A cry for help: Treating involuntary emotional expression disorder

Mrs. R, a 68-year-old retired teacher, is referred to you for suspected mania after a closed head injury from a car accident. The referring physician reports that Mrs. R experienced mild anterograde amnesia that has resolved, but she continues to suffer from “persistent mood swings as evidenced by substantial inappropriate laughter.”

Mrs. R is not manic. Her mood is normal, with a relatively euthymic affect. When asked about her accident or injury, however, she breaks into bouts of laughter that appear to be uncontrollable and last up to several minutes. These episodes include respiratory changes that make her laughter nearly indistinguishable from crying. Mrs. R explains that the episodes occur every time she discusses the accident—regardless of her efforts to prevent them—and complains they are extremely frustrating and embarrassing. She avoids situations that might trigger the episodes.

Patients with involuntary emotional expression disorder (IEED)—a neurologic disorder that manifests as brief bouts of uncontrollable crying, laughing, or both—may appear to have bipolar disorder, schizophrenia, depression, or another psychiatric disorder. Careful evaluation, however, can distinguish IEED from other conditions. Managing the disorder requires an understanding of IEED phenomenology, including:

• neurologic conditions that result in IEED
  
• underlying pathology
  
• diagnostic criteria
  
• effective treatments.
  

Brain dysfunction alters affect

IEED was introduced as an inclusive term, replacing previous nomenclature such as pathologic laughing and crying, pseudobulbar affect, affective lability, and emotional incontinence.¹

IEED can present as episodes of laughter, as in Mrs. R’s case, but more commonly manifests as bouts of crying. Other presentations include a combination of laughing and crying, but episodic outbursts of other emotions that are out of the patient’s control—such as anger—can be included in this syndrome.² IEED episodes can lead to embarrassment, frustration, and anger that eventually can affect mood and often cause patients to avoid social interaction.³

IEED can occur in any condition that damages and affects the brain areas critical to emotional motor output (Box 1).^4-6 The broad pattern of lesions that can result in IEED stems from many disease states. IEED is often observed in amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury. It also may occur in dementia, Parkinson’s disease, and other disorders (Table 1).⁷

Table 1

Neurologic conditions associated with IEED

Amyotrophic lateral sclerosis
Multiple sclerosis
Traumatic brain injury
Stroke
Alzheimer’s disease
Frontotemporal dementia
Parkinson’s disease
Progressive supranuclear palsy
Multiple systems atrophy
Wilson’s disease
Normal pressure hydrocephalus
Olivopontine cerebellar atrophy
Source: Reference 7

Diagnosis can be elusive

Although IEED is not included in DSM-IV-TR, recently developed diagnostic criteria can help distinguish it from other disorders (Table 2).¹ As with DSM-categorized disorders, IEED must result in clinically significant distress or impairment in social or occupational function and must not be better accounted for by another disorder or caused by a physiologic substance.

The patient must present with symptoms caused by brain dysfunction from brain injury or neurodegenerative disease. Underlying brain damage might not be apparent when the patient first presents, but to our knowledge no case of idiopathic IEED has been described. If a patient presents with symptoms thought to be IEED, first determine what underlying neurologic condition is causing the symptoms and optimally manage this disorder.

To be considered IEED, the patient’s symptoms must represent a change from his or her normal emotional reactivity. When interviewing patients and their families, compare the patient’s current emotional reactivity with that from when he or she was free of all disease symptoms. Such considerations are important because a patient may have a life-long condition in which he or she is prone to emotional displays—such as essential crying—that is distinct from IEED.⁸

Symptoms must be incongruent with or in excess of the person’s underlying mood and independent or in excess of the provoking stimulus. Inappropriateness of the emotional response is the hallmark of IEED.

IEED episodes have characteristic clinical features (Table 3). They are brief—lasting seconds to minutes—and sudden in onset and conclusion. Episodes are likely to be stereotyped in severity and presenting type within patients, as well as in the triggering stimulus or set of stimuli. For example, patients often experience episodes when asked about the syndrome.⁹ In severe cases, patients experience episodes with any interpersonal contact.¹⁰

Some characteristics support—but are not essential for—an IEED diagnosis:

• autonomic symptoms, such as flushing of the face and increased salivary production during episodes
  
• pseudobulbar signs, such as increased jaw jerk, exaggerated gag reflex, dysarthria, and dysphagia
  
• other emotional outbursts.
  

