Philip R. Muskin, MD

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Mr. G, a 28-year-old heterosexual Puerto Rican man, is admitted to the hospital’s infectious diseases (ID) unit after 3 weeks of worsening bifrontal headaches. He has been treated as an outpatient for several years since becoming HIV-positive and was diagnosed with AIDS after an intracranial toxoplasmosis infection. Although he has not taken antiretrovirals for several months, Mr. G has adhered intermittently to his antiretroviral regimen and previously developed other opportunistic infections, including thrush and bacterial pneumonia.

Three days after Mr. G is admitted, ID clinicians become concerned that he appears severely depressed and request a psychiatric evaluation.

Psychiatric evaluation and diagnosis in patients with HIV can be a challenge because of:

• the myriad ways HIV can impact the CNS
  
• the proliferation of antiretroviral medications
  
• patients’ increasing lifespan as a result of highly active antiretroviral therapy (HAART)¹
  
• the psychological repercussions of living with HIV infection.
  

In this case-based review, we outline a rational, 5-step approach to evaluating and diagnosing psychiatric symptoms in patients with HIV.

A wide differential diagnosis

Patients who are HIV-positive have disproportionately high rates of psychiatric disorders. One study of approximately 2,800 adults receiving care for HIV found that nearly one-half screened positive for major depression, dysthymia, generalized anxiety disorders, or panic attacks.² Some psychiatric morbidity may be related to:

• the stress of having HIV
  
• stressors related to risk factors for acquiring HIV, including low socioeconomic status, homelessness, and discrimination and social stigma based on race and sexual orientation
  
• substance abuse, which is common among patients with HIV.²
  

Other “psychiatric” symptoms may be the result of HIV infection in the brain, either acutely (as seen in HIV encephalopathy³) or cumulatively (as seen in AIDS-associated dementia⁴). Psychiatric symptoms may be the result of intracranial opportunistic infections in immunocompromised AIDS patients (Table 1).^5-8 Antiretroviral medications commonly used to treat HIV also can cause psychiatric symptoms (Table 2).^9,10

Because of the range and variety of psychopathology encountered in HIV disease, keep a wide differential diagnosis in mind when evaluating patients with HIV.

A 5-step process can help you determine if symptoms in any patient—regardless of HIV status—are caused by a primary psychiatric disorder or CNS impairment (Box).

Table 1

HIV-associated CNS infections

More common
Cryptococcus neoformans meningitis
Progressive multifocal leukoencephalopathy (polyomavirus JC)
Toxoplasma gondii
Less common
Aspergillosis
Coccidioidomycosis
Cytomegalovirus
Herpes simplex or varicella-zoster encephalitis
Histoplasmosis
Leptomeningeal tuberculosis
Source: References 5-8

Table 2

Neuropsychiatric side effects of antiretroviral medications

Medication	Potential side effect(s)
Abacavir	Depression, anxiety, psychosis
Amprenavir	Mood changes
Didanosine	Lethargy, nervousness, anxiety, confusion, sleep disturbances, mood disorders, psychosis
Efavirenz	Agitation, depersonalization, hallucinations, disturbed dreams, mood disorders, depression, suicidality, antisocial behavior, psychosis, catatonia, delirium
Enfuvirtide	Anxiety, depression
Indinavir	Mood changes
Lamivudine	Insomnia, mood disorders
Lopinavir+Ritonavir	Mood changes, agitation, anxiety
Nevirapine	Depression, cognitive impairment, psychosis
Ritonavir	Anxiety
Saquinavir	Depression, anxiety, sleep disturbances
Stavudine	Sleep disorders, mood disorders, delirium
Zalcitabine	Somnolence, impaired concentration, mood disorders, delirium
Zidovudine	Sleep disturbance, vivid dreams, agitation, mania, depression, psychotic symptoms, delirium
Source: References 9,10

STEP 1 Perform initial exams

A careful diagnostic exam that includes a mental status examination with gross cognitive functioning testing is necessary to differentiate primary psychiatric disorders from HIV-related CNS pathology, including:

• HIV-associated dementia
  
• HIV-associated minor cognitive motor disorder (a less severe form of HIV-related cognitive and psychomotor impairment)
  
• opportunistic infections.
  

CASE CONTINUED

Mr. G sits in a chair alone in his room, looking out the window. He responds minimally to your initial greetings and has a staring expression and flat affect. Mr. G is calm and cooperative with the exam but has almost no spontaneous speech, answering questions with slow, imprecise 3- or 4-word responses. He is relaxed and does not seem guarded or paranoid.

Mr. G denies depressed mood or suicidal thinking and appears surprised to be asked about these symptoms. He also denies a history of manic or psychotic symptoms or problems with sleep, appetite, or energy. Bedside cognitive exam—focusing on alertness, orientation, attention, and memory—does not demonstrate any gross deficits.

Cognitive workup. Be vigilant for deficits in attention and orientation that might indicate an acute brain syndrome. In addition, look for discrepant patterns of symptoms or other features that may suggest CNS pathology. For example, Mr. G’s impoverished speech and lack of motivation—combined with a clear sensorium and lack of obvious patterns of mood, anxiety, or psychotic symptoms—suggest that a primary psychiatric disorder might not explain his presentation.

Although commonly used, the bedside Mini-Mental State Examination may be insensitive to cognitive deficits in HIV-associated dementia. The HIV-Dementia Scale is more sensitive to HIV’s typical subcortical features.

