patients without understanding its importance to communication, a problem made worse by the use of electronic medical record systems (EMRs).

Systems issues

Systems issues also contribute to suboptimal physician-patient interactions, and some issues can be attributed to administrative problems. Examples of systems issues include:

• when a patient has difficulty making an appointment and is forced to listen to a confusing menu of choices
• a busy clinic that can only offer a patient an appointment 6 months away
• crowded or noisy waiting rooms
• language barriers for patients whose primary langage is not English. Not having access to an interpreter can exacerbate their frustration
• the use of EMRs is a growing threat to positive physician-patient interactions, yet their influence is often ignored. Widely disliked by physicians,¹⁰ EMRs are required in all but the smallest independent practice settings. Many busy physicians focus their attention on the computer, giving the patient the impression that the physician is not listening to them. Many patients conclude that they are less important than the process.

The consequences of difficult interactions

Following a bad interaction, dissatisfied patients are more likely to leave the clinic or hospital and ignore medical advice. These patients might then show up in crowded emergency departments, which may lead to poor use of health care resources. For physicians, challenging situations sap their emotional energy, cause demoralization, and interfere with their sense of job fulfillment. In extreme cases, such feelings might lead the physician to dislike and even avoid the patient.

How to manage challenging situations

Taking the following steps can help physicians work through challenging situations with their patients.

Diagnose the problem. First, recognize the difficult situation, analyze it, and identify how the patient, the physician, and the system are contributing to a bad physician-patient interaction. Diagnosing the interactional difficulty should precede the diagnosis and management of the patient’s disease. Physicians should acknowledge their own contribution through their attitude or actions. Finally, determine if there are system issues that are contributing to the problem, or if it is the clinic or inpatient setting itself (eg, noisy inpatient unit).

Continue to: Maintain your cool

Maintain your cool. With any difficult interaction, a physician’s first obligation is to remain calm and professional, while modeling appropriate behavior. If the patient is angry or emotionally intense, talking over them or interrupting them only makes the situation worse. Try to see the interaction from the patient’s perspective. Both parties should work together to find a common ground.

Collaborate, respect boundaries, and empathize. One study of a group of 100 family physicians found that having the following 3 skills were essential to successfully managing situations with difficult patients^11,12:

• the ability to collaborate (vs opposition)
• the appropriate use of power (vs misuse of power, or violation of boundaries by either party)
• the ability to empathize, which for most physicians involves understanding and validating the patient’s subjective experiences.

Although a description of the many facets of empathy (cognitive, affective, motivational) is beyond the scope of this article, it is worth pointing out that a patient’s positive perception of their physician’s empathy improves not only patient satisfaction but health outcomes.¹³ The Box describes a difficult patient whose actions changed through the collaboration and empathy of his treatment team.

Box 1

Verbalize the difficulty. It is important to openly discuss the problem. For example, “We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?” This approach names the “elephant in the room” and avoids casting blame. It also creates a sense of shared ownership by externalizing the problem from both the patient and physician. Verbalizing the difficulty can help build trust and pave the way to working together toward a common solution.

Consider other explanations for the patient’s behavior. For example, anger directed at a physician could be due to anxiety about an unrelated matter, such as the patient’s recent job loss or impending divorce. Psychiatrists might understand this behavior better as displacement, which is considered a maladaptive defense mechanism. It is important to listen to the patient and offer empathy, which will help the patient feel supported and build a rapport that can help to resolve the encounter.

Continue to: When helping patients...

When helping patients with multiple issues, which is a common scenario, the physician might start by asking, “What would you like to address today?”¹⁴ Keep a list of the issues so you do not forget the patient’s concerns, and then ask: “What do you think is going on?” Give patients time to verbalize their concerns. Physicians should:

• validate concerns: “I understand where you’re coming from.”
• offer empathy: “I can see how difficult this has been for you.”
• reframe: “Let me make sure I hear you correctly.”
• refocus: “Let’s agree on what we need to do at this visit.”

Find common ground. When the patient and physician have different ideas on diagnosis or treatment, finding common ground is another way to resolve a difficult encounter. Difficulties arise when there appears to be little common ground, which often results from unrealistic expectations. Patients might be seen as “demanding” or “manipulative”’ if they push for a diagnosis or treatment the doctor is not comfortable with. As soon as there is some overlap and common ground, the difficulty rapidly subsides.

Set clear boundaries and limits. Physicians should set limits on what patient behavior might “cross the line.” A “behavioral contract” (or “treatment contract”) can help by setting explicit expectations. For example, showing up late for appointments or inappropriately seeking drugs of abuse (eg, opioids, benzodiazepines) might be identified as violations of the contract. Once the contract is set, the patient should be asked to restate key components. Clarify any confusion or barriers to compliance and define clear expectations. The patient should be informed of potential consequences of contract violations, including termination.

Staff members involved in the patient’s care should agree with the terms of any behavioral contract, and should receive a copy of it. Patients should have “buy in,” meaning that they have had an opportunity to provide input to the contract and have agreed to its elements. Both the physician and patient should sign the document.

When all else fails

When there is a breakdown in rapport that makes it difficult or impossible to continue offering treatment, consider termination. This could be due to threatening or abusive patient behavior, sexual advances, repeated no-shows, treatment noncompliance that jeopardizes patient safety, refusal to follow the treatment plan, or violating the terms of a behavioral contract. In some settings, it might be the failure to pay bills.

Continue to: If a patient is unable to...

If a patient is unable to follow the contract, the physician should explore possible extenuating circumstances. The physician should seek to remedy the problem and involve other team members if possible (eg, case manager, nurse), advising a patient about behaviors that could lead to termination.

If the problem is irremediable, notify the patient in writing, give them time to find another physician, and facilitate the transfer of care.¹⁵ Take steps to prevent the patient from running out of any medications associated with withdrawal or discontinuation syndromes (eg, selective serotonin reuptake inhibitors, benzodiazepines) during the care transition. While there is no requirement regarding the amount of time allowed, at least 30 days is typical.

Bottom Line

Difficult patient interactions are common and unavoidable. Physicians should acknowledge and recognize contributing factors in such encounters—including their own role. When handling such situations, physicians should remain calm and model appropriate behavior. Improving communication, offering empathy, and validating the patient’s concerns can help resolve factors that contribute to poor patient interactions. If efforts to remediate the physician-patient relationship fail, termination may be necessary.

Related Resources

• Koekkoek B, Berno van Meijel CNS, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57(6):795-802.
• Pereira MR, Figueiredo AF. Challenging patient-doctor interactions in psychiatry – difficult patient syndrome. European Psychiatry. 2017;41(supplement):S719. doi. org/10.1016/j.eurpsy.2017.01.1297

“I did not like those patients… They made me angry and I found myself irritated to experience them as they seemed so distant from myself and from all that is human. This is an astonishing intolerance which brands me a poor psychiatrist.”

Sigmund Freud, Letter to István Hollós (1928)

While Freud was referring to psychotic patients,¹ his evident frustration shows that difficult and challenging patients have vexed even the best of us. All physicians and other clinicians will experience patient encounters that lead to anger or frustration, or even challenge their sense of equanimity and professional identity. In short, difficult and challenging patient interactions are unavoidable, regardless of the physician’s discipline.^2-5 At times, physicians might struggle with demanding, unpleasant, ungrateful, and possibly dangerous patients, while sometimes the struggle is with the patient’s family members. No physician is immune to the problem, which makes it crucial to learn to anticipate and manage difficult patient interactions, skills which are generally not taught in medical schools or residency programs.

One prospective study of clinic patients found that up to 15% of patient encounters are deemed “difficult.”⁶ Common scenarios include patients (or their relatives) who seek certain tests after researching symptoms online, threats of legal or social media action in response to feeling that the physician is not listening to them, demands for a second opinion after disagreeing with the physician’s diagnosis, and mistrust of doctors after presenting with symptoms and not receiving a diagnosis. It is also common to care for patients who focus on negative outcomes or fail to adhere to treatment recommendations. These encounters can make physicians feel stressed out, disrespected, abused, or even fearful if threatened. Some physicians may come to feel they are trapped in a hostile work environment with little support from their supervisors or administrators. Patients often have a complaint office or department to turn to, but there is no equivalent for physicians, who are expected to soldier on regardless.

This article highlights a model that describes poor physician-patient encounters, factors contributing to these issues, how to manage these difficult interactions, and what to do if the relationship cannot be remediated.

Describing the ‘difficult’ patient

In a landmark 1978 paper, Groves⁷ provided one of the first descriptions of “difficult” patients. His colorful observations continue to provide useful insights. Groves emphasized that most medical texts ignore the issue of difficult patients and provide little or no guidance—which is still true 43 years later. He observed that physicians cannot avoid occasional negative feelings toward some patients. Further, Groves suggested that countertransference is often at the root of hateful reactions, a process he defines as “conscious or unconscious unbidden and unwanted hostile or sexual feelings toward the patient.”⁷Table 1⁷ outlines how Groves divided “hateful” patients into several categories, and how physicians might respond to such patients.

A model for understanding difficult patient encounters

Adams and Murray² created a model to help explain interactions with difficult or challenging patients that consists of 3 elements: the patient, the physician, and the system (ie, situation or environment). Hull and Broquet⁸ and Hardavella et al⁹ later adapted the model and described its components (Table 2^2,8,9).

Continue to: When considering...

When considering difficult interactions, it is important to be aware that all 3 components could interact, or merely 1 or 2 could come into play, but all should be explored as possible contributing factors.

Patient factors

The patient’s role in initiating or maintaining a problematic interaction should be explored. While some physicians are tempted to conclude that a personality disorder underlies difficult interactions, research shows a more complex picture. First, not all difficult patients have a psychiatric disorder, let alone a personality disorder. Jackson and Kroenke⁶ reported that among 74 difficult patients in an ambulatory clinic, 29% had a depressive disorder or anxiety disorder, with 11% experiencing 2 or more disorders. Major depressive disorder was present in 8.4% patients, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2%.⁶ These researchers found that difficult patient interactions were associated with the presence of a psychiatric disorder, especially depressive or anxiety disorders, and multiple physical symptoms.

Importantly, difficult patients are not unique to psychiatry, and are found in all medical disciplines and every type of practice situation. Some problematic patients have a substance use disorder, and their difficulty might stem from intoxication, withdrawal, or drug-seeking behaviors. Psychotic disorders can be the source of difficult interactions, typically resulting from the patient’s symptoms (ie, hallucinations, delusions, or bizarre behavior). Physicians tend to be forgiving toward these patients because they understand the extent of the individual’s illness. The same is true for a patient with dementia, who might be disruptive and loud, yet clearly is not in control of their behavior.

Koekkoek et al⁵ reviewed 94 articles that focused on difficult patients seen in mental health settings. Most patients were male (60% to 68%), and most were age 26 to 32 years. Diagnoses of psychotic disorders and personality disorders were the most frequent, while mood and other disorders were less common. In 1 of the studies reviewed, 6% of psychiatric inpatients were considered difficult. Koekkoek et al⁵ proposed that there are 3 groups of difficult patients:

• care avoiders: patients with psychosis who lack insight
• care seekers: patients who are chronically ill who have trouble maintaining a steady relationship with their caregivers
• care claimers: patients who do not require long-term care, but need housing, medication, or a “declaration of incompetence.”

Physician factors

Physicians are frequent contributors to bad interactions with their patients.^2,7,8 They can become angry or defensive because of burnout, stress, or frustration, which might lead them to snap or otherwise respond inappropriately to their patients. Many physicians are overworked, sleep-deprived, or busier than they would prefer. Personal problems can be preoccupying and contribute to a physician being ill-tempered or distracted (eg, marital or family problems). Some physicians are simply poor communicators and might not understand the need to adapt their communication style to their patient, instead using medical jargon the patient does not understand. Ideally, physicians should modify their language to suit the patient’s level of education, degree of medical sophistication, and cultural background.

Continue to: A physician's personality traits...

A physician’s personality traits could clash with those of the patient, particularly if the physician is especially rigid or obsessional. Rather than “going with the flow,” the overly rigid physician might become impatient with patients who fail to understand diagnostic assessments or treatment recommendations. Inefficient physicians might not be able to keep up with the daily schedule, which could fuel impatience and perhaps even lead them to think that the patient is taking too much of their valuable time. Some might not know how to convey empathy, for example when giving bad news (“The tests show you have cancer…”). Others fail to make consistent eye contact with patients without understanding its importance to communication, a problem made worse by the use of electronic medical record systems (EMRs).

Systems issues

Systems issues also contribute to suboptimal physician-patient interactions, and some issues can be attributed to administrative problems. Examples of systems issues include:

• when a patient has difficulty making an appointment and is forced to listen to a confusing menu of choices
• a busy clinic that can only offer a patient an appointment 6 months away
• crowded or noisy waiting rooms
• language barriers for patients whose primary langage is not English. Not having access to an interpreter can exacerbate their frustration
• the use of EMRs is a growing threat to positive physician-patient interactions, yet their influence is often ignored. Widely disliked by physicians,¹⁰ EMRs are required in all but the smallest independent practice settings. Many busy physicians focus their attention on the computer, giving the patient the impression that the physician is not listening to them. Many patients conclude that they are less important than the process.

The consequences of difficult interactions

Following a bad interaction, dissatisfied patients are more likely to leave the clinic or hospital and ignore medical advice. These patients might then show up in crowded emergency departments, which may lead to poor use of health care resources. For physicians, challenging situations sap their emotional energy, cause demoralization, and interfere with their sense of job fulfillment. In extreme cases, such feelings might lead the physician to dislike and even avoid the patient.

How to manage challenging situations

Taking the following steps can help physicians work through challenging situations with their patients.

Diagnose the problem. First, recognize the difficult situation, analyze it, and identify how the patient, the physician, and the system are contributing to a bad physician-patient interaction. Diagnosing the interactional difficulty should precede the diagnosis and management of the patient’s disease. Physicians should acknowledge their own contribution through their attitude or actions. Finally, determine if there are system issues that are contributing to the problem, or if it is the clinic or inpatient setting itself (eg, noisy inpatient unit).

Continue to: Maintain your cool

Maintain your cool. With any difficult interaction, a physician’s first obligation is to remain calm and professional, while modeling appropriate behavior. If the patient is angry or emotionally intense, talking over them or interrupting them only makes the situation worse. Try to see the interaction from the patient’s perspective. Both parties should work together to find a common ground.

Collaborate, respect boundaries, and empathize. One study of a group of 100 family physicians found that having the following 3 skills were essential to successfully managing situations with difficult patients^11,12:

• the ability to collaborate (vs opposition)
• the appropriate use of power (vs misuse of power, or violation of boundaries by either party)
• the ability to empathize, which for most physicians involves understanding and validating the patient’s subjective experiences.

Although a description of the many facets of empathy (cognitive, affective, motivational) is beyond the scope of this article, it is worth pointing out that a patient’s positive perception of their physician’s empathy improves not only patient satisfaction but health outcomes.¹³ The Box describes a difficult patient whose actions changed through the collaboration and empathy of his treatment team.

Box 1

Verbalize the difficulty. It is important to openly discuss the problem. For example, “We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?” This approach names the “elephant in the room” and avoids casting blame. It also creates a sense of shared ownership by externalizing the problem from both the patient and physician. Verbalizing the difficulty can help build trust and pave the way to working together toward a common solution.

Consider other explanations for the patient’s behavior. For example, anger directed at a physician could be due to anxiety about an unrelated matter, such as the patient’s recent job loss or impending divorce. Psychiatrists might understand this behavior better as displacement, which is considered a maladaptive defense mechanism. It is important to listen to the patient and offer empathy, which will help the patient feel supported and build a rapport that can help to resolve the encounter.