 

Table 2

Is it IEED? Diagnostic criteria

Presence of brain damage
Episodes of involuntary emotional motor output that: represent a change from normal emotional reactivity are independent or in excess of provoking stimuli result in clinically significant distress or social or functional impairment
Disorder is not: better accounted for by another neurologic or psychiatric disorder caused by a physiologic substance
Source: Reference 1

Table 3

Characteristics of IEED episodes

Paroxysmal, sudden onset with rapid offset
Brief (up to several minutes)
Stereotyped across patients (may manifest in similar fashion from patient to patient)
Stereotyped within patients (episodes often have similar type, severity, and eliciting stimuli)

Box 1

CASE CONTINUED: Reaching a diagnosis

After thoroughly interviewing Mrs. R, you exclude mood disorders such as depression or bipolar disorder. The paroxysmal, episodic nature of her emotional outbursts and the consistency of the eliciting stimulus, suggest IEED.

Distinguishing IEED from depression. Physicians may be quick to diagnose a patient with consistent, recurrent crying as having a depressive disorder. In IEED, the patient’s family commonly (and inappropriately) will confirm this misperception, even if the patient claims otherwise. The hallmark distinctions between depression and IEED are:

• duration of crying
  
• associated mood state.
  

Major depressive disorder (MDD) is a persistent change in a patient’s mood lasting weeks to months, accompanied by feelings of guilt, helplessness, hopelessness, and worthlessness, apathy, and anhedonia.¹¹ IEED is paroxysmal, with uncontrollable changes in affect without a corresponding sudden mood change. Patients may report mood changes during episodes, but between episodes return to an euthymic affect.

Patients who suffer from MDD, however, are not excluded from an IEED diagnosis. In 1 small study, almost one-half of patients with IEED also had major depression.¹² Differentiating these syndromes—even in patients who suffer from both—is important to ensure proper management and patient and family understanding of the condition. Lastly, although IEED is not a mood disorder, the embarrassment and frustration it causes can change a patient’s mood over time.

Recommended treatment

Education. In our experience, education is critical to help patients and family members understand IEED and deal with embarrassment and other normal reactions they may experience. Explain that these emotional displays are not manic or psychotic episodes but periods of motor dyscontrol caused by a neurologic condition.

Teach them to cope with IEED by:

• identifying and avoiding stimuli that provoke IEED episodes
  
• ignoring the episodes and continuing with usual activities.
  

Antidepressants are first-line pharmacotherapy for IEED. Studies and case reports have shown efficacy for tricyclic antidepressants (TCAs) such as nortriptyline and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Table 4).^2,12-16

These agents have IEED-specific therapeutic effects through a mechanism independent of their antidepressant action. In patients with IEED and depression, antidepressants may resolve IEED while depression remains refractory.^2,12 Potential drawbacks include anticholinergic effects with TCAs and sexual and gastrointestinal side effects with SSRIs. Nevertheless, these agents are the optimal first-line therapy for IEED among currently available options.

Other agents. Small studies have investigated other agents, but the data are insufficient to warrant recommendations for clinical practice. One study found that the novel antidepressant mirtazapine improved symptoms in 2 patients who did not respond to SSRIs.¹⁷ In another study, levodopa therapy resulted in improvement in 10 of 25 patients.¹⁸

Box 2

 

A combination dextromethorphan and quinidine (DM/Q) is being evaluated for IEED. This compound has demonstrated efficacy in IEED patients with ALS¹⁹ and MS²⁰ and is in Phase III clinical development. DM/Q is thought to be a potent activator of the sigma-1 receptor system as well as an N-methyl-D-aspartate antagonist.²¹

Table 4

IEED: Evidence for antidepressants

Drug	Study design/population	Dosage	Outcome
Tricyclics
Amitriptyline	Schiffer et al;13 double-blind crossover; 12 multiple sclerosis patients	Mean: 57.8 mg/d	8 patients showed significant improvement compared with placebo
Nortriptyline	Robinson et al;12 double-blind, placebo-controlled; 28 stroke patients	≤100 mg/d	Patients receiving nortriptyline reported significantly greater improvement on PLACS at 4 and 6 weeks compared with placebo
Selective serotonin reuptake inhibitors
Citalopram	Anderson et al;14 double-blind, placebo-controlled crossover; 16 stroke patients	10 to 20 mg/d	Citalopram decreased the number of daily crying episodes by ≥50% compared with placebo
Fluoxetine	Choi-Kwon et al;2 double-blind placebo-controlled; 152 patients	20 mg/d	Fluoxetine significantly improved measures of IEED and anger proneness but not depression
Paroxetine	Müller et al;15 consecutive case series, comparison with citalopram; 26 patients with traumatic brain injury or stroke	10 to 40 mg/d	Both paroxetine and citalopram resulted in significant improvements in measures of emotionalism
Sertraline	Burns et al;16 double-blind, placebo-controlled; 28 stroke patients	50 mg/d	Patients receiving sertraline had significant improvements in measures of emotionalism
IEED: involuntary emotional expression disorder; PLACS: Pathological Laughing and Crying Scale