Physical workup. When evaluating symptoms in an immunocompromised patient at risk for opportunistic infections, it is important to conduct a comprehensive physical exam. Pay attention to evidence of secondary infection and to neurologic signs. Fever may suggest an opportunistic infection that could contribute to psychiatric symptoms. Immunocompromise in HIV may be associated with a variety of infectious meningitis forms, such as:

 

• cryptococcus
  
• aseptic meningitis (which may be caused by HIV)
  
• histoplasmosis
  
• coccidioidomycosis.
  

A stiff neck or positive Kernig’s and Brudzinski’s signs (pain elicited upon passive extension of the knee with the hip flexed, or with flexion of the neck) specifically indicate an infection or other inflammatory process within the meninges that may lead to mental status changes. Motor, sensory, and cranial nerve examinations can detect evidence of intracranial mass lesions resulting from CNS neoplasms or infections to which immunocompromised patients are vulnerable.

CASE CONTINUED

Physical exam reveals that Mr. G has a low-grade fever (100.2° F) and penile erosion consistent with herpes simplex infection. He has no meningeal signs and an otherwise normal neurologic examination.

STEP 2 Evaluate lab results

Use laboratory testing to search for potential medical causes of the patient’s presentation. Include a complete blood cell count, electrolytes, blood urea nitrogen and creatinine, and liver function tests to look for underlying metabolic problems.

CASE CONTINUED

Complete blood count, electrolytes, kidney function, and liver function tests are all within normal limits, and rapid plasma reagin (RPR) for syphilis is negative. Cerebrospinal fluid (CSF) analysis demonstrates normal opening pressures, protein, and glucose. India ink stain is negative for Cryptococcus neoformans, but 1 week later CSF cultures are positive for Cryptococcus. The patient has a CD4 count of 15 and a viral load of approximately 44,000.

In patients with HIV, CD4 count can reveal the degree of immunocompromise, whereas viral load shows the extent of viral activity. Typically, patients with a CD4 count >500 are not at risk for opportunistic infections. A count

Box

Carefully evaluate patients with a CD4 count

Strongly consider ordering the RPR test for syphilis because:

 

• HIV and syphilis share sexual risk factors
  
• having syphilis increases the likelihood of comorbid HIV infection 7- to 9-fold¹¹
  
• syphilis may worsen the course of HIV infection¹²
  
• syphilis can mimic psychiatric symptoms.^13,14
  

CSF analysis may reveal evidence of meningitis, and special stains may be used to detect meningitis-causing organisms that are characteristic of AIDS. CSF also may be tested directly for CNS syphilis.

STEP 3 Order neuroimaging

Neuroimaging is an essential part of the workup of a patient for whom your clinical examination raises suspicion for CNS impairment. In patients with longstanding HIV infection, brain imaging may reveal cerebral atrophy, which may accompany the cognitive changes found in HIV-associated dementia. In addition, immunocompromised patients, particularly those with a CD4 count 15

CASE CONTINUED

Brain MRI shows moderate cerebral and cerebellar atrophy, which ID clinicians attribute to the long-term effects of HIV infection. No evidence of focal or mass lesions is seen.

By further investigating Mr. G’s medical records, you find a brain MRI performed when Mr. G initially presented with toxoplasmosis in 2001. This scan reveals a large ring-enhancing mass in the right frontal lobe. Although the patient had refused a brain biopsy, the radiologist determined the lesion was most consistent in appearance with intracranial toxoplasmosis.

STEP 4 Perform neuropsychological testing

When physical exam, mental status exam, or neuroimaging suggests a possible CNS cause for a patient’s psychiatric presentation, neuropsychological testing can help characterize which of the patient’s brain functions are compromised and determine their anatomic source. This testing allows for a more complete and precise assessment of brain function than can be achieved by a bedside cognitive exam. It typically includes the Trail Making Test Parts A and B and the Grooved Pegboard Test to evaluate executive and psychomotor functioning, as well as the Controlled Oral Word Association Test to evaluate cognitive speed.

CASE CONTINUED

A search of medical records reveals that Mr. G had recently undergone a brief neuropsychological assessment at the hospital’s outpatient HIV mental health clinic. The psychologist found evidence of frontal lobe dysfunction, including problems with shifting sets, verbal fluency, and naming the months of the year backwards. Mr. G’s performance demonstrated a subcortical dementia pattern that included prominent fine motor impairment.

In HIV-positive patients with evidence of cognitive impairment, neuropsychological testing can help determine if the pattern of deficits is consistent with HIV-associated dementia. Such deficits typically follow the pattern of a subcortical dementia characterized by apathy, amotivation, psychomotor retardation, and slowing of general information processing. This differentiates it from Alzheimer’s dementia, which is typically characterized by shortterm memory impairment, personality changes, and affective changes such as depression.

STEP 5 Synthesize all data to make a diagnosis

Psychiatric illness in HIV-positive patients may involve factors at multiple biopsychosocial levels, including problems with social support, psychological stress, primary psychiatric illness, immunocompromise, and CNS disease. Consider data from all of these levels to arrive at a diagnosis.

CASE CONTINUED

After carefully considering Mr. G’s history, physical and mental status examinations, laboratory data, current and past neuroimaging, and neuropsychological testing, you and ID clinicians conclude that Mr. G’s neuropsychiatric presentation primarily represents the residual deficits from his large frontal lobe toxoplasmosis lesion diagnosed in 2001, with possible contribution from an underlying HIV-associated dementia. You feel that a depressive disorder can be ruled out with a high degree of certainty because the patient denied abnormalities of mood or hedonic tone, did not demonstrate deficits in neurovegetative functioning such as appetite, energy, and sleep, and did not show evidence of suicidality. You attribute the flat affect and amotivation that had prompted the psychiatric consult to his secondary neuropsychiatric deficits.

