Current Psychiatry

Mr. D, age 45, presents to his primary care physician with panic attacks, nausea, shortness of breath, nightmares, and dizziness 6 months after being assaulted and robbed at an ATM. Following a routine medical workup, the physician diagnoses posttraumatic stress disorder (PTSD) and refers Mr. D for exposure and response prevention therapy.

During graded exposure sessions, Mr. D’s eyes sometimes glaze over and he seems to “float away” from the discussion. When the therapist asks about these symptoms, Mr. D reports having had them as long as he can remember. In school, he says, teachers thought he was a slow learner, a daydreamer, or had attention-deficit/hyperactivity disorder. From what he can recall of his childhood, he describes a history of trauma and neglect with a violent, drug-abusing father and absent mother.

Patients with a history of early abuse or neglect are at risk for dissociative phenomena and other trauma-related psychiatric disorders.¹ The heterogeneous dissociative disorders are often hidden and unrecognized² —as in Mr. D’s case—or present with unfamiliar or atypical symptoms. Understanding and identifying dissociative symptoms is important because:

• Dissociative symptoms worsen prognosis, whether patients have conversion disorders¹ or psychogenic seizures³ or are in psychotherapy.⁴
  
• Dissociative states may impair memory encoding⁵ and decrease patients’ ability to remember therapeutic information.
  
• Symptoms (such as hearing voices in multiple personality disorder) can be confused with those of disorders with different treatment strategies (such as psychotic disorders).⁶
  
• Peritraumatic dissociation may be a risk factor for PTSD.⁷
  

This article presents a practical model for understanding dissociation, reviews clinical characteristics of this family of symptoms, and offers suggestions for assessing and treating patients with dissociative disorders.

Coming together, falling apart

Since Pierre Janet’s first reports on dissociative disorders, a number of theories and models of dissociation have been proposed,⁸ including empirically based, taxonomic models that address DSM-IV-TR categories (Table 1). The model I propose—which attaches a visual metaphor to dissociative phenomena—answers the question, “What is ‘dissociated’ in dissociation disorders?”

Table 1

DSM-IV-TR classification of dissociative disorders

Disorder	Symptoms
Dissociative amnesia	A reversible loss of memory, typically preceded by a stressor
Dissociative fugue	Loss of memory and identity, along with travel away from home
Dissociative identity disorder (formerly multiple personality disorder)	Presence of different identity states, often with lack of connection between them; current models highlight the presence of recurrent dissociative intrusions into many aspects of executive function and self
Depersonalization disorder	Detachment from oneself as a present, feeling person (depersonalization) and the world (derealization)
Dissociative identity disorder NOS	Functionally disturbing dissociative symptoms that do not fit into any of the above
NOS: not otherwise specified
Source: Diagnostic and statistical manual of mental disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

5 components of consciousness. Just as separable wavelengths compose a beam of white light, dissociable “colors” or components of subjective experience constitute a normal state of consciousness. Five implicit components of normal consciousness—present in various degrees, at different times—are seamlessly integrated and associated in real time.

One paired component is a detached “observer” and a more embodied, feeling “experiencer.” The observer is a perspective that begets metacognition (thinking about one’s inner world) and self-observation; it resides in the same body as soma-based “feelings” that unconsciously contribute to the sense of “being present” with oneself and the world in the moment.⁹

A second component is voluntary access to one’s autobiographical memories (memories about the self in time), which are constantly “updated” and integrated with current experiences. This component allows one to distinguish between remembered (past) experiences and “firsthand” (present) experience.

Three other components of normal consciousness are:

• a sense of agency and voluntary control over one’s mental contents, mental activity, and bodily movements
  
• an ongoing connection with one’s body and mind and an understanding of where sensations and images come from
  
• a sense of sequential experience, with relatively smooth transitions (from self at work to self at home, self a week ago to self today, etc) that have a singular referent (an identity).
  

Pathologic dissociation occurs when a prism of distress disperses one of these component “wavelengths” from the main “beam” of consciousness. For example:

• separation of the “observer” and “experiencer” occurs in depersonalization disorder
  
• reversible loss of ability to access memories characterizes dissociative amnesia
  
• disconnection between sequential experiences is a part of dissociative identity disorder.
  

This modular perspective of dissociative disorders parallels a neurophysiologic perspective of mental states as arising from the synchronized integration of the activity of separate, functionally specialized brain regions.