Continue to: When helping patients...

When helping patients with multiple issues, which is a common scenario, the physician might start by asking, “What would you like to address today?”¹⁴ Keep a list of the issues so you do not forget the patient’s concerns, and then ask: “What do you think is going on?” Give patients time to verbalize their concerns. Physicians should:

• validate concerns: “I understand where you’re coming from.”
• offer empathy: “I can see how difficult this has been for you.”
• reframe: “Let me make sure I hear you correctly.”
• refocus: “Let’s agree on what we need to do at this visit.”

Find common ground. When the patient and physician have different ideas on diagnosis or treatment, finding common ground is another way to resolve a difficult encounter. Difficulties arise when there appears to be little common ground, which often results from unrealistic expectations. Patients might be seen as “demanding” or “manipulative”’ if they push for a diagnosis or treatment the doctor is not comfortable with. As soon as there is some overlap and common ground, the difficulty rapidly subsides.

Set clear boundaries and limits. Physicians should set limits on what patient behavior might “cross the line.” A “behavioral contract” (or “treatment contract”) can help by setting explicit expectations. For example, showing up late for appointments or inappropriately seeking drugs of abuse (eg, opioids, benzodiazepines) might be identified as violations of the contract. Once the contract is set, the patient should be asked to restate key components. Clarify any confusion or barriers to compliance and define clear expectations. The patient should be informed of potential consequences of contract violations, including termination.

Staff members involved in the patient’s care should agree with the terms of any behavioral contract, and should receive a copy of it. Patients should have “buy in,” meaning that they have had an opportunity to provide input to the contract and have agreed to its elements. Both the physician and patient should sign the document.

When all else fails

When there is a breakdown in rapport that makes it difficult or impossible to continue offering treatment, consider termination. This could be due to threatening or abusive patient behavior, sexual advances, repeated no-shows, treatment noncompliance that jeopardizes patient safety, refusal to follow the treatment plan, or violating the terms of a behavioral contract. In some settings, it might be the failure to pay bills.

Continue to: If a patient is unable to...

If a patient is unable to follow the contract, the physician should explore possible extenuating circumstances. The physician should seek to remedy the problem and involve other team members if possible (eg, case manager, nurse), advising a patient about behaviors that could lead to termination.

If the problem is irremediable, notify the patient in writing, give them time to find another physician, and facilitate the transfer of care.¹⁵ Take steps to prevent the patient from running out of any medications associated with withdrawal or discontinuation syndromes (eg, selective serotonin reuptake inhibitors, benzodiazepines) during the care transition. While there is no requirement regarding the amount of time allowed, at least 30 days is typical.

Bottom Line

Difficult patient interactions are common and unavoidable. Physicians should acknowledge and recognize contributing factors in such encounters—including their own role. When handling such situations, physicians should remain calm and model appropriate behavior. Improving communication, offering empathy, and validating the patient’s concerns can help resolve factors that contribute to poor patient interactions. If efforts to remediate the physician-patient relationship fail, termination may be necessary.

Related Resources

• Koekkoek B, Berno van Meijel CNS, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57(6):795-802.
• Pereira MR, Figueiredo AF. Challenging patient-doctor interactions in psychiatry – difficult patient syndrome. European Psychiatry. 2017;41(supplement):S719. doi. org/10.1016/j.eurpsy.2017.01.1297

“I did not like those patients… They made me angry and I found myself irritated to experience them as they seemed so distant from myself and from all that is human. This is an astonishing intolerance which brands me a poor psychiatrist.”

Sigmund Freud, Letter to István Hollós (1928)

While Freud was referring to psychotic patients,¹ his evident frustration shows that difficult and challenging patients have vexed even the best of us. All physicians and other clinicians will experience patient encounters that lead to anger or frustration, or even challenge their sense of equanimity and professional identity. In short, difficult and challenging patient interactions are unavoidable, regardless of the physician’s discipline.^2-5 At times, physicians might struggle with demanding, unpleasant, ungrateful, and possibly dangerous patients, while sometimes the struggle is with the patient’s family members. No physician is immune to the problem, which makes it crucial to learn to anticipate and manage difficult patient interactions, skills which are generally not taught in medical schools or residency programs.

One prospective study of clinic patients found that up to 15% of patient encounters are deemed “difficult.”⁶ Common scenarios include patients (or their relatives) who seek certain tests after researching symptoms online, threats of legal or social media action in response to feeling that the physician is not listening to them, demands for a second opinion after disagreeing with the physician’s diagnosis, and mistrust of doctors after presenting with symptoms and not receiving a diagnosis. It is also common to care for patients who focus on negative outcomes or fail to adhere to treatment recommendations. These encounters can make physicians feel stressed out, disrespected, abused, or even fearful if threatened. Some physicians may come to feel they are trapped in a hostile work environment with little support from their supervisors or administrators. Patients often have a complaint office or department to turn to, but there is no equivalent for physicians, who are expected to soldier on regardless.

This article highlights a model that describes poor physician-patient encounters, factors contributing to these issues, how to manage these difficult interactions, and what to do if the relationship cannot be remediated.

Describing the ‘difficult’ patient

In a landmark 1978 paper, Groves⁷ provided one of the first descriptions of “difficult” patients. His colorful observations continue to provide useful insights. Groves emphasized that most medical texts ignore the issue of difficult patients and provide little or no guidance—which is still true 43 years later. He observed that physicians cannot avoid occasional negative feelings toward some patients. Further, Groves suggested that countertransference is often at the root of hateful reactions, a process he defines as “conscious or unconscious unbidden and unwanted hostile or sexual feelings toward the patient.”⁷Table 1⁷ outlines how Groves divided “hateful” patients into several categories, and how physicians might respond to such patients.

A model for understanding difficult patient encounters

Adams and Murray² created a model to help explain interactions with difficult or challenging patients that consists of 3 elements: the patient, the physician, and the system (ie, situation or environment). Hull and Broquet⁸ and Hardavella et al⁹ later adapted the model and described its components (Table 2^2,8,9).

Continue to: When considering...

When considering difficult interactions, it is important to be aware that all 3 components could interact, or merely 1 or 2 could come into play, but all should be explored as possible contributing factors.

Patient factors

The patient’s role in initiating or maintaining a problematic interaction should be explored. While some physicians are tempted to conclude that a personality disorder underlies difficult interactions, research shows a more complex picture. First, not all difficult patients have a psychiatric disorder, let alone a personality disorder. Jackson and Kroenke⁶ reported that among 74 difficult patients in an ambulatory clinic, 29% had a depressive disorder or anxiety disorder, with 11% experiencing 2 or more disorders. Major depressive disorder was present in 8.4% patients, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2%.⁶ These researchers found that difficult patient interactions were associated with the presence of a psychiatric disorder, especially depressive or anxiety disorders, and multiple physical symptoms.

Importantly, difficult patients are not unique to psychiatry, and are found in all medical disciplines and every type of practice situation. Some problematic patients have a substance use disorder, and their difficulty might stem from intoxication, withdrawal, or drug-seeking behaviors. Psychotic disorders can be the source of difficult interactions, typically resulting from the patient’s symptoms (ie, hallucinations, delusions, or bizarre behavior). Physicians tend to be forgiving toward these patients because they understand the extent of the individual’s illness. The same is true for a patient with dementia, who might be disruptive and loud, yet clearly is not in control of their behavior.

Koekkoek et al⁵ reviewed 94 articles that focused on difficult patients seen in mental health settings. Most patients were male (60% to 68%), and most were age 26 to 32 years. Diagnoses of psychotic disorders and personality disorders were the most frequent, while mood and other disorders were less common. In 1 of the studies reviewed, 6% of psychiatric inpatients were considered difficult. Koekkoek et al⁵ proposed that there are 3 groups of difficult patients:

• care avoiders: patients with psychosis who lack insight
• care seekers: patients who are chronically ill who have trouble maintaining a steady relationship with their caregivers
• care claimers: patients who do not require long-term care, but need housing, medication, or a “declaration of incompetence.”

Physician factors

Physicians are frequent contributors to bad interactions with their patients.^2,7,8 They can become angry or defensive because of burnout, stress, or frustration, which might lead them to snap or otherwise respond inappropriately to their patients. Many physicians are overworked, sleep-deprived, or busier than they would prefer. Personal problems can be preoccupying and contribute to a physician being ill-tempered or distracted (eg, marital or family problems). Some physicians are simply poor communicators and might not understand the need to adapt their communication style to their patient, instead using medical jargon the patient does not understand. Ideally, physicians should modify their language to suit the patient’s level of education, degree of medical sophistication, and cultural background.

Continue to: A physician's personality traits...

A physician’s personality traits could clash with those of the patient, particularly if the physician is especially rigid or obsessional. Rather than “going with the flow,” the overly rigid physician might become impatient with patients who fail to understand diagnostic assessments or treatment recommendations. Inefficient physicians might not be able to keep up with the daily schedule, which could fuel impatience and perhaps even lead them to think that the patient is taking too much of their valuable time. Some might not know how to convey empathy, for example when giving bad news (“The tests show you have cancer…”). Others fail to make consistent eye contact with patients without understanding its importance to communication, a problem made worse by the use of electronic medical record systems (EMRs).

Systems issues

Systems issues also contribute to suboptimal physician-patient interactions, and some issues can be attributed to administrative problems. Examples of systems issues include:

• when a patient has difficulty making an appointment and is forced to listen to a confusing menu of choices
• a busy clinic that can only offer a patient an appointment 6 months away
• crowded or noisy waiting rooms
• language barriers for patients whose primary langage is not English. Not having access to an interpreter can exacerbate their frustration
• the use of EMRs is a growing threat to positive physician-patient interactions, yet their influence is often ignored. Widely disliked by physicians,¹⁰ EMRs are required in all but the smallest independent practice settings. Many busy physicians focus their attention on the computer, giving the patient the impression that the physician is not listening to them. Many patients conclude that they are less important than the process.

The consequences of difficult interactions

Following a bad interaction, dissatisfied patients are more likely to leave the clinic or hospital and ignore medical advice. These patients might then show up in crowded emergency departments, which may lead to poor use of health care resources. For physicians, challenging situations sap their emotional energy, cause demoralization, and interfere with their sense of job fulfillment. In extreme cases, such feelings might lead the physician to dislike and even avoid the patient.

How to manage challenging situations

Taking the following steps can help physicians work through challenging situations with their patients.

Diagnose the problem. First, recognize the difficult situation, analyze it, and identify how the patient, the physician, and the system are contributing to a bad physician-patient interaction. Diagnosing the interactional difficulty should precede the diagnosis and management of the patient’s disease. Physicians should acknowledge their own contribution through their attitude or actions. Finally, determine if there are system issues that are contributing to the problem, or if it is the clinic or inpatient setting itself (eg, noisy inpatient unit).

Continue to: Maintain your cool

Maintain your cool. With any difficult interaction, a physician’s first obligation is to remain calm and professional, while modeling appropriate behavior. If the patient is angry or emotionally intense, talking over them or interrupting them only makes the situation worse. Try to see the interaction from the patient’s perspective. Both parties should work together to find a common ground.

Collaborate, respect boundaries, and empathize. One study of a group of 100 family physicians found that having the following 3 skills were essential to successfully managing situations with difficult patients^11,12:

• the ability to collaborate (vs opposition)
• the appropriate use of power (vs misuse of power, or violation of boundaries by either party)
• the ability to empathize, which for most physicians involves understanding and validating the patient’s subjective experiences.

Although a description of the many facets of empathy (cognitive, affective, motivational) is beyond the scope of this article, it is worth pointing out that a patient’s positive perception of their physician’s empathy improves not only patient satisfaction but health outcomes.¹³ The Box describes a difficult patient whose actions changed through the collaboration and empathy of his treatment team.

Box 1

Verbalize the difficulty. It is important to openly discuss the problem. For example, “We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?” This approach names the “elephant in the room” and avoids casting blame. It also creates a sense of shared ownership by externalizing the problem from both the patient and physician. Verbalizing the difficulty can help build trust and pave the way to working together toward a common solution.

Consider other explanations for the patient’s behavior. For example, anger directed at a physician could be due to anxiety about an unrelated matter, such as the patient’s recent job loss or impending divorce. Psychiatrists might understand this behavior better as displacement, which is considered a maladaptive defense mechanism. It is important to listen to the patient and offer empathy, which will help the patient feel supported and build a rapport that can help to resolve the encounter.

Continue to: When helping patients...

When helping patients with multiple issues, which is a common scenario, the physician might start by asking, “What would you like to address today?”¹⁴ Keep a list of the issues so you do not forget the patient’s concerns, and then ask: “What do you think is going on?” Give patients time to verbalize their concerns. Physicians should:

• validate concerns: “I understand where you’re coming from.”
• offer empathy: “I can see how difficult this has been for you.”
• reframe: “Let me make sure I hear you correctly.”
• refocus: “Let’s agree on what we need to do at this visit.”

Find common ground. When the patient and physician have different ideas on diagnosis or treatment, finding common ground is another way to resolve a difficult encounter. Difficulties arise when there appears to be little common ground, which often results from unrealistic expectations. Patients might be seen as “demanding” or “manipulative”’ if they push for a diagnosis or treatment the doctor is not comfortable with. As soon as there is some overlap and common ground, the difficulty rapidly subsides.

Set clear boundaries and limits. Physicians should set limits on what patient behavior might “cross the line.” A “behavioral contract” (or “treatment contract”) can help by setting explicit expectations. For example, showing up late for appointments or inappropriately seeking drugs of abuse (eg, opioids, benzodiazepines) might be identified as violations of the contract. Once the contract is set, the patient should be asked to restate key components. Clarify any confusion or barriers to compliance and define clear expectations. The patient should be informed of potential consequences of contract violations, including termination.

Staff members involved in the patient’s care should agree with the terms of any behavioral contract, and should receive a copy of it. Patients should have “buy in,” meaning that they have had an opportunity to provide input to the contract and have agreed to its elements. Both the physician and patient should sign the document.

When all else fails

When there is a breakdown in rapport that makes it difficult or impossible to continue offering treatment, consider termination. This could be due to threatening or abusive patient behavior, sexual advances, repeated no-shows, treatment noncompliance that jeopardizes patient safety, refusal to follow the treatment plan, or violating the terms of a behavioral contract. In some settings, it might be the failure to pay bills.

Continue to: If a patient is unable to...

If a patient is unable to follow the contract, the physician should explore possible extenuating circumstances. The physician should seek to remedy the problem and involve other team members if possible (eg, case manager, nurse), advising a patient about behaviors that could lead to termination.

If the problem is irremediable, notify the patient in writing, give them time to find another physician, and facilitate the transfer of care.¹⁵ Take steps to prevent the patient from running out of any medications associated with withdrawal or discontinuation syndromes (eg, selective serotonin reuptake inhibitors, benzodiazepines) during the care transition. While there is no requirement regarding the amount of time allowed, at least 30 days is typical.

Bottom Line

Difficult patient interactions are common and unavoidable. Physicians should acknowledge and recognize contributing factors in such encounters—including their own role. When handling such situations, physicians should remain calm and model appropriate behavior. Improving communication, offering empathy, and validating the patient’s concerns can help resolve factors that contribute to poor patient interactions. If efforts to remediate the physician-patient relationship fail, termination may be necessary.