In the absence of another neurologic diagnosis, Mr. G would likely be classified as having Stage 1 HIV-associated dementia. (Table 3).^9,16 However, it is difficult to determine which of his deficits are due to an underlying HIV-related dementing process and which are related to his more focal frontal lobe compromise demonstrated on neuropsychological testing.

Table 3

Staging system for HIV-associated dementia

Stage	Degree of severity	Clinical characteristics
0	Normal	Normal mental and motor function
0.5	Equivocal	Minimal or equivocal symptoms characteristic of cognitive or motor dysfunction, or mild signs (snout response or slowed extremity movements); no impairment of work or ADLs; gait and strength normal
1	Mild	Unequivocal evidence of functional, intellectual, or motor impairment (including symptoms, signs, or neuropsychological testing); can walk without assistance and perform all except more demanding aspects of work or ADLs
2	Moderate	Able to perform basic activities of self care but unable to work or maintain the more demanding ADLs; ambulatory but may require a single prop
3	Severe	Major intellectual incapacity (cannot follow news or personal events, cannot sustain complex conversation, considerable slowing of all outputs) or motor disability (unable to walk unassisted, requires walker or personal support, usually slowed and accompanied by clumsiness of arms)
4	End stage	A nearly vegetative state; intellectual and social comprehension and output are rudimentary; patient is nearly or absolutely mute and paraparetic or paraplegic, with urinary and fecal incontinence
ADLs: activities of daily living
Source: References 9,16

 

CASE CONTINUED

Because Mr. G had no evidence of a mood syndrome, you do not recommend antidepressants. You note that although a stimulant might improve the patient’s cognitive function and apathy, Mr. G’s history of heavy cocaine use is considered a contraindication.

Mr. G’s cognitive and motivation deficits will complicate the management of his complex medical condition and medications. You recommend that he be referred to a structured outpatient living and care environment to support his HAART adherence. Despite the primary team’s efforts in discharge planning, however, the patient does not keep his clinic appointments and is lost to follow-up.

Related Resources

• Aidsmap information on AIDS and HIV. www.aidsmap.com.
  
• America Psychiatric Association AIDS Resource Center. www.psych.org/AIDS.
  

Drug brand names

• Abacavir • Ziagen
  
• Amprenavir • Agenerase
  
• Didanosine • Videx
  
• Efavirenz • Sustiva
  
• Enfuvirtide • Fuzeon
  
• Indinavir • Crixivan
  
• Lamivudine • Epivir
  
• Lopinavir/Ritonavir • Kaletra
  
• Nevirapine • Viramune
  
• Pyrimethamine • Daraprim
  
• Ritonavir • Norvir
  
• Saquinavir • Invirase
  
• Stavudine • Zerit
  
• Sulfadiazine • Microsulfon
  
• Zalcitabine • Hivid
  
• Zidovudine • Retrovir
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Mr. G, a 28-year-old heterosexual Puerto Rican man, is admitted to the hospital’s infectious diseases (ID) unit after 3 weeks of worsening bifrontal headaches. He has been treated as an outpatient for several years since becoming HIV-positive and was diagnosed with AIDS after an intracranial toxoplasmosis infection. Although he has not taken antiretrovirals for several months, Mr. G has adhered intermittently to his antiretroviral regimen and previously developed other opportunistic infections, including thrush and bacterial pneumonia.

Three days after Mr. G is admitted, ID clinicians become concerned that he appears severely depressed and request a psychiatric evaluation.

Psychiatric evaluation and diagnosis in patients with HIV can be a challenge because of:

• the myriad ways HIV can impact the CNS
  
• the proliferation of antiretroviral medications
  
• patients’ increasing lifespan as a result of highly active antiretroviral therapy (HAART)¹
  
• the psychological repercussions of living with HIV infection.
  

In this case-based review, we outline a rational, 5-step approach to evaluating and diagnosing psychiatric symptoms in patients with HIV.

A wide differential diagnosis

Patients who are HIV-positive have disproportionately high rates of psychiatric disorders. One study of approximately 2,800 adults receiving care for HIV found that nearly one-half screened positive for major depression, dysthymia, generalized anxiety disorders, or panic attacks.² Some psychiatric morbidity may be related to:

• the stress of having HIV
  
• stressors related to risk factors for acquiring HIV, including low socioeconomic status, homelessness, and discrimination and social stigma based on race and sexual orientation
  
• substance abuse, which is common among patients with HIV.²
  

Other “psychiatric” symptoms may be the result of HIV infection in the brain, either acutely (as seen in HIV encephalopathy³) or cumulatively (as seen in AIDS-associated dementia⁴). Psychiatric symptoms may be the result of intracranial opportunistic infections in immunocompromised AIDS patients (Table 1).^5-8 Antiretroviral medications commonly used to treat HIV also can cause psychiatric symptoms (Table 2).^9,10

Because of the range and variety of psychopathology encountered in HIV disease, keep a wide differential diagnosis in mind when evaluating patients with HIV.

A 5-step process can help you determine if symptoms in any patient—regardless of HIV status—are caused by a primary psychiatric disorder or CNS impairment (Box).