 

¹⁰ Functional neuroimaging of dissociation supports an understanding of these symptoms as “disconnection syndromes” (Box).

Box

Causes of dissociative disorders

As with many psychiatric disorders, the etiology of dissociative phenomena is thought to include the individual patient’s temperamental or constitutional predispositions¹¹ as well as a strong contribution of environmental trauma (early abuse, neglect).¹²

Constitutional predisposition for developing a dissociative disorder may include personality traits such as being easily hypnotized, mental absorption, suggestibility, and a tendency to fantasize.¹³ These characteristics fueled concerns in the 1990s that therapists may contribute to dissociative identity disorder by “digging” for repressed memories in susceptible patients and creating “pseudomemories” of events that did not happen.¹⁴

The issue of repressed traumatic memory and its role in therapy is extremely controversial and contributes to the complexity of psychotherapeutic treatment of dissociation.¹⁵

Early trauma. Factors that make it difficult to define the specific role of early trauma in dissociative disorders include:

• shame and secrecy of early sexual or physical abuse and potential for victims to repress traumatic memories
  
• lability of memory, potential for suggestibility, and difficulty with verification.¹⁴
  

Some experts—influenced by attachment theory—view dissociative phenomena as manifestations of an innate, reflexive relational pattern called disorganized attachment.¹⁶ Attachment theory notes that:

• early relationships are one of the primary ways that humans learn to regulate distress
  
• early trauma frequently includes pathology in caregiving relationships, including overt role reversal, abuse, and neglect.
  

Empathic treatment of dissociation, therefore, is based on appreciating the difficulties that arose from an individual’s experience of being alone with overwhelming distress. The relation of dissociation to attachment theory has specific therapeutic implications, including a focus on constructing a safe therapeutic relationship for patients.

Finally, remember that transient dissociative symptoms can be considered normal in high-stress situations. Intensive military training has been found to be associated with a very high incidence (96%) of dissociative symptoms in army recruits.¹⁷

Identifying ‘hidden’ phenomena

Dissociative disorders have been called “diseases of hiddenness”¹⁸ because:

• Many of their clinical characteristics— sense of identity, memory, connectedness, somatosensory phenomena—are alterations in subjective phenomena that lack clearly observable symptoms.
  
• Patients are often reluctant to seek help or divulge their symptoms to clinicians.
  
• When dissociative symptoms are obvious—such as multiple personalities or sudden loss of memories—they may be dismissed or evoke skepticism because of their dramatic presentation.
  

Screening tools. To identify at-risk patients, consider screening with a validated questionnaire such as the Childhood Trauma Questionnaire (CTQ),¹⁹ particularly for patients with psychiatric comorbidity (Table 2). Using the CTQ—which assesses physical, emotional, and sexual abuse and neglect—is a high-yield procedure, given the role of early trauma in brain development and future mental health.²⁰

For more targeted screening, the self-report Dissociative Experiences Scale (DES)²¹ is useful for clinical assessment in conjunction with the clinician-administered diagnostic Structured Clinical Interview for DSM-IV Dissociative Disorder (SCID-D).²²

Table 2

With these findings, consider screening for dissociation

 

Posttraumatic stress disorder
Certain personality disorders (especially borderline personality disorder)
Somatoform disorders (conversion disorders and nonepileptic seizures)
Eating disorders
Substance use disorders
Extensive history of trauma or neglect
Self-harm behavior

Differential diagnosis. Diagnosing dissociative disorders includes ruling out psychopathologies that can present with “look-alike” symptoms (Table 3).

As in Mr. D’s case, dissociative phenomena may attenuate the benefit of post-trauma therapeutic interventions, especially those involving exposure. Therefore:

• assess post-trauma patients for dissociation before you start treatment
  
• make specific alterations in psychotherapy for such patients, as described below.
  

Educating trauma patients that detachment is a normal response to threat¹⁷ can reduce shame about not fighting back.