CASE CONTINUED: Effective pharmacotherapy

After diagnosing IEED, you start Mrs. R on sertraline, 50 mg/d. She experiences a nearly immediate reduction in the number of daily IEED episodes. As a result, she feels more comfortable engaging in social activities.

Recommendations. We recommend using pharmacologic therapy for IEED. Because of the presence of underlying brain damage, IEED patients are likely to require treatment for other chronic or progressive conditions. Choose first-line therapy based on the patient’s medication regimen and comorbid conditions, as well as the drug’s side-effect profile.

Effective pharmacologic intervention can greatly improve patients’ quality of life.^19,20 Use scales that measure IEED severity to gauge treatment effectiveness (Box 2).^{12,19,20,22-25} Because treatment failure is a realistic possibility,¹⁷ you may need to try a variety of agents to determine which regimen provides the greatest efficacy and therapeutic effects.

Related Resources

• Involuntary emotional expressive disorder (for healthcare professionals). www.ieed.org/hp.
  
• Pathological laughing and crying scale (PLACS). Robinson RG, Parikh RM, Lipsey JR, et al. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry 1993;150:286-93.
  
• Center for neurologic study—lability scale (CNS-LS). Moore SR, Gresham LS, Bromberg MB, et al. A self report measure of affective lability. J Neurol Neurosurg Psychiatry 1997;63:89-93.
  

Drug brand names

• Amitriptyline • Elavil, Endep
  
• Citalopram • Celexa
  
• Dextromethorphan/quinidine • Zenvia*
  
• Fluoxetine • Prozac
  
• Levodopa • Larodopa
  
• Mirtazapine • Remeron
  
• Nortriptyline • Aventyl
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• * IN PHASE III DEVELOPMENT
  

Disclosures

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

Dr. Cummings is a consultant to Acadia Pharmaceuticals, Astellas Pharma, Avanir Pharmaceuticals, Cephalon, CoMentis, Eisai, Eli Lilly and Company, EnVivo Pharmaceuticals, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merck, Merz Pharma, Myriad, Neurochem, Novartis, Ono Pharmaceutical Co., Pfizer Inc., and sanofi-aventis. He is a speaker for Eisai, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merz Pharma, Novartis, and Pfizer Inc.

Mrs. R, a 68-year-old retired teacher, is referred to you for suspected mania after a closed head injury from a car accident. The referring physician reports that Mrs. R experienced mild anterograde amnesia that has resolved, but she continues to suffer from “persistent mood swings as evidenced by substantial inappropriate laughter.”

Mrs. R is not manic. Her mood is normal, with a relatively euthymic affect. When asked about her accident or injury, however, she breaks into bouts of laughter that appear to be uncontrollable and last up to several minutes. These episodes include respiratory changes that make her laughter nearly indistinguishable from crying. Mrs. R explains that the episodes occur every time she discusses the accident—regardless of her efforts to prevent them—and complains they are extremely frustrating and embarrassing. She avoids situations that might trigger the episodes.

Patients with involuntary emotional expression disorder (IEED)—a neurologic disorder that manifests as brief bouts of uncontrollable crying, laughing, or both—may appear to have bipolar disorder, schizophrenia, depression, or another psychiatric disorder. Careful evaluation, however, can distinguish IEED from other conditions. Managing the disorder requires an understanding of IEED phenomenology, including:

• neurologic conditions that result in IEED
  
• underlying pathology
  
• diagnostic criteria
  
• effective treatments.
  