Table 1

HIV-associated CNS infections

More common
Cryptococcus neoformans meningitis
Progressive multifocal leukoencephalopathy (polyomavirus JC)
Toxoplasma gondii
Less common
Aspergillosis
Coccidioidomycosis
Cytomegalovirus
Herpes simplex or varicella-zoster encephalitis
Histoplasmosis
Leptomeningeal tuberculosis
Source: References 5-8

Table 2

Neuropsychiatric side effects of antiretroviral medications

Medication	Potential side effect(s)
Abacavir	Depression, anxiety, psychosis
Amprenavir	Mood changes
Didanosine	Lethargy, nervousness, anxiety, confusion, sleep disturbances, mood disorders, psychosis
Efavirenz	Agitation, depersonalization, hallucinations, disturbed dreams, mood disorders, depression, suicidality, antisocial behavior, psychosis, catatonia, delirium
Enfuvirtide	Anxiety, depression
Indinavir	Mood changes
Lamivudine	Insomnia, mood disorders
Lopinavir+Ritonavir	Mood changes, agitation, anxiety
Nevirapine	Depression, cognitive impairment, psychosis
Ritonavir	Anxiety
Saquinavir	Depression, anxiety, sleep disturbances
Stavudine	Sleep disorders, mood disorders, delirium
Zalcitabine	Somnolence, impaired concentration, mood disorders, delirium
Zidovudine	Sleep disturbance, vivid dreams, agitation, mania, depression, psychotic symptoms, delirium
Source: References 9,10

STEP 1 Perform initial exams

A careful diagnostic exam that includes a mental status examination with gross cognitive functioning testing is necessary to differentiate primary psychiatric disorders from HIV-related CNS pathology, including:

• HIV-associated dementia
  
• HIV-associated minor cognitive motor disorder (a less severe form of HIV-related cognitive and psychomotor impairment)
  
• opportunistic infections.
  

CASE CONTINUED

Mr. G sits in a chair alone in his room, looking out the window. He responds minimally to your initial greetings and has a staring expression and flat affect. Mr. G is calm and cooperative with the exam but has almost no spontaneous speech, answering questions with slow, imprecise 3- or 4-word responses. He is relaxed and does not seem guarded or paranoid.

Mr. G denies depressed mood or suicidal thinking and appears surprised to be asked about these symptoms. He also denies a history of manic or psychotic symptoms or problems with sleep, appetite, or energy. Bedside cognitive exam—focusing on alertness, orientation, attention, and memory—does not demonstrate any gross deficits.

Cognitive workup. Be vigilant for deficits in attention and orientation that might indicate an acute brain syndrome. In addition, look for discrepant patterns of symptoms or other features that may suggest CNS pathology. For example, Mr. G’s impoverished speech and lack of motivation—combined with a clear sensorium and lack of obvious patterns of mood, anxiety, or psychotic symptoms—suggest that a primary psychiatric disorder might not explain his presentation.

Although commonly used, the bedside Mini-Mental State Examination may be insensitive to cognitive deficits in HIV-associated dementia. The HIV-Dementia Scale is more sensitive to HIV’s typical subcortical features.

Physical workup. When evaluating symptoms in an immunocompromised patient at risk for opportunistic infections, it is important to conduct a comprehensive physical exam. Pay attention to evidence of secondary infection and to neurologic signs. Fever may suggest an opportunistic infection that could contribute to psychiatric symptoms. Immunocompromise in HIV may be associated with a variety of infectious meningitis forms, such as:

 

• cryptococcus
  
• aseptic meningitis (which may be caused by HIV)
  
• histoplasmosis
  
• coccidioidomycosis.
  

A stiff neck or positive Kernig’s and Brudzinski’s signs (pain elicited upon passive extension of the knee with the hip flexed, or with flexion of the neck) specifically indicate an infection or other inflammatory process within the meninges that may lead to mental status changes. Motor, sensory, and cranial nerve examinations can detect evidence of intracranial mass lesions resulting from CNS neoplasms or infections to which immunocompromised patients are vulnerable.

CASE CONTINUED

Physical exam reveals that Mr. G has a low-grade fever (100.2° F) and penile erosion consistent with herpes simplex infection. He has no meningeal signs and an otherwise normal neurologic examination.

STEP 2 Evaluate lab results

Use laboratory testing to search for potential medical causes of the patient’s presentation. Include a complete blood cell count, electrolytes, blood urea nitrogen and creatinine, and liver function tests to look for underlying metabolic problems.

CASE CONTINUED

Complete blood count, electrolytes, kidney function, and liver function tests are all within normal limits, and rapid plasma reagin (RPR) for syphilis is negative. Cerebrospinal fluid (CSF) analysis demonstrates normal opening pressures, protein, and glucose. India ink stain is negative for Cryptococcus neoformans, but 1 week later CSF cultures are positive for Cryptococcus. The patient has a CD4 count of 15 and a viral load of approximately 44,000.

In patients with HIV, CD4 count can reveal the degree of immunocompromise, whereas viral load shows the extent of viral activity. Typically, patients with a CD4 count >500 are not at risk for opportunistic infections. A count

Box

Carefully evaluate patients with a CD4 count

Strongly consider ordering the RPR test for syphilis because:

 

• HIV and syphilis share sexual risk factors
  
• having syphilis increases the likelihood of comorbid HIV infection 7- to 9-fold¹¹
  
• syphilis may worsen the course of HIV infection¹²
  
• syphilis can mimic psychiatric symptoms.^13,14
  

CSF analysis may reveal evidence of meningitis, and special stains may be used to detect meningitis-causing organisms that are characteristic of AIDS. CSF also may be tested directly for CNS syphilis.

STEP 3 Order neuroimaging

Neuroimaging is an essential part of the workup of a patient for whom your clinical examination raises suspicion for CNS impairment. In patients with longstanding HIV infection, brain imaging may reveal cerebral atrophy, which may accompany the cognitive changes found in HIV-associated dementia. In addition, immunocompromised patients, particularly those with a CD4 count 15

CASE CONTINUED

Brain MRI shows moderate cerebral and cerebellar atrophy, which ID clinicians attribute to the long-term effects of HIV infection. No evidence of focal or mass lesions is seen.