Table 3

Differential diagnosis: Dissociation ‘look-alikes’

Dissociation symptom	Can be confused with:
Visual or auditory hallucinations, other ‘first-rank’ psychotic symptoms in dissociative identity disorder	Psychotic disorder
‘Blanking out’ (cognitive disruption)	ADHD, seizures
Somatoform (conversion) symptoms	A variety of nonpsychiatric medical problems, including pelvic or abdominal pathology and headaches
Dissociative memory lapses	Learning disability, not paying attention
‘Switching’ between states	Bipolar disorder, rapid cycling
Lack of emotional reaction to traumatic stimuli(numbing response)	Healthy coping
ADHD: attention-deficit/hyperactivity disorder

Medical causes. Because complex partial seizures can cause dissociative symptoms,²³ consider evaluating patients for seizures, head trauma, and structural lesions. Psychogenic nonepileptic seizures (PNES) often occur in conjunction with early trauma, dissociative symptoms, and PTSD.³

Recreational drugs such as ketamine, methylenedioxymethamphetamine (“Ecstasy”), hallucinogens, marijuana, and dextromethorphan also can induce dissociative states. Consider evaluating for use of these substances, some of which may not be detected on a routine drug screen.²⁴

CASE CONTINUED: A tactical shift

Internal distress—such as when remembering painful events—clearly is linked with the appearance of Mr. D’s symptoms. The therapist—recognizing unacknowledged dissociative phenomena—changes Mr. D’s therapeutic strategy from exposure therapy to affect and anxiety regulation, with an explicit focus on attachment security (safety).

The therapist explains to Mr. D that dissociation symptoms are a response to distress, and he can learn more adaptive distress regulation in therapy. The in-session focus shifts to include more direct attention to components of the therapy relationship, including overt disclosure of the therapist’s positive regard and commitment to help the patient and frequent pauses to “check in” that the patient feels present, safe, and understood. With this new focus, Mr. D’s dissociative symptoms resolve and he feels more ready to face and overcome his fear and avoided memories.

Psychotherapy: Putting pieces together

Psychotherapy is the primary treatment, based on understanding dissociative disorders as manifestations of distress-related, traumatic fragmentation of the sense of self, interpersonal relatedness, and capacity for adaptive affect regulation (Table 4).

Depersonalization disorder. Cognitive-behavioral integration has been proposed, based on the idea that detachment from one’s self creates anxiety and reinforces efforts to avoid this internal state and events that trigger it. In an open study of 21 patients with depersonalization disorder, individual cognitive-behavioral therapy (CBT) reduced avoidance, safety behaviors, and symptom monitoring. Measures of dissociation, depression, anxiety, and general functioning also improved.²⁵

Table 4

Tips for conceptualizing dissociative disorders

Ground your understanding of this class of disorders as distress-related breakdowns in functional connection and integration among components of normal consciousness
Consider the overlap among dissociation, certain somatoform disorders (conversion symptoms, pseudoseizures), and PTSD
Maintain a high index of suspicion for dissociative symptoms in patients with early trauma or neglect (consider screening for this); do further evaluation with dissociative-specific tools
Avoid the tendency to assume that reversible, unfamiliar, or peculiar symptoms imply volition or lack of an organic basis
PTSD: posttraumatic stress disorder

Dissociative identity disorder (DID)—the quintessential dissociative disorder—is usually treated by specialists. Treatment is complex, but some components are appropriate for less severe forms of dissociation, including dissociation as part of PTSD.²⁶

Safety, stabilization, and symptom reduction. Providing a safe therapeutic relationship is a primary and necessary part of DID treatment. On that platform, a first step in reintegrating distressing material into the self involves building the patient’s capacity for conscious, flexible affect regulation. This keeps anxiety and distress within a therapeutic “window.”

Graded exposure. Exposure to feared mental contents—typically traumatic memories—is central to trauma-focused therapy. Dissociation is conceptualized as driven by distress greater than the system can bear, loss of adaptive integration, and subsequent fear-based, reflexive avoidance.²⁷ Re-experiencing trauma-related memories in a safe relationship with a new regulatory capacity may work by anchoring patients in an autobiographical memory base.²⁸

Integration of identity and person. Treatment ends when formerly unintegrated or dissociated experiences or parts of the self are integrated into a coherent whole, and the patient can deal adaptively with inter-personal relationships and distress without fragmentation.

 

Adjunctive medications

Few studies have addressed using psychopharmacologic interventions in the heterogeneous dissociative disorders. GABA_A antagonism and 5-HT2a/2c agonism have induced psychotic and dissociative-like symptoms in healthy men,²⁹ and alterations in enzymes such as catechol-O-methyltransferase (COMT) may explain individual vulnerability to trauma.³⁰ Reports of dissociation related to ketamine³¹ and marijuana³² implicate other neurotransmitter systems in their etiology.