Brain dysfunction alters affect

IEED was introduced as an inclusive term, replacing previous nomenclature such as pathologic laughing and crying, pseudobulbar affect, affective lability, and emotional incontinence.¹

IEED can present as episodes of laughter, as in Mrs. R’s case, but more commonly manifests as bouts of crying. Other presentations include a combination of laughing and crying, but episodic outbursts of other emotions that are out of the patient’s control—such as anger—can be included in this syndrome.² IEED episodes can lead to embarrassment, frustration, and anger that eventually can affect mood and often cause patients to avoid social interaction.³

IEED can occur in any condition that damages and affects the brain areas critical to emotional motor output (Box 1).^4-6 The broad pattern of lesions that can result in IEED stems from many disease states. IEED is often observed in amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury. It also may occur in dementia, Parkinson’s disease, and other disorders (Table 1).⁷

Table 1

Neurologic conditions associated with IEED

Amyotrophic lateral sclerosis
Multiple sclerosis
Traumatic brain injury
Stroke
Alzheimer’s disease
Frontotemporal dementia
Parkinson’s disease
Progressive supranuclear palsy
Multiple systems atrophy
Wilson’s disease
Normal pressure hydrocephalus
Olivopontine cerebellar atrophy
Source: Reference 7

Diagnosis can be elusive

Although IEED is not included in DSM-IV-TR, recently developed diagnostic criteria can help distinguish it from other disorders (Table 2).¹ As with DSM-categorized disorders, IEED must result in clinically significant distress or impairment in social or occupational function and must not be better accounted for by another disorder or caused by a physiologic substance.

The patient must present with symptoms caused by brain dysfunction from brain injury or neurodegenerative disease. Underlying brain damage might not be apparent when the patient first presents, but to our knowledge no case of idiopathic IEED has been described. If a patient presents with symptoms thought to be IEED, first determine what underlying neurologic condition is causing the symptoms and optimally manage this disorder.

To be considered IEED, the patient’s symptoms must represent a change from his or her normal emotional reactivity. When interviewing patients and their families, compare the patient’s current emotional reactivity with that from when he or she was free of all disease symptoms. Such considerations are important because a patient may have a life-long condition in which he or she is prone to emotional displays—such as essential crying—that is distinct from IEED.⁸

Symptoms must be incongruent with or in excess of the person’s underlying mood and independent or in excess of the provoking stimulus. Inappropriateness of the emotional response is the hallmark of IEED.

IEED episodes have characteristic clinical features (Table 3). They are brief—lasting seconds to minutes—and sudden in onset and conclusion. Episodes are likely to be stereotyped in severity and presenting type within patients, as well as in the triggering stimulus or set of stimuli. For example, patients often experience episodes when asked about the syndrome.⁹ In severe cases, patients experience episodes with any interpersonal contact.¹⁰

Some characteristics support—but are not essential for—an IEED diagnosis:

• autonomic symptoms, such as flushing of the face and increased salivary production during episodes
  
• pseudobulbar signs, such as increased jaw jerk, exaggerated gag reflex, dysarthria, and dysphagia
  
• other emotional outbursts.
  

 

Table 2

Is it IEED? Diagnostic criteria

Presence of brain damage
Episodes of involuntary emotional motor output that: represent a change from normal emotional reactivity are independent or in excess of provoking stimuli result in clinically significant distress or social or functional impairment
Disorder is not: better accounted for by another neurologic or psychiatric disorder caused by a physiologic substance
Source: Reference 1

Table 3

Characteristics of IEED episodes

Paroxysmal, sudden onset with rapid offset
Brief (up to several minutes)
Stereotyped across patients (may manifest in similar fashion from patient to patient)
Stereotyped within patients (episodes often have similar type, severity, and eliciting stimuli)

Box 1

CASE CONTINUED: Reaching a diagnosis

After thoroughly interviewing Mrs. R, you exclude mood disorders such as depression or bipolar disorder. The paroxysmal, episodic nature of her emotional outbursts and the consistency of the eliciting stimulus, suggest IEED.

Distinguishing IEED from depression. Physicians may be quick to diagnose a patient with consistent, recurrent crying as having a depressive disorder. In IEED, the patient’s family commonly (and inappropriately) will confirm this misperception, even if the patient claims otherwise. The hallmark distinctions between depression and IEED are:

• duration of crying
  
• associated mood state.
  

Major depressive disorder (MDD) is a persistent change in a patient’s mood lasting weeks to months, accompanied by feelings of guilt, helplessness, hopelessness, and worthlessness, apathy, and anhedonia.¹¹ IEED is paroxysmal, with uncontrollable changes in affect without a corresponding sudden mood change. Patients may report mood changes during episodes, but between episodes return to an euthymic affect.