By further investigating Mr. G’s medical records, you find a brain MRI performed when Mr. G initially presented with toxoplasmosis in 2001. This scan reveals a large ring-enhancing mass in the right frontal lobe. Although the patient had refused a brain biopsy, the radiologist determined the lesion was most consistent in appearance with intracranial toxoplasmosis.

STEP 4 Perform neuropsychological testing

When physical exam, mental status exam, or neuroimaging suggests a possible CNS cause for a patient’s psychiatric presentation, neuropsychological testing can help characterize which of the patient’s brain functions are compromised and determine their anatomic source. This testing allows for a more complete and precise assessment of brain function than can be achieved by a bedside cognitive exam. It typically includes the Trail Making Test Parts A and B and the Grooved Pegboard Test to evaluate executive and psychomotor functioning, as well as the Controlled Oral Word Association Test to evaluate cognitive speed.

CASE CONTINUED

A search of medical records reveals that Mr. G had recently undergone a brief neuropsychological assessment at the hospital’s outpatient HIV mental health clinic. The psychologist found evidence of frontal lobe dysfunction, including problems with shifting sets, verbal fluency, and naming the months of the year backwards. Mr. G’s performance demonstrated a subcortical dementia pattern that included prominent fine motor impairment.

In HIV-positive patients with evidence of cognitive impairment, neuropsychological testing can help determine if the pattern of deficits is consistent with HIV-associated dementia. Such deficits typically follow the pattern of a subcortical dementia characterized by apathy, amotivation, psychomotor retardation, and slowing of general information processing. This differentiates it from Alzheimer’s dementia, which is typically characterized by shortterm memory impairment, personality changes, and affective changes such as depression.

STEP 5 Synthesize all data to make a diagnosis

Psychiatric illness in HIV-positive patients may involve factors at multiple biopsychosocial levels, including problems with social support, psychological stress, primary psychiatric illness, immunocompromise, and CNS disease. Consider data from all of these levels to arrive at a diagnosis.

CASE CONTINUED

After carefully considering Mr. G’s history, physical and mental status examinations, laboratory data, current and past neuroimaging, and neuropsychological testing, you and ID clinicians conclude that Mr. G’s neuropsychiatric presentation primarily represents the residual deficits from his large frontal lobe toxoplasmosis lesion diagnosed in 2001, with possible contribution from an underlying HIV-associated dementia. You feel that a depressive disorder can be ruled out with a high degree of certainty because the patient denied abnormalities of mood or hedonic tone, did not demonstrate deficits in neurovegetative functioning such as appetite, energy, and sleep, and did not show evidence of suicidality. You attribute the flat affect and amotivation that had prompted the psychiatric consult to his secondary neuropsychiatric deficits.

In the absence of another neurologic diagnosis, Mr. G would likely be classified as having Stage 1 HIV-associated dementia. (Table 3).^9,16 However, it is difficult to determine which of his deficits are due to an underlying HIV-related dementing process and which are related to his more focal frontal lobe compromise demonstrated on neuropsychological testing.

Table 3

Staging system for HIV-associated dementia

Stage	Degree of severity	Clinical characteristics
0	Normal	Normal mental and motor function
0.5	Equivocal	Minimal or equivocal symptoms characteristic of cognitive or motor dysfunction, or mild signs (snout response or slowed extremity movements); no impairment of work or ADLs; gait and strength normal
1	Mild	Unequivocal evidence of functional, intellectual, or motor impairment (including symptoms, signs, or neuropsychological testing); can walk without assistance and perform all except more demanding aspects of work or ADLs
2	Moderate	Able to perform basic activities of self care but unable to work or maintain the more demanding ADLs; ambulatory but may require a single prop
3	Severe	Major intellectual incapacity (cannot follow news or personal events, cannot sustain complex conversation, considerable slowing of all outputs) or motor disability (unable to walk unassisted, requires walker or personal support, usually slowed and accompanied by clumsiness of arms)
4	End stage	A nearly vegetative state; intellectual and social comprehension and output are rudimentary; patient is nearly or absolutely mute and paraparetic or paraplegic, with urinary and fecal incontinence
ADLs: activities of daily living
Source: References 9,16

 

CASE CONTINUED

Because Mr. G had no evidence of a mood syndrome, you do not recommend antidepressants. You note that although a stimulant might improve the patient’s cognitive function and apathy, Mr. G’s history of heavy cocaine use is considered a contraindication.

Mr. G’s cognitive and motivation deficits will complicate the management of his complex medical condition and medications. You recommend that he be referred to a structured outpatient living and care environment to support his HAART adherence. Despite the primary team’s efforts in discharge planning, however, the patient does not keep his clinic appointments and is lost to follow-up.

Related Resources

• Aidsmap information on AIDS and HIV. www.aidsmap.com.
  
• America Psychiatric Association AIDS Resource Center. www.psych.org/AIDS.
  

Drug brand names

• Abacavir • Ziagen
  
• Amprenavir • Agenerase
  
• Didanosine • Videx
  
• Efavirenz • Sustiva
  
• Enfuvirtide • Fuzeon
  
• Indinavir • Crixivan
  
• Lamivudine • Epivir
  
• Lopinavir/Ritonavir • Kaletra
  
• Nevirapine • Viramune
  
• Pyrimethamine • Daraprim
  
• Ritonavir • Norvir
  
• Saquinavir • Invirase
  
• Stavudine • Zerit
  
• Sulfadiazine • Microsulfon
  
• Zalcitabine • Hivid
  
• Zidovudine • Retrovir
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Mr. G, a 28-year-old heterosexual Puerto Rican man, is admitted to the hospital’s infectious diseases (ID) unit after 3 weeks of worsening bifrontal headaches. He has been treated as an outpatient for several years since becoming HIV-positive and was diagnosed with AIDS after an intracranial toxoplasmosis infection. Although he has not taken antiretrovirals for several months, Mr. G has adhered intermittently to his antiretroviral regimen and previously developed other opportunistic infections, including thrush and bacterial pneumonia.