Related Resources

• Koekkoek B, Berno van Meijel CNS, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57(6):795-802.
• Pereira MR, Figueiredo AF. Challenging patient-doctor interactions in psychiatry – difficult patient syndrome. European Psychiatry. 2017;41(supplement):S719. doi. org/10.1016/j.eurpsy.2017.01.1297

DSM-5 defines personality disorders (PDs) as the presence of an enduring pattern of inner experience and behavior that “deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adulthood, is stable over time, and leads to distress or impairment.”¹ As a general rule, PDs are not limited to episodes of illness, but reflect an individual’s long-term adjustment. These disorders occur in 10% to 15% of the general population; the rates are especially high in health care settings, in criminal offenders, and in those with a substance use disorder (SUD).² PDs nearly always have an onset in adolescence or early adulthood and tend to diminish in severity with advancing age. They are associated with high rates of unemployment, homelessness, divorce and separation, domestic violence, substance misuse, and suicide.³

Psychotherapy is the first-line treatment for PDs, but there has been growing interest in using pharmacotherapy to treat PDs. While much of the PD treatment literature focuses on borderline PD,^4-9 this article describes diagnosis, potential pharmacotherapy strategies, and methods to assess response to treatment for patients with all types of PDs.

Recognizing and diagnosing personality disorders

The diagnosis of a PD requires an understanding of DSM-5 criteria combined with a comprehensive psychiatric history and mental status examination. The patient’s history is the most important basis for diagnosing a PD.² Collateral information from relatives or friends can help confirm the severity and pervasiveness of the individual’s personality problems. In some patients, long-term observation might be necessary to confirm the presence of a PD. Some clinicians are reluctant to diagnose PDs because of stigma, a problem common among patients with borderline PD.^10,11

To screen for PDs, a clinician might ask the patient about problems with interpersonal relationships, sense of self, work, affect, impulse control, and reality testing. Table 1¹² lists general screening questions for the presence of a PD from the Iowa Personality Disorders Screen. Structured diagnostic interviews and self-report assessments could boost recognition of PDs, but these tools are rarely used outside of research settings.^13,14

The PD clusters

DSM-5 divides 10 PDs into 3 clusters based on shared phenomenology and diagnostic criteria. Few patients have a “pure” case in which they meet criteria for only a single personality disorder.¹

Cluster A. “Eccentric cluster” disorders are united by social aversion, a failure to form close attachments, or paranoia and suspiciousness.¹⁵ These include paranoid, schizoid, and schizotypal PD. Low self-awareness is typical. There are no treatment guidelines for these disorders, although there is some clinical trial data for schizotypal PD.

Cluster B. “Dramatic cluster” disorders share dramatic, emotional, and erratic characteristics.¹⁴ These include narcissistic, antisocial, borderline, and histrionic PD. Antisocial and narcissistic patients have low self-awareness. There are treatment guidelines for antisocial and borderline PD, and a variety of clinical trial data is available for the latter.¹⁵

Continue to: Cluster C

Cluster C. “Anxious cluster” disorders are united by anxiousness, fearfulness, and poor self-esteem. Many of these patients also display interpersonal rigidity.¹⁵ These disorders include avoidant, dependent, and obsessive-compulsive PD. There are no treatment guidelines or clinical trial data for these disorders.

Why consider pharmacotherapy for personality disorders?

The consensus among experts is that psychotherapy is the treatment of choice for PDs.¹⁵ Despite significant gaps in the evidence base, there has been a growing interest in using psychotropic medication to treat PDs. For example, research shows that >90% of patients with borderline PD are prescribed medication, most typically antidepressants, antipsychotics, mood stabilizers, stimulants, or sedative-hypnotics.^16,17

Increased interest in pharmacotherapy for PDs could be related to research showing the importance of underlying neurobiology, particularly for antisocial and borderline PD.^18,19 This work is complemented by genetic research showing the heritability of PD traits and disorders.^20,21 Another factor could be renewed interest in dimensional approaches to the classification of PDs, as exemplified by DSM-5’s alternative model for PDs.¹ This approach aligns with some expert recommendations to focus on treating PD symptom dimensions, rather than the syndrome itself.²²

Importantly, no psychotropic medication is FDA-approved for the treatment of any PD. For that reason, prescribing medication for a PD is “off-label,” although prescribing a medication for a comorbid disorder for which the drug has an FDA-approved indication is not (eg, prescribing an antidepressant for major depressive disorder [MDD]).

Principles for prescribing

Despite gaps in research data, general principles for using medication to treat PDs have emerged from treatment guidelines for antisocial and borderline PD, clinical trial data, reviews and meta-analyses, and expert opinion. Clinicians should address the following considerations before prescribing medication to a patient with a PD.

Continue to: PD diagnosis

PD diagnosis. Has the patient been properly assessed and diagnosed? While history is the most important basis for diagnosis, the clinician should be familiar with the PDs and DSM-5 criteria. Has the patient been informed of the diagnosis and its implications for treatment?

Patient interest in medication. Is the patient interested in taking medication? Patients with borderline PD are often prescribed medication, but there are sparse data for the other PDs. The patient might have little interest in the PD diagnosis or its treatment.

Comorbidity. Has the patient been assessed for comorbid psychiatric disorders that could interfere with medication use (ie, an SUD) or might be a focus of treatment (eg, MDD)? Patients with PDs typically have significant comorbidity that a thorough evaluation will uncover.

PD symptom dimensions. Has the patient been assessed to determine cognitive or behavioral symptom dimensions of their PD? One or more symptom dimension(s) could be the focus of treatment. Table 2 lists examples of PD symptom dimensions.

Strategies to guide prescribing

Strategies to help guide prescribing include targeting any comorbid disorder(s), targeting important PD symptom dimensions (eg, impulsive aggression), choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself.

Continue to: Targeting comorbid disorders

Targeting comorbid disorders. National Institute for Health and Care Excellence guidelines for antisocial and borderline PD recommend that clinicians focus on treating comorbid disorders, a position echoed in Cochrane and other reviews.^4,9,22-26 For example, a patient with borderline PD experiencing a major depressive episode could be treated with an antidepressant. Targeting the depressive symptoms could boost the patient’s mood, perhaps lessening the individual’s PD symptoms or reducing their severity.

Targeting important symptom dimensions. For patients with borderline PD, several guidelines and reviews have suggested that treatment should focus on emotional dysregulation and impulsive aggression (mood stabilizers, antipsychotics), or cognitive-perceptual symptoms (antipsychotics).^4-6,15 There is some evidence that mood stabilizers or second-generation antipsychotics could help reduce impulsive aggression in patients with antisocial PD.²⁷

Choosing medication based on similarity to another disorder known to respond to medication. Avoidant PD overlaps with social anxiety disorder and can be conceptualized as a chronic, pervasive social phobia. Avoidant PD might respond to a medication known to be effective for treating social anxiety disorder, such as a selective serotonin reuptake inhibitor (SSRI) or venlafaxine.²⁸ Treating obsessive-compulsive PD with an SSRI is another example of this strategy, as 1 small study of fluvoxamine suggests.²⁹ Obsessive-compulsive PD is common in persons with obsessive-compulsive disorder, and overlap includes preoccupation with orders, rules, and lists, and an inability to throw things out.

Targeting the PD syndrome. Another strategy is to target the PD itself. Clinical trial data suggest the antipsychotic risperidone can reduce the symptoms of schizotypal PD.³⁰ Considering that this PD has a genetic association with schizophrenia, it is not surprising that the patient’s ideas of reference, odd communication, or transient paranoia might respond to an antipsychotic. Data from randomized controlled trials (RCTs) support the use of the second-generation antipsychotics aripiprazole and quetiapine to treat BPD.^31,32 While older guidelines^4,5 supported the use of the mood stabilizer lamotrigine, a recent RCT found that it was no more effective than placebo for borderline PD or its symptom dimensions.³³

What to do before prescribing

Before writing a prescription, the clinician and patient should discuss the presence of a PD and the desirability of treatment. The patient should understand the limited evidence base and know that medication prescribed for a PD is off-label. The clinician should discuss medication selection and its rationale, and whether the medication is targeting a comorbid disorder, symptom dimension(s), or the PD itself. Additional considerations for prescribing for patients with PDs are listed in Table 3.³⁴

Continue to: Avoid polypharmacy

Avoid polypharmacy. Many patients with borderline PD are prescribed multiple psychotropic medications.^16,17 This approach leads to greater expense and more adverse effects, and is not evidence-based.

Avoid benzodiazepines. Many patients with borderline PD are prescribed benzodiazepines, often as part of a polypharmacy regimen. These drugs can cause disinhibition, thereby increasing acting-out behaviors and self-harm.³⁵ Also, patients with PDs often have SUDs, which is a contraindication for benzodiazepine use.

Rate the patient’s improvement. Both the patient and clinician can benefit from monitoring symptomatic improvement. Several validated scales can be used to rate depression, anxiety, impulsivity, mood lability, anger, and aggression (Table 4^36-41).Some validated scales for borderline PD align with DSM-5 criteria. Two such widely used instruments are the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)⁴² and the self-rated Borderline Evaluation of Severity Over Time (BEST).⁴³ Each has questions that could be pulled to rate a symptom dimension of interest, such as affective instability, anger dyscontrol, or abandonment fears (Table 5^42,43).

A visual analog scale is easy to use and can target symptom dimensions of interest.⁴⁴ For example, a clinician could use a visual analog scale to rate mood instability by asking a patient to rate their mood severity by making a mark along a 10-cm line (0 = “Most erratic emotions I have experienced,” 10 = “Most stable I have ever experienced my emotions to be”). This score can be recorded at baseline and subsequent visits.

Take-home points

PDs are common in the general population and health care settings. They are underrecognized by the general public and mental health professionals, often because of stigma. Clinicians could boost their recognition of these disorders by embedding simple screening questions in their patient assessments. Many patients with PDs will be interested in pharmacotherapy for their disorder or symptoms. Treatment strategies include targeting the comorbid disorder(s), targeting important PD symptom dimensions, choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself. Each strategy has its limitations and varying degrees of empirical support. Treatment response can be monitored using validated scales or a visual analog scale.

Continue to: Bottom Line

Bottom Line

Although psychotherapy is the first-line treatment and no medications are FDAapproved for treating personality disorders (PDs), there has been growing interest in using psychotropic medication to treat PDs. Strategies for pharmacotherapy include targeting comorbid disorders, PD symptom dimensions, or the PD itself. Choice of medication can be based on the similarity of the PD with another disorder known to respond to medication.

Related Resources

• Correa Da Costa S, Sanches M, Soares JC. Bipolar disorder or borderline personality disorder? Current Psychiatry. 2019;18(11):26-29,35-39.
• Bateman A, Gunderson J, Mulder R. Treatment of personality disorders. Lancet. 2015;385(9969):735-743.

Drug Brand Names

Aripiprazole • Abilify
Fluvoxamine • Luvox
Lamotrigine • Lamictal
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor

DSM-5 defines personality disorders (PDs) as the presence of an enduring pattern of inner experience and behavior that “deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adulthood, is stable over time, and leads to distress or impairment.”¹ As a general rule, PDs are not limited to episodes of illness, but reflect an individual’s long-term adjustment. These disorders occur in 10% to 15% of the general population; the rates are especially high in health care settings, in criminal offenders, and in those with a substance use disorder (SUD).² PDs nearly always have an onset in adolescence or early adulthood and tend to diminish in severity with advancing age. They are associated with high rates of unemployment, homelessness, divorce and separation, domestic violence, substance misuse, and suicide.³

Psychotherapy is the first-line treatment for PDs, but there has been growing interest in using pharmacotherapy to treat PDs. While much of the PD treatment literature focuses on borderline PD,^4-9 this article describes diagnosis, potential pharmacotherapy strategies, and methods to assess response to treatment for patients with all types of PDs.

Recognizing and diagnosing personality disorders

The diagnosis of a PD requires an understanding of DSM-5 criteria combined with a comprehensive psychiatric history and mental status examination. The patient’s history is the most important basis for diagnosing a PD.² Collateral information from relatives or friends can help confirm the severity and pervasiveness of the individual’s personality problems. In some patients, long-term observation might be necessary to confirm the presence of a PD. Some clinicians are reluctant to diagnose PDs because of stigma, a problem common among patients with borderline PD.^10,11

To screen for PDs, a clinician might ask the patient about problems with interpersonal relationships, sense of self, work, affect, impulse control, and reality testing. Table 1¹² lists general screening questions for the presence of a PD from the Iowa Personality Disorders Screen. Structured diagnostic interviews and self-report assessments could boost recognition of PDs, but these tools are rarely used outside of research settings.^13,14

The PD clusters

DSM-5 divides 10 PDs into 3 clusters based on shared phenomenology and diagnostic criteria. Few patients have a “pure” case in which they meet criteria for only a single personality disorder.¹

Cluster A. “Eccentric cluster” disorders are united by social aversion, a failure to form close attachments, or paranoia and suspiciousness.¹⁵ These include paranoid, schizoid, and schizotypal PD. Low self-awareness is typical. There are no treatment guidelines for these disorders, although there is some clinical trial data for schizotypal PD.

Cluster B. “Dramatic cluster” disorders share dramatic, emotional, and erratic characteristics.¹⁴ These include narcissistic, antisocial, borderline, and histrionic PD. Antisocial and narcissistic patients have low self-awareness. There are treatment guidelines for antisocial and borderline PD, and a variety of clinical trial data is available for the latter.¹⁵

Continue to: Cluster C

Cluster C. “Anxious cluster” disorders are united by anxiousness, fearfulness, and poor self-esteem. Many of these patients also display interpersonal rigidity.¹⁵ These disorders include avoidant, dependent, and obsessive-compulsive PD. There are no treatment guidelines or clinical trial data for these disorders.

Why consider pharmacotherapy for personality disorders?

The consensus among experts is that psychotherapy is the treatment of choice for PDs.¹⁵ Despite significant gaps in the evidence base, there has been a growing interest in using psychotropic medication to treat PDs. For example, research shows that >90% of patients with borderline PD are prescribed medication, most typically antidepressants, antipsychotics, mood stabilizers, stimulants, or sedative-hypnotics.^16,17

Increased interest in pharmacotherapy for PDs could be related to research showing the importance of underlying neurobiology, particularly for antisocial and borderline PD.^18,19 This work is complemented by genetic research showing the heritability of PD traits and disorders.^20,21 Another factor could be renewed interest in dimensional approaches to the classification of PDs, as exemplified by DSM-5’s alternative model for PDs.¹ This approach aligns with some expert recommendations to focus on treating PD symptom dimensions, rather than the syndrome itself.²²

Importantly, no psychotropic medication is FDA-approved for the treatment of any PD. For that reason, prescribing medication for a PD is “off-label,” although prescribing a medication for a comorbid disorder for which the drug has an FDA-approved indication is not (eg, prescribing an antidepressant for major depressive disorder [MDD]).

Principles for prescribing

Despite gaps in research data, general principles for using medication to treat PDs have emerged from treatment guidelines for antisocial and borderline PD, clinical trial data, reviews and meta-analyses, and expert opinion. Clinicians should address the following considerations before prescribing medication to a patient with a PD.

Continue to: PD diagnosis

PD diagnosis. Has the patient been properly assessed and diagnosed? While history is the most important basis for diagnosis, the clinician should be familiar with the PDs and DSM-5 criteria. Has the patient been informed of the diagnosis and its implications for treatment?

Patient interest in medication. Is the patient interested in taking medication? Patients with borderline PD are often prescribed medication, but there are sparse data for the other PDs. The patient might have little interest in the PD diagnosis or its treatment.

Comorbidity. Has the patient been assessed for comorbid psychiatric disorders that could interfere with medication use (ie, an SUD) or might be a focus of treatment (eg, MDD)? Patients with PDs typically have significant comorbidity that a thorough evaluation will uncover.

PD symptom dimensions. Has the patient been assessed to determine cognitive or behavioral symptom dimensions of their PD? One or more symptom dimension(s) could be the focus of treatment. Table 2 lists examples of PD symptom dimensions.