Patients who suffer from MDD, however, are not excluded from an IEED diagnosis. In 1 small study, almost one-half of patients with IEED also had major depression.¹² Differentiating these syndromes—even in patients who suffer from both—is important to ensure proper management and patient and family understanding of the condition. Lastly, although IEED is not a mood disorder, the embarrassment and frustration it causes can change a patient’s mood over time.

Recommended treatment

Education. In our experience, education is critical to help patients and family members understand IEED and deal with embarrassment and other normal reactions they may experience. Explain that these emotional displays are not manic or psychotic episodes but periods of motor dyscontrol caused by a neurologic condition.

Teach them to cope with IEED by:

• identifying and avoiding stimuli that provoke IEED episodes
  
• ignoring the episodes and continuing with usual activities.
  

Antidepressants are first-line pharmacotherapy for IEED. Studies and case reports have shown efficacy for tricyclic antidepressants (TCAs) such as nortriptyline and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Table 4).^2,12-16

These agents have IEED-specific therapeutic effects through a mechanism independent of their antidepressant action. In patients with IEED and depression, antidepressants may resolve IEED while depression remains refractory.^2,12 Potential drawbacks include anticholinergic effects with TCAs and sexual and gastrointestinal side effects with SSRIs. Nevertheless, these agents are the optimal first-line therapy for IEED among currently available options.

Other agents. Small studies have investigated other agents, but the data are insufficient to warrant recommendations for clinical practice. One study found that the novel antidepressant mirtazapine improved symptoms in 2 patients who did not respond to SSRIs.¹⁷ In another study, levodopa therapy resulted in improvement in 10 of 25 patients.¹⁸

Box 2

 

A combination dextromethorphan and quinidine (DM/Q) is being evaluated for IEED. This compound has demonstrated efficacy in IEED patients with ALS¹⁹ and MS²⁰ and is in Phase III clinical development. DM/Q is thought to be a potent activator of the sigma-1 receptor system as well as an N-methyl-D-aspartate antagonist.²¹

Table 4

IEED: Evidence for antidepressants

Drug	Study design/population	Dosage	Outcome
Tricyclics
Amitriptyline	Schiffer et al;13 double-blind crossover; 12 multiple sclerosis patients	Mean: 57.8 mg/d	8 patients showed significant improvement compared with placebo
Nortriptyline	Robinson et al;12 double-blind, placebo-controlled; 28 stroke patients	≤100 mg/d	Patients receiving nortriptyline reported significantly greater improvement on PLACS at 4 and 6 weeks compared with placebo
Selective serotonin reuptake inhibitors
Citalopram	Anderson et al;14 double-blind, placebo-controlled crossover; 16 stroke patients	10 to 20 mg/d	Citalopram decreased the number of daily crying episodes by ≥50% compared with placebo
Fluoxetine	Choi-Kwon et al;2 double-blind placebo-controlled; 152 patients	20 mg/d	Fluoxetine significantly improved measures of IEED and anger proneness but not depression
Paroxetine	Müller et al;15 consecutive case series, comparison with citalopram; 26 patients with traumatic brain injury or stroke	10 to 40 mg/d	Both paroxetine and citalopram resulted in significant improvements in measures of emotionalism
Sertraline	Burns et al;16 double-blind, placebo-controlled; 28 stroke patients	50 mg/d	Patients receiving sertraline had significant improvements in measures of emotionalism
IEED: involuntary emotional expression disorder; PLACS: Pathological Laughing and Crying Scale

CASE CONTINUED: Effective pharmacotherapy

After diagnosing IEED, you start Mrs. R on sertraline, 50 mg/d. She experiences a nearly immediate reduction in the number of daily IEED episodes. As a result, she feels more comfortable engaging in social activities.

Recommendations. We recommend using pharmacologic therapy for IEED. Because of the presence of underlying brain damage, IEED patients are likely to require treatment for other chronic or progressive conditions. Choose first-line therapy based on the patient’s medication regimen and comorbid conditions, as well as the drug’s side-effect profile.

Effective pharmacologic intervention can greatly improve patients’ quality of life.^19,20 Use scales that measure IEED severity to gauge treatment effectiveness (Box 2).^{12,19,20,22-25} Because treatment failure is a realistic possibility,¹⁷ you may need to try a variety of agents to determine which regimen provides the greatest efficacy and therapeutic effects.