Three days after Mr. G is admitted, ID clinicians become concerned that he appears severely depressed and request a psychiatric evaluation.

Psychiatric evaluation and diagnosis in patients with HIV can be a challenge because of:

• the myriad ways HIV can impact the CNS
  
• the proliferation of antiretroviral medications
  
• patients’ increasing lifespan as a result of highly active antiretroviral therapy (HAART)¹
  
• the psychological repercussions of living with HIV infection.
  

In this case-based review, we outline a rational, 5-step approach to evaluating and diagnosing psychiatric symptoms in patients with HIV.

A wide differential diagnosis

Patients who are HIV-positive have disproportionately high rates of psychiatric disorders. One study of approximately 2,800 adults receiving care for HIV found that nearly one-half screened positive for major depression, dysthymia, generalized anxiety disorders, or panic attacks.² Some psychiatric morbidity may be related to:

• the stress of having HIV
  
• stressors related to risk factors for acquiring HIV, including low socioeconomic status, homelessness, and discrimination and social stigma based on race and sexual orientation
  
• substance abuse, which is common among patients with HIV.²
  

Other “psychiatric” symptoms may be the result of HIV infection in the brain, either acutely (as seen in HIV encephalopathy³) or cumulatively (as seen in AIDS-associated dementia⁴). Psychiatric symptoms may be the result of intracranial opportunistic infections in immunocompromised AIDS patients (Table 1).^5-8 Antiretroviral medications commonly used to treat HIV also can cause psychiatric symptoms (Table 2).^9,10

Because of the range and variety of psychopathology encountered in HIV disease, keep a wide differential diagnosis in mind when evaluating patients with HIV.

A 5-step process can help you determine if symptoms in any patient—regardless of HIV status—are caused by a primary psychiatric disorder or CNS impairment (Box).

Table 1

HIV-associated CNS infections

More common
Cryptococcus neoformans meningitis
Progressive multifocal leukoencephalopathy (polyomavirus JC)
Toxoplasma gondii
Less common
Aspergillosis
Coccidioidomycosis
Cytomegalovirus
Herpes simplex or varicella-zoster encephalitis
Histoplasmosis
Leptomeningeal tuberculosis
Source: References 5-8

Table 2

Neuropsychiatric side effects of antiretroviral medications

Medication	Potential side effect(s)
Abacavir	Depression, anxiety, psychosis
Amprenavir	Mood changes
Didanosine	Lethargy, nervousness, anxiety, confusion, sleep disturbances, mood disorders, psychosis
Efavirenz	Agitation, depersonalization, hallucinations, disturbed dreams, mood disorders, depression, suicidality, antisocial behavior, psychosis, catatonia, delirium
Enfuvirtide	Anxiety, depression
Indinavir	Mood changes
Lamivudine	Insomnia, mood disorders
Lopinavir+Ritonavir	Mood changes, agitation, anxiety
Nevirapine	Depression, cognitive impairment, psychosis
Ritonavir	Anxiety
Saquinavir	Depression, anxiety, sleep disturbances
Stavudine	Sleep disorders, mood disorders, delirium
Zalcitabine	Somnolence, impaired concentration, mood disorders, delirium
Zidovudine	Sleep disturbance, vivid dreams, agitation, mania, depression, psychotic symptoms, delirium
Source: References 9,10

STEP 1 Perform initial exams

A careful diagnostic exam that includes a mental status examination with gross cognitive functioning testing is necessary to differentiate primary psychiatric disorders from HIV-related CNS pathology, including:

• HIV-associated dementia
  
• HIV-associated minor cognitive motor disorder (a less severe form of HIV-related cognitive and psychomotor impairment)
  
• opportunistic infections.
  

CASE CONTINUED

Mr. G sits in a chair alone in his room, looking out the window. He responds minimally to your initial greetings and has a staring expression and flat affect. Mr. G is calm and cooperative with the exam but has almost no spontaneous speech, answering questions with slow, imprecise 3- or 4-word responses. He is relaxed and does not seem guarded or paranoid.

Mr. G denies depressed mood or suicidal thinking and appears surprised to be asked about these symptoms. He also denies a history of manic or psychotic symptoms or problems with sleep, appetite, or energy. Bedside cognitive exam—focusing on alertness, orientation, attention, and memory—does not demonstrate any gross deficits.

Cognitive workup. Be vigilant for deficits in attention and orientation that might indicate an acute brain syndrome. In addition, look for discrepant patterns of symptoms or other features that may suggest CNS pathology. For example, Mr. G’s impoverished speech and lack of motivation—combined with a clear sensorium and lack of obvious patterns of mood, anxiety, or psychotic symptoms—suggest that a primary psychiatric disorder might not explain his presentation.

Although commonly used, the bedside Mini-Mental State Examination may be insensitive to cognitive deficits in HIV-associated dementia. The HIV-Dementia Scale is more sensitive to HIV’s typical subcortical features.

Physical workup. When evaluating symptoms in an immunocompromised patient at risk for opportunistic infections, it is important to conduct a comprehensive physical exam. Pay attention to evidence of secondary infection and to neurologic signs. Fever may suggest an opportunistic infection that could contribute to psychiatric symptoms. Immunocompromise in HIV may be associated with a variety of infectious meningitis forms, such as:

 

• cryptococcus
  
• aseptic meningitis (which may be caused by HIV)
  
• histoplasmosis
  
• coccidioidomycosis.
  