Strategies to guide prescribing

Strategies to help guide prescribing include targeting any comorbid disorder(s), targeting important PD symptom dimensions (eg, impulsive aggression), choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself.

Continue to: Targeting comorbid disorders

Targeting comorbid disorders. National Institute for Health and Care Excellence guidelines for antisocial and borderline PD recommend that clinicians focus on treating comorbid disorders, a position echoed in Cochrane and other reviews.^4,9,22-26 For example, a patient with borderline PD experiencing a major depressive episode could be treated with an antidepressant. Targeting the depressive symptoms could boost the patient’s mood, perhaps lessening the individual’s PD symptoms or reducing their severity.

Targeting important symptom dimensions. For patients with borderline PD, several guidelines and reviews have suggested that treatment should focus on emotional dysregulation and impulsive aggression (mood stabilizers, antipsychotics), or cognitive-perceptual symptoms (antipsychotics).^4-6,15 There is some evidence that mood stabilizers or second-generation antipsychotics could help reduce impulsive aggression in patients with antisocial PD.²⁷

Choosing medication based on similarity to another disorder known to respond to medication. Avoidant PD overlaps with social anxiety disorder and can be conceptualized as a chronic, pervasive social phobia. Avoidant PD might respond to a medication known to be effective for treating social anxiety disorder, such as a selective serotonin reuptake inhibitor (SSRI) or venlafaxine.²⁸ Treating obsessive-compulsive PD with an SSRI is another example of this strategy, as 1 small study of fluvoxamine suggests.²⁹ Obsessive-compulsive PD is common in persons with obsessive-compulsive disorder, and overlap includes preoccupation with orders, rules, and lists, and an inability to throw things out.

Targeting the PD syndrome. Another strategy is to target the PD itself. Clinical trial data suggest the antipsychotic risperidone can reduce the symptoms of schizotypal PD.³⁰ Considering that this PD has a genetic association with schizophrenia, it is not surprising that the patient’s ideas of reference, odd communication, or transient paranoia might respond to an antipsychotic. Data from randomized controlled trials (RCTs) support the use of the second-generation antipsychotics aripiprazole and quetiapine to treat BPD.^31,32 While older guidelines^4,5 supported the use of the mood stabilizer lamotrigine, a recent RCT found that it was no more effective than placebo for borderline PD or its symptom dimensions.³³

What to do before prescribing

Before writing a prescription, the clinician and patient should discuss the presence of a PD and the desirability of treatment. The patient should understand the limited evidence base and know that medication prescribed for a PD is off-label. The clinician should discuss medication selection and its rationale, and whether the medication is targeting a comorbid disorder, symptom dimension(s), or the PD itself. Additional considerations for prescribing for patients with PDs are listed in Table 3.³⁴

Continue to: Avoid polypharmacy

Avoid polypharmacy. Many patients with borderline PD are prescribed multiple psychotropic medications.^16,17 This approach leads to greater expense and more adverse effects, and is not evidence-based.

Avoid benzodiazepines. Many patients with borderline PD are prescribed benzodiazepines, often as part of a polypharmacy regimen. These drugs can cause disinhibition, thereby increasing acting-out behaviors and self-harm.³⁵ Also, patients with PDs often have SUDs, which is a contraindication for benzodiazepine use.

Rate the patient’s improvement. Both the patient and clinician can benefit from monitoring symptomatic improvement. Several validated scales can be used to rate depression, anxiety, impulsivity, mood lability, anger, and aggression (Table 4^36-41).Some validated scales for borderline PD align with DSM-5 criteria. Two such widely used instruments are the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)⁴² and the self-rated Borderline Evaluation of Severity Over Time (BEST).⁴³ Each has questions that could be pulled to rate a symptom dimension of interest, such as affective instability, anger dyscontrol, or abandonment fears (Table 5^42,43).

A visual analog scale is easy to use and can target symptom dimensions of interest.⁴⁴ For example, a clinician could use a visual analog scale to rate mood instability by asking a patient to rate their mood severity by making a mark along a 10-cm line (0 = “Most erratic emotions I have experienced,” 10 = “Most stable I have ever experienced my emotions to be”). This score can be recorded at baseline and subsequent visits.

Take-home points

PDs are common in the general population and health care settings. They are underrecognized by the general public and mental health professionals, often because of stigma. Clinicians could boost their recognition of these disorders by embedding simple screening questions in their patient assessments. Many patients with PDs will be interested in pharmacotherapy for their disorder or symptoms. Treatment strategies include targeting the comorbid disorder(s), targeting important PD symptom dimensions, choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself. Each strategy has its limitations and varying degrees of empirical support. Treatment response can be monitored using validated scales or a visual analog scale.

Continue to: Bottom Line

Bottom Line

Although psychotherapy is the first-line treatment and no medications are FDAapproved for treating personality disorders (PDs), there has been growing interest in using psychotropic medication to treat PDs. Strategies for pharmacotherapy include targeting comorbid disorders, PD symptom dimensions, or the PD itself. Choice of medication can be based on the similarity of the PD with another disorder known to respond to medication.

Related Resources

• Correa Da Costa S, Sanches M, Soares JC. Bipolar disorder or borderline personality disorder? Current Psychiatry. 2019;18(11):26-29,35-39.
• Bateman A, Gunderson J, Mulder R. Treatment of personality disorders. Lancet. 2015;385(9969):735-743.

Drug Brand Names

Aripiprazole • Abilify
Fluvoxamine • Luvox
Lamotrigine • Lamictal
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor

DSM-5 defines personality disorders (PDs) as the presence of an enduring pattern of inner experience and behavior that “deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adulthood, is stable over time, and leads to distress or impairment.”¹ As a general rule, PDs are not limited to episodes of illness, but reflect an individual’s long-term adjustment. These disorders occur in 10% to 15% of the general population; the rates are especially high in health care settings, in criminal offenders, and in those with a substance use disorder (SUD).² PDs nearly always have an onset in adolescence or early adulthood and tend to diminish in severity with advancing age. They are associated with high rates of unemployment, homelessness, divorce and separation, domestic violence, substance misuse, and suicide.³

Psychotherapy is the first-line treatment for PDs, but there has been growing interest in using pharmacotherapy to treat PDs. While much of the PD treatment literature focuses on borderline PD,^4-9 this article describes diagnosis, potential pharmacotherapy strategies, and methods to assess response to treatment for patients with all types of PDs.

Recognizing and diagnosing personality disorders

The diagnosis of a PD requires an understanding of DSM-5 criteria combined with a comprehensive psychiatric history and mental status examination. The patient’s history is the most important basis for diagnosing a PD.² Collateral information from relatives or friends can help confirm the severity and pervasiveness of the individual’s personality problems. In some patients, long-term observation might be necessary to confirm the presence of a PD. Some clinicians are reluctant to diagnose PDs because of stigma, a problem common among patients with borderline PD.^10,11

To screen for PDs, a clinician might ask the patient about problems with interpersonal relationships, sense of self, work, affect, impulse control, and reality testing. Table 1¹² lists general screening questions for the presence of a PD from the Iowa Personality Disorders Screen. Structured diagnostic interviews and self-report assessments could boost recognition of PDs, but these tools are rarely used outside of research settings.^13,14

The PD clusters

DSM-5 divides 10 PDs into 3 clusters based on shared phenomenology and diagnostic criteria. Few patients have a “pure” case in which they meet criteria for only a single personality disorder.¹

Cluster A. “Eccentric cluster” disorders are united by social aversion, a failure to form close attachments, or paranoia and suspiciousness.¹⁵ These include paranoid, schizoid, and schizotypal PD. Low self-awareness is typical. There are no treatment guidelines for these disorders, although there is some clinical trial data for schizotypal PD.

Cluster B. “Dramatic cluster” disorders share dramatic, emotional, and erratic characteristics.¹⁴ These include narcissistic, antisocial, borderline, and histrionic PD. Antisocial and narcissistic patients have low self-awareness. There are treatment guidelines for antisocial and borderline PD, and a variety of clinical trial data is available for the latter.¹⁵

Continue to: Cluster C

Cluster C. “Anxious cluster” disorders are united by anxiousness, fearfulness, and poor self-esteem. Many of these patients also display interpersonal rigidity.¹⁵ These disorders include avoidant, dependent, and obsessive-compulsive PD. There are no treatment guidelines or clinical trial data for these disorders.

Why consider pharmacotherapy for personality disorders?

The consensus among experts is that psychotherapy is the treatment of choice for PDs.¹⁵ Despite significant gaps in the evidence base, there has been a growing interest in using psychotropic medication to treat PDs. For example, research shows that >90% of patients with borderline PD are prescribed medication, most typically antidepressants, antipsychotics, mood stabilizers, stimulants, or sedative-hypnotics.^16,17

Increased interest in pharmacotherapy for PDs could be related to research showing the importance of underlying neurobiology, particularly for antisocial and borderline PD.^18,19 This work is complemented by genetic research showing the heritability of PD traits and disorders.^20,21 Another factor could be renewed interest in dimensional approaches to the classification of PDs, as exemplified by DSM-5’s alternative model for PDs.¹ This approach aligns with some expert recommendations to focus on treating PD symptom dimensions, rather than the syndrome itself.²²

Importantly, no psychotropic medication is FDA-approved for the treatment of any PD. For that reason, prescribing medication for a PD is “off-label,” although prescribing a medication for a comorbid disorder for which the drug has an FDA-approved indication is not (eg, prescribing an antidepressant for major depressive disorder [MDD]).

Principles for prescribing

Despite gaps in research data, general principles for using medication to treat PDs have emerged from treatment guidelines for antisocial and borderline PD, clinical trial data, reviews and meta-analyses, and expert opinion. Clinicians should address the following considerations before prescribing medication to a patient with a PD.

Continue to: PD diagnosis

PD diagnosis. Has the patient been properly assessed and diagnosed? While history is the most important basis for diagnosis, the clinician should be familiar with the PDs and DSM-5 criteria. Has the patient been informed of the diagnosis and its implications for treatment?

Patient interest in medication. Is the patient interested in taking medication? Patients with borderline PD are often prescribed medication, but there are sparse data for the other PDs. The patient might have little interest in the PD diagnosis or its treatment.

Comorbidity. Has the patient been assessed for comorbid psychiatric disorders that could interfere with medication use (ie, an SUD) or might be a focus of treatment (eg, MDD)? Patients with PDs typically have significant comorbidity that a thorough evaluation will uncover.

PD symptom dimensions. Has the patient been assessed to determine cognitive or behavioral symptom dimensions of their PD? One or more symptom dimension(s) could be the focus of treatment. Table 2 lists examples of PD symptom dimensions.

Strategies to guide prescribing

Strategies to help guide prescribing include targeting any comorbid disorder(s), targeting important PD symptom dimensions (eg, impulsive aggression), choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself.

Continue to: Targeting comorbid disorders

Targeting comorbid disorders. National Institute for Health and Care Excellence guidelines for antisocial and borderline PD recommend that clinicians focus on treating comorbid disorders, a position echoed in Cochrane and other reviews.^4,9,22-26 For example, a patient with borderline PD experiencing a major depressive episode could be treated with an antidepressant. Targeting the depressive symptoms could boost the patient’s mood, perhaps lessening the individual’s PD symptoms or reducing their severity.

Targeting important symptom dimensions. For patients with borderline PD, several guidelines and reviews have suggested that treatment should focus on emotional dysregulation and impulsive aggression (mood stabilizers, antipsychotics), or cognitive-perceptual symptoms (antipsychotics).^4-6,15 There is some evidence that mood stabilizers or second-generation antipsychotics could help reduce impulsive aggression in patients with antisocial PD.²⁷

Choosing medication based on similarity to another disorder known to respond to medication. Avoidant PD overlaps with social anxiety disorder and can be conceptualized as a chronic, pervasive social phobia. Avoidant PD might respond to a medication known to be effective for treating social anxiety disorder, such as a selective serotonin reuptake inhibitor (SSRI) or venlafaxine.²⁸ Treating obsessive-compulsive PD with an SSRI is another example of this strategy, as 1 small study of fluvoxamine suggests.²⁹ Obsessive-compulsive PD is common in persons with obsessive-compulsive disorder, and overlap includes preoccupation with orders, rules, and lists, and an inability to throw things out.

Targeting the PD syndrome. Another strategy is to target the PD itself. Clinical trial data suggest the antipsychotic risperidone can reduce the symptoms of schizotypal PD.³⁰ Considering that this PD has a genetic association with schizophrenia, it is not surprising that the patient’s ideas of reference, odd communication, or transient paranoia might respond to an antipsychotic. Data from randomized controlled trials (RCTs) support the use of the second-generation antipsychotics aripiprazole and quetiapine to treat BPD.^31,32 While older guidelines^4,5 supported the use of the mood stabilizer lamotrigine, a recent RCT found that it was no more effective than placebo for borderline PD or its symptom dimensions.³³

What to do before prescribing

Before writing a prescription, the clinician and patient should discuss the presence of a PD and the desirability of treatment. The patient should understand the limited evidence base and know that medication prescribed for a PD is off-label. The clinician should discuss medication selection and its rationale, and whether the medication is targeting a comorbid disorder, symptom dimension(s), or the PD itself. Additional considerations for prescribing for patients with PDs are listed in Table 3.³⁴

Continue to: Avoid polypharmacy

Avoid polypharmacy. Many patients with borderline PD are prescribed multiple psychotropic medications.^16,17 This approach leads to greater expense and more adverse effects, and is not evidence-based.

Avoid benzodiazepines. Many patients with borderline PD are prescribed benzodiazepines, often as part of a polypharmacy regimen. These drugs can cause disinhibition, thereby increasing acting-out behaviors and self-harm.³⁵ Also, patients with PDs often have SUDs, which is a contraindication for benzodiazepine use.

Rate the patient’s improvement. Both the patient and clinician can benefit from monitoring symptomatic improvement. Several validated scales can be used to rate depression, anxiety, impulsivity, mood lability, anger, and aggression (Table 4^36-41).Some validated scales for borderline PD align with DSM-5 criteria. Two such widely used instruments are the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)⁴² and the self-rated Borderline Evaluation of Severity Over Time (BEST).⁴³ Each has questions that could be pulled to rate a symptom dimension of interest, such as affective instability, anger dyscontrol, or abandonment fears (Table 5^42,43).

A visual analog scale is easy to use and can target symptom dimensions of interest.⁴⁴ For example, a clinician could use a visual analog scale to rate mood instability by asking a patient to rate their mood severity by making a mark along a 10-cm line (0 = “Most erratic emotions I have experienced,” 10 = “Most stable I have ever experienced my emotions to be”). This score can be recorded at baseline and subsequent visits.

Take-home points

PDs are common in the general population and health care settings. They are underrecognized by the general public and mental health professionals, often because of stigma. Clinicians could boost their recognition of these disorders by embedding simple screening questions in their patient assessments. Many patients with PDs will be interested in pharmacotherapy for their disorder or symptoms. Treatment strategies include targeting the comorbid disorder(s), targeting important PD symptom dimensions, choosing medication based on the similarity of the PD to another disorder known to respond to medication, and targeting the PD itself. Each strategy has its limitations and varying degrees of empirical support. Treatment response can be monitored using validated scales or a visual analog scale.

Continue to: Bottom Line

Bottom Line

Although psychotherapy is the first-line treatment and no medications are FDAapproved for treating personality disorders (PDs), there has been growing interest in using psychotropic medication to treat PDs. Strategies for pharmacotherapy include targeting comorbid disorders, PD symptom dimensions, or the PD itself. Choice of medication can be based on the similarity of the PD with another disorder known to respond to medication.