Related Resources

• Involuntary emotional expressive disorder (for healthcare professionals). www.ieed.org/hp.
  
• Pathological laughing and crying scale (PLACS). Robinson RG, Parikh RM, Lipsey JR, et al. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry 1993;150:286-93.
  
• Center for neurologic study—lability scale (CNS-LS). Moore SR, Gresham LS, Bromberg MB, et al. A self report measure of affective lability. J Neurol Neurosurg Psychiatry 1997;63:89-93.
  

Drug brand names

• Amitriptyline • Elavil, Endep
  
• Citalopram • Celexa
  
• Dextromethorphan/quinidine • Zenvia*
  
• Fluoxetine • Prozac
  
• Levodopa • Larodopa
  
• Mirtazapine • Remeron
  
• Nortriptyline • Aventyl
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• * IN PHASE III DEVELOPMENT
  

Disclosures

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

Dr. Cummings is a consultant to Acadia Pharmaceuticals, Astellas Pharma, Avanir Pharmaceuticals, Cephalon, CoMentis, Eisai, Eli Lilly and Company, EnVivo Pharmaceuticals, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merck, Merz Pharma, Myriad, Neurochem, Novartis, Ono Pharmaceutical Co., Pfizer Inc., and sanofi-aventis. He is a speaker for Eisai, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merz Pharma, Novartis, and Pfizer Inc.

Mrs. R, a 68-year-old retired teacher, is referred to you for suspected mania after a closed head injury from a car accident. The referring physician reports that Mrs. R experienced mild anterograde amnesia that has resolved, but she continues to suffer from “persistent mood swings as evidenced by substantial inappropriate laughter.”

Mrs. R is not manic. Her mood is normal, with a relatively euthymic affect. When asked about her accident or injury, however, she breaks into bouts of laughter that appear to be uncontrollable and last up to several minutes. These episodes include respiratory changes that make her laughter nearly indistinguishable from crying. Mrs. R explains that the episodes occur every time she discusses the accident—regardless of her efforts to prevent them—and complains they are extremely frustrating and embarrassing. She avoids situations that might trigger the episodes.

Patients with involuntary emotional expression disorder (IEED)—a neurologic disorder that manifests as brief bouts of uncontrollable crying, laughing, or both—may appear to have bipolar disorder, schizophrenia, depression, or another psychiatric disorder. Careful evaluation, however, can distinguish IEED from other conditions. Managing the disorder requires an understanding of IEED phenomenology, including:

• neurologic conditions that result in IEED
  
• underlying pathology
  
• diagnostic criteria
  
• effective treatments.
  

Brain dysfunction alters affect

IEED was introduced as an inclusive term, replacing previous nomenclature such as pathologic laughing and crying, pseudobulbar affect, affective lability, and emotional incontinence.¹

IEED can present as episodes of laughter, as in Mrs. R’s case, but more commonly manifests as bouts of crying. Other presentations include a combination of laughing and crying, but episodic outbursts of other emotions that are out of the patient’s control—such as anger—can be included in this syndrome.² IEED episodes can lead to embarrassment, frustration, and anger that eventually can affect mood and often cause patients to avoid social interaction.³

IEED can occur in any condition that damages and affects the brain areas critical to emotional motor output (Box 1).^4-6 The broad pattern of lesions that can result in IEED stems from many disease states. IEED is often observed in amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury. It also may occur in dementia, Parkinson’s disease, and other disorders (Table 1).⁷

Table 1

Neurologic conditions associated with IEED

Amyotrophic lateral sclerosis
Multiple sclerosis
Traumatic brain injury
Stroke
Alzheimer’s disease
Frontotemporal dementia
Parkinson’s disease
Progressive supranuclear palsy
Multiple systems atrophy
Wilson’s disease
Normal pressure hydrocephalus
Olivopontine cerebellar atrophy
Source: Reference 7

Diagnosis can be elusive

Although IEED is not included in DSM-IV-TR, recently developed diagnostic criteria can help distinguish it from other disorders (Table 2).¹ As with DSM-categorized disorders, IEED must result in clinically significant distress or impairment in social or occupational function and must not be better accounted for by another disorder or caused by a physiologic substance.