A stiff neck or positive Kernig’s and Brudzinski’s signs (pain elicited upon passive extension of the knee with the hip flexed, or with flexion of the neck) specifically indicate an infection or other inflammatory process within the meninges that may lead to mental status changes. Motor, sensory, and cranial nerve examinations can detect evidence of intracranial mass lesions resulting from CNS neoplasms or infections to which immunocompromised patients are vulnerable.

CASE CONTINUED

Physical exam reveals that Mr. G has a low-grade fever (100.2° F) and penile erosion consistent with herpes simplex infection. He has no meningeal signs and an otherwise normal neurologic examination.

STEP 2 Evaluate lab results

Use laboratory testing to search for potential medical causes of the patient’s presentation. Include a complete blood cell count, electrolytes, blood urea nitrogen and creatinine, and liver function tests to look for underlying metabolic problems.

CASE CONTINUED

Complete blood count, electrolytes, kidney function, and liver function tests are all within normal limits, and rapid plasma reagin (RPR) for syphilis is negative. Cerebrospinal fluid (CSF) analysis demonstrates normal opening pressures, protein, and glucose. India ink stain is negative for Cryptococcus neoformans, but 1 week later CSF cultures are positive for Cryptococcus. The patient has a CD4 count of 15 and a viral load of approximately 44,000.

In patients with HIV, CD4 count can reveal the degree of immunocompromise, whereas viral load shows the extent of viral activity. Typically, patients with a CD4 count >500 are not at risk for opportunistic infections. A count

Box

Carefully evaluate patients with a CD4 count

Strongly consider ordering the RPR test for syphilis because:

 

• HIV and syphilis share sexual risk factors
  
• having syphilis increases the likelihood of comorbid HIV infection 7- to 9-fold¹¹
  
• syphilis may worsen the course of HIV infection¹²
  
• syphilis can mimic psychiatric symptoms.^13,14
  

CSF analysis may reveal evidence of meningitis, and special stains may be used to detect meningitis-causing organisms that are characteristic of AIDS. CSF also may be tested directly for CNS syphilis.

STEP 3 Order neuroimaging

Neuroimaging is an essential part of the workup of a patient for whom your clinical examination raises suspicion for CNS impairment. In patients with longstanding HIV infection, brain imaging may reveal cerebral atrophy, which may accompany the cognitive changes found in HIV-associated dementia. In addition, immunocompromised patients, particularly those with a CD4 count 15

CASE CONTINUED

Brain MRI shows moderate cerebral and cerebellar atrophy, which ID clinicians attribute to the long-term effects of HIV infection. No evidence of focal or mass lesions is seen.

By further investigating Mr. G’s medical records, you find a brain MRI performed when Mr. G initially presented with toxoplasmosis in 2001. This scan reveals a large ring-enhancing mass in the right frontal lobe. Although the patient had refused a brain biopsy, the radiologist determined the lesion was most consistent in appearance with intracranial toxoplasmosis.

STEP 4 Perform neuropsychological testing

When physical exam, mental status exam, or neuroimaging suggests a possible CNS cause for a patient’s psychiatric presentation, neuropsychological testing can help characterize which of the patient’s brain functions are compromised and determine their anatomic source. This testing allows for a more complete and precise assessment of brain function than can be achieved by a bedside cognitive exam. It typically includes the Trail Making Test Parts A and B and the Grooved Pegboard Test to evaluate executive and psychomotor functioning, as well as the Controlled Oral Word Association Test to evaluate cognitive speed.

CASE CONTINUED

A search of medical records reveals that Mr. G had recently undergone a brief neuropsychological assessment at the hospital’s outpatient HIV mental health clinic. The psychologist found evidence of frontal lobe dysfunction, including problems with shifting sets, verbal fluency, and naming the months of the year backwards. Mr. G’s performance demonstrated a subcortical dementia pattern that included prominent fine motor impairment.

In HIV-positive patients with evidence of cognitive impairment, neuropsychological testing can help determine if the pattern of deficits is consistent with HIV-associated dementia. Such deficits typically follow the pattern of a subcortical dementia characterized by apathy, amotivation, psychomotor retardation, and slowing of general information processing. This differentiates it from Alzheimer’s dementia, which is typically characterized by shortterm memory impairment, personality changes, and affective changes such as depression.

STEP 5 Synthesize all data to make a diagnosis

Psychiatric illness in HIV-positive patients may involve factors at multiple biopsychosocial levels, including problems with social support, psychological stress, primary psychiatric illness, immunocompromise, and CNS disease. Consider data from all of these levels to arrive at a diagnosis.

CASE CONTINUED

After carefully considering Mr. G’s history, physical and mental status examinations, laboratory data, current and past neuroimaging, and neuropsychological testing, you and ID clinicians conclude that Mr. G’s neuropsychiatric presentation primarily represents the residual deficits from his large frontal lobe toxoplasmosis lesion diagnosed in 2001, with possible contribution from an underlying HIV-associated dementia. You feel that a depressive disorder can be ruled out with a high degree of certainty because the patient denied abnormalities of mood or hedonic tone, did not demonstrate deficits in neurovegetative functioning such as appetite, energy, and sleep, and did not show evidence of suicidality. You attribute the flat affect and amotivation that had prompted the psychiatric consult to his secondary neuropsychiatric deficits.

In the absence of another neurologic diagnosis, Mr. G would likely be classified as having Stage 1 HIV-associated dementia. (Table 3).^9,16 However, it is difficult to determine which of his deficits are due to an underlying HIV-related dementing process and which are related to his more focal frontal lobe compromise demonstrated on neuropsychological testing.