Related Resources

• Correa Da Costa S, Sanches M, Soares JC. Bipolar disorder or borderline personality disorder? Current Psychiatry. 2019;18(11):26-29,35-39.
• Bateman A, Gunderson J, Mulder R. Treatment of personality disorders. Lancet. 2015;385(9969):735-743.

Drug Brand Names

Aripiprazole • Abilify
Fluvoxamine • Luvox
Lamotrigine • Lamictal
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal

The negative symptoms of schizophrenia have been recognized for 100 years. Characterized by a loss of a function that should be present, negative symptoms include anhedonia, asociality, amotivation, and affective blunting. Individuals with schizophrenia who have a preponderance of negative symptoms (“deficit syndrome”) may comprise a special subset of patients. Compared with positive symptoms, negative symptoms are associated with worse global functioning and worse response to antipsychotic medication. Treatment of negative symptoms is challenging. Secondary negative symptoms—those that simulate or resemble primary negative symptoms but are attributable to another cause, such as major depressive disorder or the adverse effects of antipsychotic medication—need to be ruled out. Emerging evidence suggests that newer antipsychotics with novel mechanisms might be effective in treating negative symptoms. Antidepressants might also play a role.

This article describes types of negative symptoms, their clinical relevance, neuroanatomical and neurotransmission factors associated with negative symptoms, and current and future treatment options.

Modest improvements with antipsychotics

Schizophrenia affects an estimated 1% of the population.¹ Antipsychotic medication has been the mainstay of schizophrenia treatment since chlorpromazine was introduced in the 1950s; it was soon followed by many other antipsychotics. These first-generation antipsychotics (FGAs) were joined by second-generation antipsychotics (SGAs) in the 1990s. While SGAs are better tolerated and less likely to induce extrapyramidal side effects (EPS) than FGAs, they also are associated with troubling metabolic adverse effects (eg, impaired glucose tolerance).¹

All antipsychotics are believed to exert their therapeutic effects by blocking dopamine (D2) receptors and are effective in ameliorating the positive symptoms of schizophrenia, including hallucinations, delusions, bizarre behavior, disordered thinking, and agitation.¹ Early research had suggested that SGAs might also reduce the negative symptoms of schizophrenia, perhaps because they also block serotonin 2A receptors, a property thought to broaden their therapeutic profile. Over time, it became clear that neither FGAs nor SGAs conferred an advantage in treating negative symptoms, and that the observed improvements were modest.^2-5 However, recent research suggests that several newer antipsychotics might be effective in targeting negative symptoms.^2,6,7

History of negative symptoms

In the early 20th century, Swiss psychiatrist Eugen Bleuler coined the term schizophrenia to emphasize the cognitive impairment that occurs in patients with this illness, and which he conceptualized as a fragmenting of the psychic process.⁸ He believed that certain symptoms were fundamental to the illness, and described affective blunting, disturbance of association (ie, distorted thinking) autism (ie, impaired relationships), and ambivalence (ie, fragmented emotional responses). He viewed hallucinations and delusions as accessory symptoms because they were not unique to schizophrenia but were also found in other disorders (eg, mood disorders). Bleuler’s ideas took root, and generations of psychiatrists were taught his fundamental symptoms (“the 4 A’s”), the forerunner of today’s negative symptoms. Later, other experts chose to emphasize psychotic symptoms as most characteristic of schizophrenia, including Schneider’s “first-rank symptoms,” such as voices conversing or delusions of passivity.⁹

Negative symptoms were rediscovered in the 1970s and 1980s by psychiatric researchers interested in descriptive phenomenology.^10,11 Research confirmed the presence of a positive dimension in schizophrenia characterized by the loss of boundaries between the patient and the real world (eg, hallucinations, delusions), and a negative dimension characterized by the loss of a function that should be present, such as alogia and asociality. These experts carefully described negative symptoms and created scales to measure them, including the Scale for the Assessment of Negative Symptoms (SANS),¹² the Positive and Negative Syndrome Scale (PANSS),¹³ the Brief Negative Symptom Scale (BNSS),¹⁴ and the 16-item Negative Symptom Assessment (NSA-16).¹⁵ Contemporaneous to this work, a “deficit syndrome” was identified among patients with schizophrenia with prominent negative symptoms. The deficit syndrome is found in 25% to 30% of chronic cases.¹⁶ Negative symptoms are very common in patients with schizophrenia (Table 1⁹).^8,17

Early editions of the DSM defined schizophrenia mainly on the basis of disturbance of cognition, mood, and behavior, and a retreat from reality. With the publication of DSM-III in 1980, and in subsequent editions, schizophrenia was redefined as a relatively severe psychotic illness in which positive and negative symptoms were present, thereby acknowledging the importance of Bleuler’s fundamental symptoms. In DSM-5, negative symptoms are described as accounting for “a substantial portion of the morbidity associated with schizophrenia but are less prominent in other psychotic disorders.”¹⁸

Continue to: Types of negative symptoms

Types of negative symptoms

The following symptoms fall within the negative dimension¹⁹:

Alogia refers to the impoverished thinking and cognition that often occur in patients with schizophrenia. The patient’s thinking processes seem empty, turgid, or slow, as inferred from the patient’s speech. The 2 major manifestations of alogia are poverty of speech (nonfluent empty speech) and poverty of content of speech (fluent but empty speech). Examples of each appear in Table 2.¹⁹

Affective flattening or blunting manifests as a general impoverishment of emotional expression, reactivity, and feeling. Affective flattening can be assessed through observing a patient’s behavior and responsiveness during the interview.

Avolition-apathy manifests itself as a lack of energy and drive. Patients become inert and are unable to mobilize themselves to initiate or persist in completing many kinds of tasks.

Anhedonia-asociality encompasses the patient’s difficulties in experiencing interest or pleasure. It may express itself as a loss of interest in pleasurable activities, an inability to experience pleasure when participating in activities normally considered pleasurable, or a lack of involvement in social relationships.

Continue to: Attention

Attention is often poor in patients with severe mental illnesses. The patient may have trouble focusing his/her attention or may be able to focus only sporadically and erratically. He/she may ignore attempts to converse with him/her, wander away during an activity or a task, or appear to be inattentive when engaged in formal testing or interviewing.

Clinical relevance of negative symptoms

According to DSM-5, “Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent.”¹⁸ Research has shown that, compared with positive symptoms, negative symptoms are associated with greater impairment in overall functioning, social interaction, interpersonal relationships, economic functioning, and recreational activities.^1,3,5 Negative symptoms also are associated with poorer response to medication and a positive family history of schizophrenia. Research shows that negative symptoms are persistent over time, and, in fact, become more prominent as the patient ages, whereas positive symptoms become less prominent.²⁰

Secondary negative symptoms

Potential secondary causes of negative symptoms should be ruled out before concluding that the negative symptoms are due to schizophrenia.³ What might appear to be a negative symptom of schizophrenia, such as poor motivation or flattened affect, could be due to the presence of major depressive disorder. Such symptoms might resolve with treatment. Alternatively, a patient could have developed pseudoparkinsonism from antipsychotic medication and display unchanging facial expression and decreased spontaneous movements. These symptoms could resolve by adding benztropine or a similar medication to the treatment regimen. Other potential causes of secondary negative symptoms range from chronic substance abuse (eg, leading to poor grooming and hygiene), to paranoia and hallucinations, to sleep apnea inducing anergia and impersistence at work. Causes of secondary negative symptoms are outlined in Table 3.³

The neuroanatomy of negative symptoms

Although the neuroanatomical basis of negative symptoms has not been determined, neuroimaging studies have provided important clues.³ Structural brain imaging has consistently shown that negative symptoms in patients with schizophrenia correlate with decreased prefrontal white matter volume, anterior cingulate volume, insular cortex volume, left temporal cortex volume, and ventricular enlargement. Interestingly, volume loss starts before the appearance of negative symptoms.^21,22 Functional imaging has shown that negative symptoms correlate with reduced cerebral blood perfusion in frontal, prefrontal, posterior cingulate, thalamus, parietal, and striatal regions.^21,22 These findings may help explain the apathy, failure to initiate activities, and impaired social relatedness in patients with schizophrenia.

Neurotransmission and negative symptoms

Some experts have hypothesized that lowered cortical dopamine transmission in mesocortical pathways could give rise to negative symptoms, whereas excess transmission in subcortical structures leads to positive symptoms.²³ There is also evidence for a noradrenalin deficiency based on the finding that low levels of cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), a noradrenaline metabolite, correlates with greater negative symptom severity.²⁴ The presence of a serotonin deficiency has been proposed based on evidence that negative symptoms might be mitigated by serotonergic agents.²⁵ More recently, some experts have posited that the dopamine D3 receptor might be involved in the etiology of negative symptoms. The dopamine D3 receptor activity is expressed in brain regions thought to control reward, emotions, and motivation.² Newer medications with novel mechanisms suggest that other neuro­transmitter pathways could be involved.^6,7

Continue to: Treatment options

Treating negative symptoms remains challenging and there are no clear answers. When they were introduced in the 1990s, SGAs were initially thought to be superior to FGAs in targeting negative symptoms. Subsequent research, including recent reviews and meta-analyses, has shown that SGAs are not superior to FGAs in treating negative symptoms, and the effect of either medication class on negative symptoms is modest.^2-5 One exception is amisulpride (not available in the United States), which is known to antagonize D2 and D3 receptors. A meta-analysis of the efficacy of antipsychotics in schizophrenia showed that amisulpride was significantly more effective than placebo in treating negative symptoms in 590 patients who received the medication.²⁶ The authors suggested that amisulpride was effective due to its binding to presynaptic receptors in the frontal cortex, thereby enhancing dopamine transmission in this region.

Cariprazine, which acts as a partial agonist at the D2 and D3 receptors, with a 10-fold affinity for the D3 receptor, also has shown promise in treating negative symptoms.² In a clinical trial of 460 patients with predominant negative symptoms, treatment with cariprazine led to a greater reduction in negative symptoms than risperidone, although the effect size was small.²⁷ In this study, cariprazine produced greater improvement in personal and social performance than risperidone. Animal data supports the possible use of cariprazine in treating negative symptoms.²⁸

Other promising agentsinclude roluperidone (MIN-101), in phase 3 of development, and SEP-363856, an investigational antipsychotic agent that is in phase 2 of development. Interestingly, roluperidone acts on serotonin 2A and sigma2 receptors and does not target dopamine receptors, whereas SEP-363856 is thought to activate trace amine-associated receptor 1 (TAAR1) in addition to serotonin 1A receptors.^6,7

Antidepressants also could be effective in reducing negative symptoms.³ A meta-analysis of randomized controlled trials evaluating the use of antidepressants as adjuncts to antipsychotic medications showed that adding an antidepressant was effective in reducing negative symptoms.²⁹ The mechanism by which an antidepressant might cause a reduction in negative symptoms is uncertain, and it is possible that the antidepressant might treat depressive symptoms that are causing or contributing to the negative symptoms.

Bottom Line

Negative symptoms in patients with schizophrenia are associated with a worse functional outcome and poorer response to antipsychotic medication than positive symptoms. First- and second-generation antipsychotics are largely ineffective in consistently treating negative symptoms. Antipsychotic medications that target the D3 receptor might be more effective. Roluperidone, which targets serotonin 2A and sigma receptors, and SEP-363856, which targets TAAR1 and serotonin 1A receptors, are being studied for their effects on negative symptoms.

Continue to: Related Resources

• Galderisi S, Färden A, Kaiser S. Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. Schizophr Res. 2017;186:1-2.
• Rabinowitz J. Treating negative symptoms of schizophrenia. Current Psychiatry. 2018;17(12):19-23.

Drug Brand Names

Benztropine • Cogentin
Cariprazine • Vraylar
Chlorpromazine • Promapar, Thorazine
Risperidone • Risperdal

Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.

Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with olanzapine, 20 mg by mouth nightly, with moderate improvement in his symptoms, although he never fully returned to baseline.

Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.

In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.

Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.¹

SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.¹ In this review, we describe the classification of SAD and its features, diagnosis, and treatment.

An evolving diagnosis

The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.² He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.³ In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”³ Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.⁴ These criteria continued to evolve with subsequent editions of the DSM.

Continue to: DSM-5 provides...

DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table⁵). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.⁶ Despite improvements in classification, the diagnosis remains controversial (Box^7-11).

Box 1

DSM-5 subtypes and specifiers

In DSM-5,SAD has 2 subtypes⁵:

• Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
• Depressive type. The depressive type is marked by the presence of only major depressive episodes.

SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.

Epidemiology and gender ratio

The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.⁵ This is similar to an estimate by Perälä et al¹² of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al¹³ calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al¹⁴ estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al¹⁵ based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.

The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.^13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.⁵ The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.²⁰

Continue to: Course and outcome

The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.^21-23 Based on a literature review, Cheniaux et al⁷ concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.

The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,²⁴ patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.²⁵ Mood symptoms portend a better outcome than do symptoms of schizophrenia.

The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.²⁶ One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).²⁷

Comorbidity

Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.^21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.^27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.³⁰

Clinical assessment

Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.³¹ This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.

Continue to: Differential diagnosis

The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders⁵:

• schizophrenia
• bipolar disorder with psychotic features
• major depressive disorder with psychotic features
• depressive or bipolar disorders with catatonic features
• personality disorders (especially the schizotypal, paranoid, and borderline types)
• major neurocognitive disorders in which there are mood and psychotic symptoms
• substance/medication-induced psychotic disorder
• disorders induced by medical conditions.

With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.

Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.

Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.

Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.

Continue to: Clinical symptoms

The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.

Brain imaging

Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.^32-35 Amann et al³² found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.

Treatment of SAD

The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg, lithium, valproate) or an antidepressant, depending on the patient’s SAD subtype. Jäger et al³⁶ reviewed 33 treatment studies published up to 2007 that employed widely accepted diagnostic criteria and reported results for SAD patients. They concluded that mood stabilizers and antipsychotics appeared to be effective, but that it was not possible to provide treatment guidelines.

Since that exhaustive review, aripiprazole was compared with placebo in 2 separate trials that include patients with schizophrenia and patients with SAD.³⁷ In a pooled sub-analysis of SAD, aripiprazole was found to be more effective on some but not all measures, suggesting efficacy. Based on 2 randomized controlled trials, the FDA approved the use of paliperidone, an SGA, as monotherapy in the acute treatment of SAD and in combination with mood stabilizers and/or antidepressants.^38,39 It is likely that other SGAs are also effective.

Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.⁴⁰ The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.^41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.⁴³ One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.

Continue to: There is a single clinical trial...

There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to lurasidone, although this study had no long-term follow-up.⁴⁴

Other approaches

Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).⁴⁵

As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.

Bottom Line

Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.

Related Resources

• Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
• Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.

Drug Brand Names

Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon

Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.

Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with olanzapine, 20 mg by mouth nightly, with moderate improvement in his symptoms, although he never fully returned to baseline.

Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.

In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.

Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.¹

SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.¹ In this review, we describe the classification of SAD and its features, diagnosis, and treatment.

An evolving diagnosis

The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.² He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.³ In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”³ Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.⁴ These criteria continued to evolve with subsequent editions of the DSM.

Continue to: DSM-5 provides...

DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table⁵). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.⁶ Despite improvements in classification, the diagnosis remains controversial (Box^7-11).

Box 1

DSM-5 subtypes and specifiers

In DSM-5,SAD has 2 subtypes⁵:

• Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
• Depressive type. The depressive type is marked by the presence of only major depressive episodes.

SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.

Epidemiology and gender ratio

The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.⁵ This is similar to an estimate by Perälä et al¹² of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al¹³ calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al¹⁴ estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al¹⁵ based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.

The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.^13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.⁵ The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.²⁰

Continue to: Course and outcome

The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.^21-23 Based on a literature review, Cheniaux et al⁷ concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.