The patient must present with symptoms caused by brain dysfunction from brain injury or neurodegenerative disease. Underlying brain damage might not be apparent when the patient first presents, but to our knowledge no case of idiopathic IEED has been described. If a patient presents with symptoms thought to be IEED, first determine what underlying neurologic condition is causing the symptoms and optimally manage this disorder.

To be considered IEED, the patient’s symptoms must represent a change from his or her normal emotional reactivity. When interviewing patients and their families, compare the patient’s current emotional reactivity with that from when he or she was free of all disease symptoms. Such considerations are important because a patient may have a life-long condition in which he or she is prone to emotional displays—such as essential crying—that is distinct from IEED.⁸

Symptoms must be incongruent with or in excess of the person’s underlying mood and independent or in excess of the provoking stimulus. Inappropriateness of the emotional response is the hallmark of IEED.

IEED episodes have characteristic clinical features (Table 3). They are brief—lasting seconds to minutes—and sudden in onset and conclusion. Episodes are likely to be stereotyped in severity and presenting type within patients, as well as in the triggering stimulus or set of stimuli. For example, patients often experience episodes when asked about the syndrome.⁹ In severe cases, patients experience episodes with any interpersonal contact.¹⁰

Some characteristics support—but are not essential for—an IEED diagnosis:

• autonomic symptoms, such as flushing of the face and increased salivary production during episodes
  
• pseudobulbar signs, such as increased jaw jerk, exaggerated gag reflex, dysarthria, and dysphagia
  
• other emotional outbursts.
  

 

Table 2

Is it IEED? Diagnostic criteria

Presence of brain damage
Episodes of involuntary emotional motor output that: represent a change from normal emotional reactivity are independent or in excess of provoking stimuli result in clinically significant distress or social or functional impairment
Disorder is not: better accounted for by another neurologic or psychiatric disorder caused by a physiologic substance
Source: Reference 1

Table 3

Characteristics of IEED episodes

Paroxysmal, sudden onset with rapid offset
Brief (up to several minutes)
Stereotyped across patients (may manifest in similar fashion from patient to patient)
Stereotyped within patients (episodes often have similar type, severity, and eliciting stimuli)

Box 1

CASE CONTINUED: Reaching a diagnosis

After thoroughly interviewing Mrs. R, you exclude mood disorders such as depression or bipolar disorder. The paroxysmal, episodic nature of her emotional outbursts and the consistency of the eliciting stimulus, suggest IEED.

Distinguishing IEED from depression. Physicians may be quick to diagnose a patient with consistent, recurrent crying as having a depressive disorder. In IEED, the patient’s family commonly (and inappropriately) will confirm this misperception, even if the patient claims otherwise. The hallmark distinctions between depression and IEED are:

• duration of crying
  
• associated mood state.
  

Major depressive disorder (MDD) is a persistent change in a patient’s mood lasting weeks to months, accompanied by feelings of guilt, helplessness, hopelessness, and worthlessness, apathy, and anhedonia.¹¹ IEED is paroxysmal, with uncontrollable changes in affect without a corresponding sudden mood change. Patients may report mood changes during episodes, but between episodes return to an euthymic affect.

Patients who suffer from MDD, however, are not excluded from an IEED diagnosis. In 1 small study, almost one-half of patients with IEED also had major depression.¹² Differentiating these syndromes—even in patients who suffer from both—is important to ensure proper management and patient and family understanding of the condition. Lastly, although IEED is not a mood disorder, the embarrassment and frustration it causes can change a patient’s mood over time.

Recommended treatment

Education. In our experience, education is critical to help patients and family members understand IEED and deal with embarrassment and other normal reactions they may experience. Explain that these emotional displays are not manic or psychotic episodes but periods of motor dyscontrol caused by a neurologic condition.

Teach them to cope with IEED by:

• identifying and avoiding stimuli that provoke IEED episodes
  
• ignoring the episodes and continuing with usual activities.
  

Antidepressants are first-line pharmacotherapy for IEED. Studies and case reports have shown efficacy for tricyclic antidepressants (TCAs) such as nortriptyline and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Table 4).^2,12-16

These agents have IEED-specific therapeutic effects through a mechanism independent of their antidepressant action. In patients with IEED and depression, antidepressants may resolve IEED while depression remains refractory.^2,12 Potential drawbacks include anticholinergic effects with TCAs and sexual and gastrointestinal side effects with SSRIs. Nevertheless, these agents are the optimal first-line therapy for IEED among currently available options.