Table 3

Staging system for HIV-associated dementia

Stage	Degree of severity	Clinical characteristics
0	Normal	Normal mental and motor function
0.5	Equivocal	Minimal or equivocal symptoms characteristic of cognitive or motor dysfunction, or mild signs (snout response or slowed extremity movements); no impairment of work or ADLs; gait and strength normal
1	Mild	Unequivocal evidence of functional, intellectual, or motor impairment (including symptoms, signs, or neuropsychological testing); can walk without assistance and perform all except more demanding aspects of work or ADLs
2	Moderate	Able to perform basic activities of self care but unable to work or maintain the more demanding ADLs; ambulatory but may require a single prop
3	Severe	Major intellectual incapacity (cannot follow news or personal events, cannot sustain complex conversation, considerable slowing of all outputs) or motor disability (unable to walk unassisted, requires walker or personal support, usually slowed and accompanied by clumsiness of arms)
4	End stage	A nearly vegetative state; intellectual and social comprehension and output are rudimentary; patient is nearly or absolutely mute and paraparetic or paraplegic, with urinary and fecal incontinence
ADLs: activities of daily living
Source: References 9,16

 

CASE CONTINUED

Because Mr. G had no evidence of a mood syndrome, you do not recommend antidepressants. You note that although a stimulant might improve the patient’s cognitive function and apathy, Mr. G’s history of heavy cocaine use is considered a contraindication.

Mr. G’s cognitive and motivation deficits will complicate the management of his complex medical condition and medications. You recommend that he be referred to a structured outpatient living and care environment to support his HAART adherence. Despite the primary team’s efforts in discharge planning, however, the patient does not keep his clinic appointments and is lost to follow-up.

Related Resources

• Aidsmap information on AIDS and HIV. www.aidsmap.com.
  
• America Psychiatric Association AIDS Resource Center. www.psych.org/AIDS.
  

Drug brand names

• Abacavir • Ziagen
  
• Amprenavir • Agenerase
  
• Didanosine • Videx
  
• Efavirenz • Sustiva
  
• Enfuvirtide • Fuzeon
  
• Indinavir • Crixivan
  
• Lamivudine • Epivir
  
• Lopinavir/Ritonavir • Kaletra
  
• Nevirapine • Viramune
  
• Pyrimethamine • Daraprim
  
• Ritonavir • Norvir
  
• Saquinavir • Invirase
  
• Stavudine • Zerit
  
• Sulfadiazine • Microsulfon
  
• Zalcitabine • Hivid
  
• Zidovudine • Retrovir
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

Antidepressants
Trazodone and, in rare cases, phenelzine and sertraline; bupropion has been associated with clitoral priapism3
Antihypertensives that act via alpha blockade Labetalol, prazosin3-5
Metoclopramide when taken with thioridazine3,4
Sildenafil citrate6 (rare case reports)
Substances of abuse
Alcohol, marijuana, crack cocaine
Typical and atypical antipsychotics
Chlorpromazine, clozapine, fluphenazine, haloperidol, mesoridazine, molindone, levomepromazine, perphenazine, promazine, risperidone, thioridazine, thiothixene3-5

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

 

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Carcinoma of the bladder or prostate Diabetic neuropathy Fabray’s disease (genetic disorder that causes heart, kidney, and brain damage) Blood disorders, including leukemia, thrombocytopenia, sickle cell disease, thalassemia, polycythemia Lymphomas Malignancies, particularly when a tumor has infiltrated the penis Mumps Spinal cord trauma Prostatitis Rocky Mountain spotted fever

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

 

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

Dr. Freed reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

Antidepressants
Trazodone and, in rare cases, phenelzine and sertraline; bupropion has been associated with clitoral priapism3
Antihypertensives that act via alpha blockade Labetalol, prazosin3-5
Metoclopramide when taken with thioridazine3,4
Sildenafil citrate6 (rare case reports)
Substances of abuse
Alcohol, marijuana, crack cocaine
Typical and atypical antipsychotics
Chlorpromazine, clozapine, fluphenazine, haloperidol, mesoridazine, molindone, levomepromazine, perphenazine, promazine, risperidone, thioridazine, thiothixene3-5

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

 

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Carcinoma of the bladder or prostate Diabetic neuropathy Fabray’s disease (genetic disorder that causes heart, kidney, and brain damage) Blood disorders, including leukemia, thrombocytopenia, sickle cell disease, thalassemia, polycythemia Lymphomas Malignancies, particularly when a tumor has infiltrated the penis Mumps Spinal cord trauma Prostatitis Rocky Mountain spotted fever

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

 

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

Dr. Freed reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

Antidepressants
Trazodone and, in rare cases, phenelzine and sertraline; bupropion has been associated with clitoral priapism3
Antihypertensives that act via alpha blockade Labetalol, prazosin3-5
Metoclopramide when taken with thioridazine3,4
Sildenafil citrate6 (rare case reports)
Substances of abuse
Alcohol, marijuana, crack cocaine
Typical and atypical antipsychotics
Chlorpromazine, clozapine, fluphenazine, haloperidol, mesoridazine, molindone, levomepromazine, perphenazine, promazine, risperidone, thioridazine, thiothixene3-5

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

 

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Carcinoma of the bladder or prostate Diabetic neuropathy Fabray’s disease (genetic disorder that causes heart, kidney, and brain damage) Blood disorders, including leukemia, thrombocytopenia, sickle cell disease, thalassemia, polycythemia Lymphomas Malignancies, particularly when a tumor has infiltrated the penis Mumps Spinal cord trauma Prostatitis Rocky Mountain spotted fever

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

 

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

Dr. Freed reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.