The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,²⁴ patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.²⁵ Mood symptoms portend a better outcome than do symptoms of schizophrenia.

The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.²⁶ One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).²⁷

Comorbidity

Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.^21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.^27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.³⁰

Clinical assessment

Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.³¹ This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.

Continue to: Differential diagnosis

The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders⁵:

• schizophrenia
• bipolar disorder with psychotic features
• major depressive disorder with psychotic features
• depressive or bipolar disorders with catatonic features
• personality disorders (especially the schizotypal, paranoid, and borderline types)
• major neurocognitive disorders in which there are mood and psychotic symptoms
• substance/medication-induced psychotic disorder
• disorders induced by medical conditions.

With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.

Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.

Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.

Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.

Continue to: Clinical symptoms

The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.

Brain imaging

Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.^32-35 Amann et al³² found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.

Treatment of SAD

The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg, lithium, valproate) or an antidepressant, depending on the patient’s SAD subtype. Jäger et al³⁶ reviewed 33 treatment studies published up to 2007 that employed widely accepted diagnostic criteria and reported results for SAD patients. They concluded that mood stabilizers and antipsychotics appeared to be effective, but that it was not possible to provide treatment guidelines.

Since that exhaustive review, aripiprazole was compared with placebo in 2 separate trials that include patients with schizophrenia and patients with SAD.³⁷ In a pooled sub-analysis of SAD, aripiprazole was found to be more effective on some but not all measures, suggesting efficacy. Based on 2 randomized controlled trials, the FDA approved the use of paliperidone, an SGA, as monotherapy in the acute treatment of SAD and in combination with mood stabilizers and/or antidepressants.^38,39 It is likely that other SGAs are also effective.

Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.⁴⁰ The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.^41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.⁴³ One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.

Continue to: There is a single clinical trial...

There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to lurasidone, although this study had no long-term follow-up.⁴⁴

Other approaches

Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).⁴⁵

As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.

Bottom Line

Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.

Related Resources

• Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
• Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.

Drug Brand Names

Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon

Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.

Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with olanzapine, 20 mg by mouth nightly, with moderate improvement in his symptoms, although he never fully returned to baseline.

Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.

In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.

Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.¹

SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.¹ In this review, we describe the classification of SAD and its features, diagnosis, and treatment.

An evolving diagnosis

The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.² He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.³ In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”³ Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.⁴ These criteria continued to evolve with subsequent editions of the DSM.

Continue to: DSM-5 provides...

DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table⁵). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.⁶ Despite improvements in classification, the diagnosis remains controversial (Box^7-11).

Box 1

DSM-5 subtypes and specifiers

In DSM-5,SAD has 2 subtypes⁵:

• Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
• Depressive type. The depressive type is marked by the presence of only major depressive episodes.

SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.

Epidemiology and gender ratio

The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.⁵ This is similar to an estimate by Perälä et al¹² of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al¹³ calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al¹⁴ estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al¹⁵ based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.

The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.^13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.⁵ The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.²⁰

Continue to: Course and outcome

The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.^21-23 Based on a literature review, Cheniaux et al⁷ concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.

The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,²⁴ patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.²⁵ Mood symptoms portend a better outcome than do symptoms of schizophrenia.

The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.²⁶ One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).²⁷

Comorbidity

Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.^21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.^27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.³⁰

Clinical assessment

Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.³¹ This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.

Continue to: Differential diagnosis

The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders⁵:

• schizophrenia
• bipolar disorder with psychotic features
• major depressive disorder with psychotic features
• depressive or bipolar disorders with catatonic features
• personality disorders (especially the schizotypal, paranoid, and borderline types)
• major neurocognitive disorders in which there are mood and psychotic symptoms
• substance/medication-induced psychotic disorder
• disorders induced by medical conditions.

With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.

Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.

Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.

Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.

Continue to: Clinical symptoms

The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.

Brain imaging

Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.^32-35 Amann et al³² found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.

Treatment of SAD

The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg, lithium, valproate) or an antidepressant, depending on the patient’s SAD subtype. Jäger et al³⁶ reviewed 33 treatment studies published up to 2007 that employed widely accepted diagnostic criteria and reported results for SAD patients. They concluded that mood stabilizers and antipsychotics appeared to be effective, but that it was not possible to provide treatment guidelines.

Since that exhaustive review, aripiprazole was compared with placebo in 2 separate trials that include patients with schizophrenia and patients with SAD.³⁷ In a pooled sub-analysis of SAD, aripiprazole was found to be more effective on some but not all measures, suggesting efficacy. Based on 2 randomized controlled trials, the FDA approved the use of paliperidone, an SGA, as monotherapy in the acute treatment of SAD and in combination with mood stabilizers and/or antidepressants.^38,39 It is likely that other SGAs are also effective.

Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.⁴⁰ The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.^41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.⁴³ One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.

Continue to: There is a single clinical trial...

There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to lurasidone, although this study had no long-term follow-up.⁴⁴

Other approaches

Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).⁴⁵

As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.

Bottom Line

Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.

Related Resources

• Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
• Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.

Drug Brand Names

Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon

Editor’s note:  Career Choices features a psychiatry resident/fellow interviewing a psychiatrist about why he or she has chosen a specific career path. The goal is to inform trainees about the various psychiatric career options, and to give them a feel for the pros and cons of the various paths.

In this Career Choices, Saeed Ahmed, MD, Chief Resident at Nassau University Medical Center, East Meadow, New York, talked with Donald W. Black, MD, Professor of Psychiatry, Department of Psychiatry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa. Dr. Black is also Editor-in-Chief of Annals of Clinical Psychiatry, and Secretary/Treasurer and former President of the American Academy of Clinical Psychiatrists. He is a clinical and translational researcher with more than 300 publications. His work has focused on the course and treatment of severe personality disorders, including researching the effectiveness of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) program for borderline personality disorder. He also conducts family and follow-up studies of behavioral addictions, including gambling disorder.

Dr. Ahmed: What made you choose the academic track, and how did your training lead you towards this path?

Dr. Black: I had always been interested in the idea of working at a medical school, and enjoyed writing and speaking. I was exposed to clinical research as a resident, and that confirmed my interest in academia, because I could envision combining all my interests, along with patient care. I always thought that patients were a major source of ideas for research and writing.

Dr. Ahmed: What are some of the pros and cons of working in academia?

Dr. Black: The pros include being able to influence future physicians through my teaching and writing; being able to pursue important research; and not being isolated from peers. Other advantages are being largely protected from utilization review; having more free time than peers in the private sector, who have difficulty finding coverage; and having defined benefits and a steady salary. I also share call with many peers.

When it comes to the cons, salaries are lower than in the private sector. The cons also include not being my own boss, and sometimes having to bend to the whims of an institution or supervisor.

Continue to: Dr. Ahmed...

Dr. Ahmed: Are you required to conduct research?

Dr. Black: Yes. This is one of the best aspects of my job: being able to make clinical discoveries that I can disseminate through writing and speaking. Over time, this has become increasingly challenging due to the difficulty of obtaining research funding from foundations or the federal government. This has become highly problematic, particularly for clinical researchers, because the National Institutes of Health has clearly been favoring neuroscience.

Dr. Ahmed: What is your typical day like?

Dr. Black: Because of the many hats I wear (or have worn), each day is different from the other. I combine patient care with research, writing, speaking, teaching, and administration. As a tenure-track faculty member, I am expected to write grants, conduct research, and publish. My clinical-track peers primarily provide patient care and teach students and residents.

Dr. Ahmed: What is unique about working in a training institute vs private practice?

Continue to: Dr. Black...

Dr. Black: As an academic psychiatrist, I feel I have the best of both worlds: patient care combined with opportunities my private practice colleagues do not have. Because I have published widely, and have developed a reputation, I am frequently invited to speak at meetings throughout the United States, and sometimes internationally. Travel is a perk of academia, and as someone who loves travel, that is important.

Dr. Ahmed: Where do you see psychiatry going?

Dr. Black: Psychiatry will always be an important specialty because no one else truly cares about patients with psychiatric illnesses. Mental illness will not go away, and society needs highly trained individuals to provide care. There are many “me too” clinicians who now share in caring for patients with psychiatric illnesses, but psychiatrists will always have the most training, and are in a position to provide supervision to others and to direct mental health care teams.

Dr. Ahmed: What advice do you have for residents contemplating a career in academic psychiatry?

Dr. Black: Because most medical schools now have both tenure and clinical tracks, no one needs to feel left out. Those who are interested in scholarly activities will gravitate to the tenure tract, and all that requires in terms of grants and papers, while those who are primarily interested in patient care and teaching will choose the clinical track.

Editor’s note:  Career Choices features a psychiatry resident/fellow interviewing a psychiatrist about why he or she has chosen a specific career path. The goal is to inform trainees about the various psychiatric career options, and to give them a feel for the pros and cons of the various paths.

In this Career Choices, Saeed Ahmed, MD, Chief Resident at Nassau University Medical Center, East Meadow, New York, talked with Donald W. Black, MD, Professor of Psychiatry, Department of Psychiatry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa. Dr. Black is also Editor-in-Chief of Annals of Clinical Psychiatry, and Secretary/Treasurer and former President of the American Academy of Clinical Psychiatrists. He is a clinical and translational researcher with more than 300 publications. His work has focused on the course and treatment of severe personality disorders, including researching the effectiveness of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) program for borderline personality disorder. He also conducts family and follow-up studies of behavioral addictions, including gambling disorder.

Dr. Ahmed: What made you choose the academic track, and how did your training lead you towards this path?

Dr. Black: I had always been interested in the idea of working at a medical school, and enjoyed writing and speaking. I was exposed to clinical research as a resident, and that confirmed my interest in academia, because I could envision combining all my interests, along with patient care. I always thought that patients were a major source of ideas for research and writing.

Dr. Ahmed: What are some of the pros and cons of working in academia?

Dr. Black: The pros include being able to influence future physicians through my teaching and writing; being able to pursue important research; and not being isolated from peers. Other advantages are being largely protected from utilization review; having more free time than peers in the private sector, who have difficulty finding coverage; and having defined benefits and a steady salary. I also share call with many peers.

When it comes to the cons, salaries are lower than in the private sector. The cons also include not being my own boss, and sometimes having to bend to the whims of an institution or supervisor.

Continue to: Dr. Ahmed...

Dr. Ahmed: Are you required to conduct research?

Dr. Black: Yes. This is one of the best aspects of my job: being able to make clinical discoveries that I can disseminate through writing and speaking. Over time, this has become increasingly challenging due to the difficulty of obtaining research funding from foundations or the federal government. This has become highly problematic, particularly for clinical researchers, because the National Institutes of Health has clearly been favoring neuroscience.

Dr. Ahmed: What is your typical day like?

Dr. Black: Because of the many hats I wear (or have worn), each day is different from the other. I combine patient care with research, writing, speaking, teaching, and administration. As a tenure-track faculty member, I am expected to write grants, conduct research, and publish. My clinical-track peers primarily provide patient care and teach students and residents.

Dr. Ahmed: What is unique about working in a training institute vs private practice?

Continue to: Dr. Black...

Dr. Black: As an academic psychiatrist, I feel I have the best of both worlds: patient care combined with opportunities my private practice colleagues do not have. Because I have published widely, and have developed a reputation, I am frequently invited to speak at meetings throughout the United States, and sometimes internationally. Travel is a perk of academia, and as someone who loves travel, that is important.

Dr. Ahmed: Where do you see psychiatry going?

Dr. Black: Psychiatry will always be an important specialty because no one else truly cares about patients with psychiatric illnesses. Mental illness will not go away, and society needs highly trained individuals to provide care. There are many “me too” clinicians who now share in caring for patients with psychiatric illnesses, but psychiatrists will always have the most training, and are in a position to provide supervision to others and to direct mental health care teams.

Dr. Ahmed: What advice do you have for residents contemplating a career in academic psychiatry?

Dr. Black: Because most medical schools now have both tenure and clinical tracks, no one needs to feel left out. Those who are interested in scholarly activities will gravitate to the tenure tract, and all that requires in terms of grants and papers, while those who are primarily interested in patient care and teaching will choose the clinical track.

Editor’s note:  Career Choices features a psychiatry resident/fellow interviewing a psychiatrist about why he or she has chosen a specific career path. The goal is to inform trainees about the various psychiatric career options, and to give them a feel for the pros and cons of the various paths.

In this Career Choices, Saeed Ahmed, MD, Chief Resident at Nassau University Medical Center, East Meadow, New York, talked with Donald W. Black, MD, Professor of Psychiatry, Department of Psychiatry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa. Dr. Black is also Editor-in-Chief of Annals of Clinical Psychiatry, and Secretary/Treasurer and former President of the American Academy of Clinical Psychiatrists. He is a clinical and translational researcher with more than 300 publications. His work has focused on the course and treatment of severe personality disorders, including researching the effectiveness of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) program for borderline personality disorder. He also conducts family and follow-up studies of behavioral addictions, including gambling disorder.

Dr. Ahmed: What made you choose the academic track, and how did your training lead you towards this path?

Dr. Black: I had always been interested in the idea of working at a medical school, and enjoyed writing and speaking. I was exposed to clinical research as a resident, and that confirmed my interest in academia, because I could envision combining all my interests, along with patient care. I always thought that patients were a major source of ideas for research and writing.

Dr. Ahmed: What are some of the pros and cons of working in academia?

Dr. Black: The pros include being able to influence future physicians through my teaching and writing; being able to pursue important research; and not being isolated from peers. Other advantages are being largely protected from utilization review; having more free time than peers in the private sector, who have difficulty finding coverage; and having defined benefits and a steady salary. I also share call with many peers.

When it comes to the cons, salaries are lower than in the private sector. The cons also include not being my own boss, and sometimes having to bend to the whims of an institution or supervisor.

Continue to: Dr. Ahmed...

Dr. Ahmed: Are you required to conduct research?

Dr. Black: Yes. This is one of the best aspects of my job: being able to make clinical discoveries that I can disseminate through writing and speaking. Over time, this has become increasingly challenging due to the difficulty of obtaining research funding from foundations or the federal government. This has become highly problematic, particularly for clinical researchers, because the National Institutes of Health has clearly been favoring neuroscience.

Dr. Ahmed: What is your typical day like?

Dr. Black: Because of the many hats I wear (or have worn), each day is different from the other. I combine patient care with research, writing, speaking, teaching, and administration. As a tenure-track faculty member, I am expected to write grants, conduct research, and publish. My clinical-track peers primarily provide patient care and teach students and residents.

Dr. Ahmed: What is unique about working in a training institute vs private practice?

Continue to: Dr. Black...

Dr. Black: As an academic psychiatrist, I feel I have the best of both worlds: patient care combined with opportunities my private practice colleagues do not have. Because I have published widely, and have developed a reputation, I am frequently invited to speak at meetings throughout the United States, and sometimes internationally. Travel is a perk of academia, and as someone who loves travel, that is important.

Dr. Ahmed: Where do you see psychiatry going?

Dr. Black: Psychiatry will always be an important specialty because no one else truly cares about patients with psychiatric illnesses. Mental illness will not go away, and society needs highly trained individuals to provide care. There are many “me too” clinicians who now share in caring for patients with psychiatric illnesses, but psychiatrists will always have the most training, and are in a position to provide supervision to others and to direct mental health care teams.

Dr. Ahmed: What advice do you have for residents contemplating a career in academic psychiatry?

Dr. Black: Because most medical schools now have both tenure and clinical tracks, no one needs to feel left out. Those who are interested in scholarly activities will gravitate to the tenure tract, and all that requires in terms of grants and papers, while those who are primarily interested in patient care and teaching will choose the clinical track.