Other agents. Small studies have investigated other agents, but the data are insufficient to warrant recommendations for clinical practice. One study found that the novel antidepressant mirtazapine improved symptoms in 2 patients who did not respond to SSRIs.¹⁷ In another study, levodopa therapy resulted in improvement in 10 of 25 patients.¹⁸

Box 2

 

A combination dextromethorphan and quinidine (DM/Q) is being evaluated for IEED. This compound has demonstrated efficacy in IEED patients with ALS¹⁹ and MS²⁰ and is in Phase III clinical development. DM/Q is thought to be a potent activator of the sigma-1 receptor system as well as an N-methyl-D-aspartate antagonist.²¹

Table 4

IEED: Evidence for antidepressants

Drug	Study design/population	Dosage	Outcome
Tricyclics
Amitriptyline	Schiffer et al;13 double-blind crossover; 12 multiple sclerosis patients	Mean: 57.8 mg/d	8 patients showed significant improvement compared with placebo
Nortriptyline	Robinson et al;12 double-blind, placebo-controlled; 28 stroke patients	≤100 mg/d	Patients receiving nortriptyline reported significantly greater improvement on PLACS at 4 and 6 weeks compared with placebo
Selective serotonin reuptake inhibitors
Citalopram	Anderson et al;14 double-blind, placebo-controlled crossover; 16 stroke patients	10 to 20 mg/d	Citalopram decreased the number of daily crying episodes by ≥50% compared with placebo
Fluoxetine	Choi-Kwon et al;2 double-blind placebo-controlled; 152 patients	20 mg/d	Fluoxetine significantly improved measures of IEED and anger proneness but not depression
Paroxetine	Müller et al;15 consecutive case series, comparison with citalopram; 26 patients with traumatic brain injury or stroke	10 to 40 mg/d	Both paroxetine and citalopram resulted in significant improvements in measures of emotionalism
Sertraline	Burns et al;16 double-blind, placebo-controlled; 28 stroke patients	50 mg/d	Patients receiving sertraline had significant improvements in measures of emotionalism
IEED: involuntary emotional expression disorder; PLACS: Pathological Laughing and Crying Scale

CASE CONTINUED: Effective pharmacotherapy

After diagnosing IEED, you start Mrs. R on sertraline, 50 mg/d. She experiences a nearly immediate reduction in the number of daily IEED episodes. As a result, she feels more comfortable engaging in social activities.

Recommendations. We recommend using pharmacologic therapy for IEED. Because of the presence of underlying brain damage, IEED patients are likely to require treatment for other chronic or progressive conditions. Choose first-line therapy based on the patient’s medication regimen and comorbid conditions, as well as the drug’s side-effect profile.

Effective pharmacologic intervention can greatly improve patients’ quality of life.^19,20 Use scales that measure IEED severity to gauge treatment effectiveness (Box 2).^{12,19,20,22-25} Because treatment failure is a realistic possibility,¹⁷ you may need to try a variety of agents to determine which regimen provides the greatest efficacy and therapeutic effects.

Related Resources

• Involuntary emotional expressive disorder (for healthcare professionals). www.ieed.org/hp.
  
• Pathological laughing and crying scale (PLACS). Robinson RG, Parikh RM, Lipsey JR, et al. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry 1993;150:286-93.
  
• Center for neurologic study—lability scale (CNS-LS). Moore SR, Gresham LS, Bromberg MB, et al. A self report measure of affective lability. J Neurol Neurosurg Psychiatry 1997;63:89-93.
  

Drug brand names

• Amitriptyline • Elavil, Endep
  
• Citalopram • Celexa
  
• Dextromethorphan/quinidine • Zenvia*
  
• Fluoxetine • Prozac
  
• Levodopa • Larodopa
  
• Mirtazapine • Remeron
  
• Nortriptyline • Aventyl
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• * IN PHASE III DEVELOPMENT
  

Disclosures

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

Dr. Cummings is a consultant to Acadia Pharmaceuticals, Astellas Pharma, Avanir Pharmaceuticals, Cephalon, CoMentis, Eisai, Eli Lilly and Company, EnVivo Pharmaceuticals, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merck, Merz Pharma, Myriad, Neurochem, Novartis, Ono Pharmaceutical Co., Pfizer Inc., and sanofi-aventis. He is a speaker for Eisai, Forest Pharmaceuticals, Janssen, L.P., Lundbeck, Merz Pharma, Novartis, and Pfizer Inc.