A major update to the diagnostic manual used by mental health clinicians around the world is expected to inspire lively debate. Proposed revisions to the personality disorders (PD) section of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is scheduled to be published in 2013, have generated great controversy because they would introduce a dimensional model to the categorical system and 4 PDs would be eliminated.

“The importance of personality functioning and personality traits is the major innovation here,” said Andrew Skodol, MD, the DSM-5 Personality and Personality Disorders Work Group’s chair and a Research Professor of Psychiatry at the University of Arizona College of Medicine. “In the past, we viewed personality disorders as binary. You either had one or you didn’t. But we now understand that personality pathology is a matter of degree.”¹

Mark Zimmerman, MD, has written several papers—some of which are in press—about how these revisions might impact clinicians and whether the revisions are necessary. He is Director of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, an ongoing clinical research study involving the integration of research assessment methods into clinical practice.

Proposed revisions, rationale, and literature reviews for DSM-5 are available at www.DSM5.org and anyone, including the general public, was invited to provide feedback through the Web site. Current Psychiatry Associate Editor Donald W. Black, MD, interviewed Dr. Zimmerman on June 29, 2011, just a few days after the latest proposed revision was posted on June 21, 2011.

DR. BLACK: What is your understanding of the DSM-5 Personality Disorders Work Group proposal to revamp the PD category?

DR. ZIMMERMAN: The initial proposal, released in February 2010, was complex and generated a fair amount of critical commentary related to the marked changes in the approach toward diagnosis of PDs. That proposal replaced diagnostic criteria with a prototype description of personality types that patients would need to match. It also eliminated 5 PDs—paranoid, schizoid, histrionic, dependent, and narcissistic—retained antisocial, avoidant, borderline, obsessive-compulsive, and schizotypal, and introduced trait level ratings. The June 21 revision proposes eliminating only 4 disorders—narcissistic was retained—and the Work Group is no longer suggesting using prototypes but instead have diagnostic criteria (Table).^2,3 We do not know if this is the final proposal because similar to the first proposal, it is not presented with much supporting empirical evidence that demonstrates its superiority toward diagnosing PDs compared with the DSM-IV approach.

Table

Personality disorder criteria: DSM-IV vs DSM-5

I’m not suggesting that the DSM-IV approach is without problems. My attitude is that before going forward with a change to the official diagnostic nomenclature, you need to clearly establish that the new way of doing things is better than the previous way by whatever metric you use.

DR. BLACK: Do you believe there is a need to revamp or revise the DSM-IV PD criteria?

DR. ZIMMERMAN: I think a number of the arguments put forth by the DSM-5 Work Group as justifications for revising the criteria do not hold up to empirical study.

One of the issues is the argument that there’s too much comorbidity among PDs. The theory is that disorders are not unique diagnostic entities if they are so frequently comorbid with other disorders. But how much comorbidity is too much? The DSM-5 Work Group doesn’t say. Oldham et al⁴ found comorbidity rates of 70% to 90%, depending on which semi-structured diagnostic interview was used; however, this was among individuals presenting for psychodynamic treatment of PDs.

I wanted to look at the comorbidity rates in nontreatment-seeking samples to find out if treatment seeking is associated with comorbidity. I reviewed the literature and identified 7 general population epidemiological studies that presented data on the number of individuals with ≥2 PD diagnoses. In these studies, the comorbidity rate is approximately 25%, which is one-half or less than the rates found in patient populations.⁵ This finding suggested to me that this may not be a nosology problem unless you think 25% comorbidity is too high. The DSM-5 people don’t speak to that, although quite frankly with 10 PDs I don’t think the 25% comorbidity rate is excessive. However, a comorbidity rate of 25% was much lower than that found in patient samples and suggests to me that one of the primary stated reasons of deleting 4 PDs may not be valid.

DR. BLACK: Assuming there is a need to revise the PD section, how would you have gone about that process?

DR. ZIMMERMAN: Whatever deficiencies you perceive in the criteria, the process should be that you come up with an alternative, examine the alternative empirically, and this is followed by independent replication that the new approach is superior to the prior one. My view is that it is not sufficient justification to make a change because there is a problem with the prior approach.

We can argue as to whether there really are problems with, for example, the categorical nature of classification. My research group and I wrote a paper arguing that DSM-IV can be interpreted as having a dimensional component (Box).⁶ DSM-IV suggests that clinicians record on axis II that a patient has some traits of a disorder even when the full criteria are not met. With that in mind, we conceptualized DSM-IV as having a 3-point dimension, where 0 means no traits of the disorder, 1 indicates subthreshold traits, and 2 indicates that the disorder is present. In a study of >2,000 patients, we found that DSM-IV’s 3-point dimensional approach was as highly associated with measures of psychosocial morbidity as more finely graded dimensional systems.⁶ We therefore concluded that DSM-IV already includes a dimensional system and questioned why we need to change that approach.

Box

One of my concerns with the dimensional system as currently proposed is the uncertain significance and possible implications of someone being given a low, non-zero rating. How might this play out in a custody evaluation of someone who is said to be “a little borderline”? What might the implications of non-zero ratings be in obtaining life insurance? The potential practical consequences of low ratings have not, to my knowledge, been discussed. Because of this concern we decided to do a study to determine if there was any clinical significance to low dimensional scores. I had hypothesized that if we compared individuals who had no criteria and only 1 BPD criterion, there would be no difference.

To be frank, I was seeking to show that there was no validity to low levels of pathology and therefore the DSM-5 group probably is getting into dangerous territory. In fact, we found that there were rather significant and robust differences between individuals with 0 criteria and 1 criterion.⁷ Even though this finding didn’t support my hypothesis, I thought it was significant because it supported the DSM-5 Work Group and I felt compelled to publish that data.

We now had 2 interesting pieces of information. A few years ago we published a study on borderline personality disorder (BPD) that found once you hit the diagnostic threshold it made no difference how many criteria you met.⁸ On the other hand, when you were below the diagnostic threshold, having 1 criterion vs 0 made a big difference. In addition, a fair number of studies show that dimensional models capture more of the variance in personality pathology than categorical variables.^9-12

This lead to our next study in which we hypothesized that dimensionality was only important when the person didn’t meet criteria, not when they did meet criteria.¹³ So we divided patients in the MIDAS study into those with 0 to 4 BPD criteria and those with ≥5 and counted the number of criteria that were met. Then we correlated each of those 2 dimensional scores with various indicators of illness severity, such as number of suicide attempts, number of psychiatric hospitalizations, and amount of time missed from work in the past 5 years. We found that for individuals who already achieved the diagnostic threshold there were very low correlations with these psychosocial morbidity variables. But for patients with subthreshold symptomatology, there were significant correlations and those correlations were significantly higher than the correlations for the other group. We therefore suggested that dimensionality is important but only when you don’t meet the diagnostic threshold. Thus, we came to the conclusion that DSM-IV already provides for capturing the important dimensional nature of PDs.

DR. BLACK: I’ve discussed this issue with a number of people who basically say doctors tend to think categorically, they don’t think along dimensions. Would it be difficult for psychiatrists to accept this type of system because it’s so different from how physicians are trained to think?

DR. ZIMMERMAN: I think doctors do think categorically and about traits, not necessarily disorders. For example, we’ll see a patient and a clinician will say he’s overly perfectionistic, but there’s no perfectionistic disorder in DSM-IV. This patient may or may not have obsessive-compulsive personality disorder.

I think assessment and diagnosis in routine clinical practice are not nearly as comprehensive as in research. I think psychiatrists often are picking up on traits that they think are clinically significant, but even within that context, they’re thinking categorically, that the patient is perfectionistic rather than rating him a 7 on a scale from 0 to 10 in terms of perfectionism.

Eliminated disorders

DR. BLACK: The proposal will cut the number of PDs to 6 plus personality disorder trait specified and those remaining are to be called types. How did the DSM-5 Work Group select the 5 (now 4) disorders to get rid of? Did they just pick ones that were infrequently used?

DR. ZIMMERMAN: They retained the disorders that were studied in the Collaborative Longitudinal Personality Disorders Study study¹⁴ plus others with well established validity.

DR. BLACK: What do you think about that plan to reduce the number of PDs?

DR. ZIMMERMAN: The biggest problem I have is that the DSM-5 Work Group didn’t present any data on the implications of their plan. The conceptual justification was to reduce comorbidity rates. Well, you can hypothesize that comorbidity would actually increase if you retained only those disorders that are more frequently comorbid with other disorders. Would there be any individuals who only have 1 of the excluded diagnoses? Would there be false negatives? They didn’t indicate whether comorbidity would drop and by how much. And they didn’t indicate if there would be a potential impact on missing cases.

We did such an analysis because we had the data set available from the MIDAS project.¹⁵ We wanted to know if you excluded the 5 diagnoses that (at the time) were proposed for exclusion—narcissistic, paranoid, schizoid, dependent, and histrionic—what percentage of individuals would no longer be diagnosed with a PD? Second, how much would comorbidity rates change? And third, how did individuals who would no longer be diagnosed with a PD compare with individuals who never had a PD?

We found that the comorbidity rates did, in fact, drop from 30% to 21%. We found that the rate of PDs dropped only a little, but approximately 10% of individuals who previously would have been diagnosed with a PD would no longer be diagnosed. We compared individuals in the excluded group—those who had only 1 of the PDs that would no longer be considered a PD—with a group of patients who had a retained PD and also compared them to individuals with no PD. We found that the retained PD group and the excluded group did not differ on measures of psychosocial morbidity, such as Global Assessment of Functioning scores, hospitalizations, suicidality, number of current axis I disorders, etc. Also, the excluded group clearly was different than the no PD group. We questioned whether or not those in the excluded group might end up being false negative diagnoses in DSM-5. Certainly DSM-5 provides a provision to use trait ratings to still diagnose a PD, called personality disorder trait specified, which would be somewhat analogous to PD not otherwise specified (NOS).

It’s ironic insofar as another of the issues considered by the DSM-5 Work Group to be a problem with axis II is lack of coverage and that too many individuals are diagnosed with PD NOS. Their proposal to exclude PDs could result in more individuals being diagnosed with PD NOS. I know the group would disagree with that perspective, but they provided no evidence to support its view.

As I said at the beginning of this interview, I think we should be talking about this from a scientific perspective and nothing more than that.

Related Resource

• Widiger TA, Simonsen E, Sirovatka PJ, et al. Dimensional models of personality disorders: Refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing, Inc; 2007.

Disclosures

• Dr. Zimmerman reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
• Dr. Black receives research support from AstraZeneca and Psyadon.

A major update to the diagnostic manual used by mental health clinicians around the world is expected to inspire lively debate. Proposed revisions to the personality disorders (PD) section of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is scheduled to be published in 2013, have generated great controversy because they would introduce a dimensional model to the categorical system and 4 PDs would be eliminated.

“The importance of personality functioning and personality traits is the major innovation here,” said Andrew Skodol, MD, the DSM-5 Personality and Personality Disorders Work Group’s chair and a Research Professor of Psychiatry at the University of Arizona College of Medicine. “In the past, we viewed personality disorders as binary. You either had one or you didn’t. But we now understand that personality pathology is a matter of degree.”¹

Mark Zimmerman, MD, has written several papers—some of which are in press—about how these revisions might impact clinicians and whether the revisions are necessary. He is Director of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, an ongoing clinical research study involving the integration of research assessment methods into clinical practice.

Proposed revisions, rationale, and literature reviews for DSM-5 are available at www.DSM5.org and anyone, including the general public, was invited to provide feedback through the Web site. Current Psychiatry Associate Editor Donald W. Black, MD, interviewed Dr. Zimmerman on June 29, 2011, just a few days after the latest proposed revision was posted on June 21, 2011.

DR. BLACK: What is your understanding of the DSM-5 Personality Disorders Work Group proposal to revamp the PD category?

DR. ZIMMERMAN: The initial proposal, released in February 2010, was complex and generated a fair amount of critical commentary related to the marked changes in the approach toward diagnosis of PDs. That proposal replaced diagnostic criteria with a prototype description of personality types that patients would need to match. It also eliminated 5 PDs—paranoid, schizoid, histrionic, dependent, and narcissistic—retained antisocial, avoidant, borderline, obsessive-compulsive, and schizotypal, and introduced trait level ratings. The June 21 revision proposes eliminating only 4 disorders—narcissistic was retained—and the Work Group is no longer suggesting using prototypes but instead have diagnostic criteria (Table).^2,3 We do not know if this is the final proposal because similar to the first proposal, it is not presented with much supporting empirical evidence that demonstrates its superiority toward diagnosing PDs compared with the DSM-IV approach.

Table

Personality disorder criteria: DSM-IV vs DSM-5

I’m not suggesting that the DSM-IV approach is without problems. My attitude is that before going forward with a change to the official diagnostic nomenclature, you need to clearly establish that the new way of doing things is better than the previous way by whatever metric you use.

DR. BLACK: Do you believe there is a need to revamp or revise the DSM-IV PD criteria?

DR. ZIMMERMAN: I think a number of the arguments put forth by the DSM-5 Work Group as justifications for revising the criteria do not hold up to empirical study.

One of the issues is the argument that there’s too much comorbidity among PDs. The theory is that disorders are not unique diagnostic entities if they are so frequently comorbid with other disorders. But how much comorbidity is too much? The DSM-5 Work Group doesn’t say. Oldham et al⁴ found comorbidity rates of 70% to 90%, depending on which semi-structured diagnostic interview was used; however, this was among individuals presenting for psychodynamic treatment of PDs.

I wanted to look at the comorbidity rates in nontreatment-seeking samples to find out if treatment seeking is associated with comorbidity. I reviewed the literature and identified 7 general population epidemiological studies that presented data on the number of individuals with ≥2 PD diagnoses. In these studies, the comorbidity rate is approximately 25%, which is one-half or less than the rates found in patient populations.⁵ This finding suggested to me that this may not be a nosology problem unless you think 25% comorbidity is too high. The DSM-5 people don’t speak to that, although quite frankly with 10 PDs I don’t think the 25% comorbidity rate is excessive. However, a comorbidity rate of 25% was much lower than that found in patient samples and suggests to me that one of the primary stated reasons of deleting 4 PDs may not be valid.

DR. BLACK: Assuming there is a need to revise the PD section, how would you have gone about that process?

DR. ZIMMERMAN: Whatever deficiencies you perceive in the criteria, the process should be that you come up with an alternative, examine the alternative empirically, and this is followed by independent replication that the new approach is superior to the prior one. My view is that it is not sufficient justification to make a change because there is a problem with the prior approach.

We can argue as to whether there really are problems with, for example, the categorical nature of classification. My research group and I wrote a paper arguing that DSM-IV can be interpreted as having a dimensional component (Box).⁶ DSM-IV suggests that clinicians record on axis II that a patient has some traits of a disorder even when the full criteria are not met. With that in mind, we conceptualized DSM-IV as having a 3-point dimension, where 0 means no traits of the disorder, 1 indicates subthreshold traits, and 2 indicates that the disorder is present. In a study of >2,000 patients, we found that DSM-IV’s 3-point dimensional approach was as highly associated with measures of psychosocial morbidity as more finely graded dimensional systems.⁶ We therefore concluded that DSM-IV already includes a dimensional system and questioned why we need to change that approach.

Box

One of my concerns with the dimensional system as currently proposed is the uncertain significance and possible implications of someone being given a low, non-zero rating. How might this play out in a custody evaluation of someone who is said to be “a little borderline”? What might the implications of non-zero ratings be in obtaining life insurance? The potential practical consequences of low ratings have not, to my knowledge, been discussed. Because of this concern we decided to do a study to determine if there was any clinical significance to low dimensional scores. I had hypothesized that if we compared individuals who had no criteria and only 1 BPD criterion, there would be no difference.

To be frank, I was seeking to show that there was no validity to low levels of pathology and therefore the DSM-5 group probably is getting into dangerous territory. In fact, we found that there were rather significant and robust differences between individuals with 0 criteria and 1 criterion.⁷ Even though this finding didn’t support my hypothesis, I thought it was significant because it supported the DSM-5 Work Group and I felt compelled to publish that data.

We now had 2 interesting pieces of information. A few years ago we published a study on borderline personality disorder (BPD) that found once you hit the diagnostic threshold it made no difference how many criteria you met.⁸ On the other hand, when you were below the diagnostic threshold, having 1 criterion vs 0 made a big difference. In addition, a fair number of studies show that dimensional models capture more of the variance in personality pathology than categorical variables.^9-12

This lead to our next study in which we hypothesized that dimensionality was only important when the person didn’t meet criteria, not when they did meet criteria.¹³ So we divided patients in the MIDAS study into those with 0 to 4 BPD criteria and those with ≥5 and counted the number of criteria that were met. Then we correlated each of those 2 dimensional scores with various indicators of illness severity, such as number of suicide attempts, number of psychiatric hospitalizations, and amount of time missed from work in the past 5 years. We found that for individuals who already achieved the diagnostic threshold there were very low correlations with these psychosocial morbidity variables. But for patients with subthreshold symptomatology, there were significant correlations and those correlations were significantly higher than the correlations for the other group. We therefore suggested that dimensionality is important but only when you don’t meet the diagnostic threshold. Thus, we came to the conclusion that DSM-IV already provides for capturing the important dimensional nature of PDs.

DR. BLACK: I’ve discussed this issue with a number of people who basically say doctors tend to think categorically, they don’t think along dimensions. Would it be difficult for psychiatrists to accept this type of system because it’s so different from how physicians are trained to think?

DR. ZIMMERMAN: I think doctors do think categorically and about traits, not necessarily disorders. For example, we’ll see a patient and a clinician will say he’s overly perfectionistic, but there’s no perfectionistic disorder in DSM-IV. This patient may or may not have obsessive-compulsive personality disorder.

I think assessment and diagnosis in routine clinical practice are not nearly as comprehensive as in research. I think psychiatrists often are picking up on traits that they think are clinically significant, but even within that context, they’re thinking categorically, that the patient is perfectionistic rather than rating him a 7 on a scale from 0 to 10 in terms of perfectionism.

Eliminated disorders

DR. BLACK: The proposal will cut the number of PDs to 6 plus personality disorder trait specified and those remaining are to be called types. How did the DSM-5 Work Group select the 5 (now 4) disorders to get rid of? Did they just pick ones that were infrequently used?

DR. ZIMMERMAN: They retained the disorders that were studied in the Collaborative Longitudinal Personality Disorders Study study¹⁴ plus others with well established validity.

DR. BLACK: What do you think about that plan to reduce the number of PDs?

DR. ZIMMERMAN: The biggest problem I have is that the DSM-5 Work Group didn’t present any data on the implications of their plan. The conceptual justification was to reduce comorbidity rates. Well, you can hypothesize that comorbidity would actually increase if you retained only those disorders that are more frequently comorbid with other disorders. Would there be any individuals who only have 1 of the excluded diagnoses? Would there be false negatives? They didn’t indicate whether comorbidity would drop and by how much. And they didn’t indicate if there would be a potential impact on missing cases.

We did such an analysis because we had the data set available from the MIDAS project.¹⁵ We wanted to know if you excluded the 5 diagnoses that (at the time) were proposed for exclusion—narcissistic, paranoid, schizoid, dependent, and histrionic—what percentage of individuals would no longer be diagnosed with a PD? Second, how much would comorbidity rates change? And third, how did individuals who would no longer be diagnosed with a PD compare with individuals who never had a PD?

We found that the comorbidity rates did, in fact, drop from 30% to 21%. We found that the rate of PDs dropped only a little, but approximately 10% of individuals who previously would have been diagnosed with a PD would no longer be diagnosed. We compared individuals in the excluded group—those who had only 1 of the PDs that would no longer be considered a PD—with a group of patients who had a retained PD and also compared them to individuals with no PD. We found that the retained PD group and the excluded group did not differ on measures of psychosocial morbidity, such as Global Assessment of Functioning scores, hospitalizations, suicidality, number of current axis I disorders, etc. Also, the excluded group clearly was different than the no PD group. We questioned whether or not those in the excluded group might end up being false negative diagnoses in DSM-5. Certainly DSM-5 provides a provision to use trait ratings to still diagnose a PD, called personality disorder trait specified, which would be somewhat analogous to PD not otherwise specified (NOS).

It’s ironic insofar as another of the issues considered by the DSM-5 Work Group to be a problem with axis II is lack of coverage and that too many individuals are diagnosed with PD NOS. Their proposal to exclude PDs could result in more individuals being diagnosed with PD NOS. I know the group would disagree with that perspective, but they provided no evidence to support its view.

As I said at the beginning of this interview, I think we should be talking about this from a scientific perspective and nothing more than that.

Related Resource

• Widiger TA, Simonsen E, Sirovatka PJ, et al. Dimensional models of personality disorders: Refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing, Inc; 2007.

Disclosures

• Dr. Zimmerman reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
• Dr. Black receives research support from AstraZeneca and Psyadon.

A major update to the diagnostic manual used by mental health clinicians around the world is expected to inspire lively debate. Proposed revisions to the personality disorders (PD) section of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is scheduled to be published in 2013, have generated great controversy because they would introduce a dimensional model to the categorical system and 4 PDs would be eliminated.

“The importance of personality functioning and personality traits is the major innovation here,” said Andrew Skodol, MD, the DSM-5 Personality and Personality Disorders Work Group’s chair and a Research Professor of Psychiatry at the University of Arizona College of Medicine. “In the past, we viewed personality disorders as binary. You either had one or you didn’t. But we now understand that personality pathology is a matter of degree.”¹

Mark Zimmerman, MD, has written several papers—some of which are in press—about how these revisions might impact clinicians and whether the revisions are necessary. He is Director of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, an ongoing clinical research study involving the integration of research assessment methods into clinical practice.

Proposed revisions, rationale, and literature reviews for DSM-5 are available at www.DSM5.org and anyone, including the general public, was invited to provide feedback through the Web site. Current Psychiatry Associate Editor Donald W. Black, MD, interviewed Dr. Zimmerman on June 29, 2011, just a few days after the latest proposed revision was posted on June 21, 2011.

DR. BLACK: What is your understanding of the DSM-5 Personality Disorders Work Group proposal to revamp the PD category?

DR. ZIMMERMAN: The initial proposal, released in February 2010, was complex and generated a fair amount of critical commentary related to the marked changes in the approach toward diagnosis of PDs. That proposal replaced diagnostic criteria with a prototype description of personality types that patients would need to match. It also eliminated 5 PDs—paranoid, schizoid, histrionic, dependent, and narcissistic—retained antisocial, avoidant, borderline, obsessive-compulsive, and schizotypal, and introduced trait level ratings. The June 21 revision proposes eliminating only 4 disorders—narcissistic was retained—and the Work Group is no longer suggesting using prototypes but instead have diagnostic criteria (Table).^2,3 We do not know if this is the final proposal because similar to the first proposal, it is not presented with much supporting empirical evidence that demonstrates its superiority toward diagnosing PDs compared with the DSM-IV approach.

Table

Personality disorder criteria: DSM-IV vs DSM-5

I’m not suggesting that the DSM-IV approach is without problems. My attitude is that before going forward with a change to the official diagnostic nomenclature, you need to clearly establish that the new way of doing things is better than the previous way by whatever metric you use.

DR. BLACK: Do you believe there is a need to revamp or revise the DSM-IV PD criteria?

DR. ZIMMERMAN: I think a number of the arguments put forth by the DSM-5 Work Group as justifications for revising the criteria do not hold up to empirical study.

One of the issues is the argument that there’s too much comorbidity among PDs. The theory is that disorders are not unique diagnostic entities if they are so frequently comorbid with other disorders. But how much comorbidity is too much? The DSM-5 Work Group doesn’t say. Oldham et al⁴ found comorbidity rates of 70% to 90%, depending on which semi-structured diagnostic interview was used; however, this was among individuals presenting for psychodynamic treatment of PDs.

I wanted to look at the comorbidity rates in nontreatment-seeking samples to find out if treatment seeking is associated with comorbidity. I reviewed the literature and identified 7 general population epidemiological studies that presented data on the number of individuals with ≥2 PD diagnoses. In these studies, the comorbidity rate is approximately 25%, which is one-half or less than the rates found in patient populations.⁵ This finding suggested to me that this may not be a nosology problem unless you think 25% comorbidity is too high. The DSM-5 people don’t speak to that, although quite frankly with 10 PDs I don’t think the 25% comorbidity rate is excessive. However, a comorbidity rate of 25% was much lower than that found in patient samples and suggests to me that one of the primary stated reasons of deleting 4 PDs may not be valid.

DR. BLACK: Assuming there is a need to revise the PD section, how would you have gone about that process?

DR. ZIMMERMAN: Whatever deficiencies you perceive in the criteria, the process should be that you come up with an alternative, examine the alternative empirically, and this is followed by independent replication that the new approach is superior to the prior one. My view is that it is not sufficient justification to make a change because there is a problem with the prior approach.

We can argue as to whether there really are problems with, for example, the categorical nature of classification. My research group and I wrote a paper arguing that DSM-IV can be interpreted as having a dimensional component (Box).⁶ DSM-IV suggests that clinicians record on axis II that a patient has some traits of a disorder even when the full criteria are not met. With that in mind, we conceptualized DSM-IV as having a 3-point dimension, where 0 means no traits of the disorder, 1 indicates subthreshold traits, and 2 indicates that the disorder is present. In a study of >2,000 patients, we found that DSM-IV’s 3-point dimensional approach was as highly associated with measures of psychosocial morbidity as more finely graded dimensional systems.⁶ We therefore concluded that DSM-IV already includes a dimensional system and questioned why we need to change that approach.

Box

One of my concerns with the dimensional system as currently proposed is the uncertain significance and possible implications of someone being given a low, non-zero rating. How might this play out in a custody evaluation of someone who is said to be “a little borderline”? What might the implications of non-zero ratings be in obtaining life insurance? The potential practical consequences of low ratings have not, to my knowledge, been discussed. Because of this concern we decided to do a study to determine if there was any clinical significance to low dimensional scores. I had hypothesized that if we compared individuals who had no criteria and only 1 BPD criterion, there would be no difference.

To be frank, I was seeking to show that there was no validity to low levels of pathology and therefore the DSM-5 group probably is getting into dangerous territory. In fact, we found that there were rather significant and robust differences between individuals with 0 criteria and 1 criterion.⁷ Even though this finding didn’t support my hypothesis, I thought it was significant because it supported the DSM-5 Work Group and I felt compelled to publish that data.

We now had 2 interesting pieces of information. A few years ago we published a study on borderline personality disorder (BPD) that found once you hit the diagnostic threshold it made no difference how many criteria you met.⁸ On the other hand, when you were below the diagnostic threshold, having 1 criterion vs 0 made a big difference. In addition, a fair number of studies show that dimensional models capture more of the variance in personality pathology than categorical variables.^9-12

This lead to our next study in which we hypothesized that dimensionality was only important when the person didn’t meet criteria, not when they did meet criteria.¹³ So we divided patients in the MIDAS study into those with 0 to 4 BPD criteria and those with ≥5 and counted the number of criteria that were met. Then we correlated each of those 2 dimensional scores with various indicators of illness severity, such as number of suicide attempts, number of psychiatric hospitalizations, and amount of time missed from work in the past 5 years. We found that for individuals who already achieved the diagnostic threshold there were very low correlations with these psychosocial morbidity variables. But for patients with subthreshold symptomatology, there were significant correlations and those correlations were significantly higher than the correlations for the other group. We therefore suggested that dimensionality is important but only when you don’t meet the diagnostic threshold. Thus, we came to the conclusion that DSM-IV already provides for capturing the important dimensional nature of PDs.

DR. BLACK: I’ve discussed this issue with a number of people who basically say doctors tend to think categorically, they don’t think along dimensions. Would it be difficult for psychiatrists to accept this type of system because it’s so different from how physicians are trained to think?

DR. ZIMMERMAN: I think doctors do think categorically and about traits, not necessarily disorders. For example, we’ll see a patient and a clinician will say he’s overly perfectionistic, but there’s no perfectionistic disorder in DSM-IV. This patient may or may not have obsessive-compulsive personality disorder.

I think assessment and diagnosis in routine clinical practice are not nearly as comprehensive as in research. I think psychiatrists often are picking up on traits that they think are clinically significant, but even within that context, they’re thinking categorically, that the patient is perfectionistic rather than rating him a 7 on a scale from 0 to 10 in terms of perfectionism.

Eliminated disorders

DR. BLACK: The proposal will cut the number of PDs to 6 plus personality disorder trait specified and those remaining are to be called types. How did the DSM-5 Work Group select the 5 (now 4) disorders to get rid of? Did they just pick ones that were infrequently used?

DR. ZIMMERMAN: They retained the disorders that were studied in the Collaborative Longitudinal Personality Disorders Study study¹⁴ plus others with well established validity.

DR. BLACK: What do you think about that plan to reduce the number of PDs?

DR. ZIMMERMAN: The biggest problem I have is that the DSM-5 Work Group didn’t present any data on the implications of their plan. The conceptual justification was to reduce comorbidity rates. Well, you can hypothesize that comorbidity would actually increase if you retained only those disorders that are more frequently comorbid with other disorders. Would there be any individuals who only have 1 of the excluded diagnoses? Would there be false negatives? They didn’t indicate whether comorbidity would drop and by how much. And they didn’t indicate if there would be a potential impact on missing cases.

We did such an analysis because we had the data set available from the MIDAS project.¹⁵ We wanted to know if you excluded the 5 diagnoses that (at the time) were proposed for exclusion—narcissistic, paranoid, schizoid, dependent, and histrionic—what percentage of individuals would no longer be diagnosed with a PD? Second, how much would comorbidity rates change? And third, how did individuals who would no longer be diagnosed with a PD compare with individuals who never had a PD?

We found that the comorbidity rates did, in fact, drop from 30% to 21%. We found that the rate of PDs dropped only a little, but approximately 10% of individuals who previously would have been diagnosed with a PD would no longer be diagnosed. We compared individuals in the excluded group—those who had only 1 of the PDs that would no longer be considered a PD—with a group of patients who had a retained PD and also compared them to individuals with no PD. We found that the retained PD group and the excluded group did not differ on measures of psychosocial morbidity, such as Global Assessment of Functioning scores, hospitalizations, suicidality, number of current axis I disorders, etc. Also, the excluded group clearly was different than the no PD group. We questioned whether or not those in the excluded group might end up being false negative diagnoses in DSM-5. Certainly DSM-5 provides a provision to use trait ratings to still diagnose a PD, called personality disorder trait specified, which would be somewhat analogous to PD not otherwise specified (NOS).

It’s ironic insofar as another of the issues considered by the DSM-5 Work Group to be a problem with axis II is lack of coverage and that too many individuals are diagnosed with PD NOS. Their proposal to exclude PDs could result in more individuals being diagnosed with PD NOS. I know the group would disagree with that perspective, but they provided no evidence to support its view.

As I said at the beginning of this interview, I think we should be talking about this from a scientific perspective and nothing more than that.

Related Resource

• Widiger TA, Simonsen E, Sirovatka PJ, et al. Dimensional models of personality disorders: Refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing, Inc; 2007.

Disclosures

• Dr. Zimmerman reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
• Dr. Black receives research support from AstraZeneca and Psyadon.