DID. Similar to guidelines for borderline personality disorder,³³ guidelines for DID suggest using medications to treat the most prominent symptom clusters such as insomnia, affective instability, and posttraumatic intrusions.

Depersonalization disorder. Trials of fluoxetine and lamotrigine showed no benefit in depersonalization disorder.^34,35 In an open trial of 14 patients, naloxone (mean 120 mg/d) reduced depersonalization symptoms by 30%, as measured by 3 validated scales.³⁶

PTSD-related dissociation. If dissociative symptoms are associated with PTSD, selective serotonin reuptake inhibitors are considered first-line pharmacologic treatment.³⁷ In a 10-week trial of 70 mostly minority adult outpatients with PTSD, paroxetine, ≤60 mg/d, was more effective than placebo in reducing dissociative symptoms, as shown by changes in DES scores.³⁸

Related Resources

• International Society for the Study of Trauma and Dissociation. Site for professionals. www.isst-d.org
  
• National Alliance on Mental Illness (NAMI). Patient education on dissociative disorders. www.nami.org/Content/ContentGroups/Helpline1/Dissociative_Disorders.htm
  

Drug Brand Names

• Fluoxetine • Prozac
  
• Lamotrigine • Lamictal
  
• Naloxone • Narcan
  
• Paroxetine • Paxil
  

Disclosure

Dr. MacDonald is a speaker for Eli Lilly and Company, Janssen, L.P., and Pfizer Inc.

Mr. D, age 45, presents to his primary care physician with panic attacks, nausea, shortness of breath, nightmares, and dizziness 6 months after being assaulted and robbed at an ATM. Following a routine medical workup, the physician diagnoses posttraumatic stress disorder (PTSD) and refers Mr. D for exposure and response prevention therapy.

During graded exposure sessions, Mr. D’s eyes sometimes glaze over and he seems to “float away” from the discussion. When the therapist asks about these symptoms, Mr. D reports having had them as long as he can remember. In school, he says, teachers thought he was a slow learner, a daydreamer, or had attention-deficit/hyperactivity disorder. From what he can recall of his childhood, he describes a history of trauma and neglect with a violent, drug-abusing father and absent mother.

Patients with a history of early abuse or neglect are at risk for dissociative phenomena and other trauma-related psychiatric disorders.¹ The heterogeneous dissociative disorders are often hidden and unrecognized² —as in Mr. D’s case—or present with unfamiliar or atypical symptoms. Understanding and identifying dissociative symptoms is important because:

• Dissociative symptoms worsen prognosis, whether patients have conversion disorders¹ or psychogenic seizures³ or are in psychotherapy.⁴
  
• Dissociative states may impair memory encoding⁵ and decrease patients’ ability to remember therapeutic information.
  
• Symptoms (such as hearing voices in multiple personality disorder) can be confused with those of disorders with different treatment strategies (such as psychotic disorders).⁶
  
• Peritraumatic dissociation may be a risk factor for PTSD.⁷
  

This article presents a practical model for understanding dissociation, reviews clinical characteristics of this family of symptoms, and offers suggestions for assessing and treating patients with dissociative disorders.

Coming together, falling apart

Since Pierre Janet’s first reports on dissociative disorders, a number of theories and models of dissociation have been proposed,⁸ including empirically based, taxonomic models that address DSM-IV-TR categories (Table 1). The model I propose—which attaches a visual metaphor to dissociative phenomena—answers the question, “What is ‘dissociated’ in dissociation disorders?”

Table 1

DSM-IV-TR classification of dissociative disorders

Disorder	Symptoms
Dissociative amnesia	A reversible loss of memory, typically preceded by a stressor
Dissociative fugue	Loss of memory and identity, along with travel away from home
Dissociative identity disorder (formerly multiple personality disorder)	Presence of different identity states, often with lack of connection between them; current models highlight the presence of recurrent dissociative intrusions into many aspects of executive function and self
Depersonalization disorder	Detachment from oneself as a present, feeling person (depersonalization) and the world (derealization)
Dissociative identity disorder NOS	Functionally disturbing dissociative symptoms that do not fit into any of the above
NOS: not otherwise specified
Source: Diagnostic and statistical manual of mental disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

5 components of consciousness. Just as separable wavelengths compose a beam of white light, dissociable “colors” or components of subjective experience constitute a normal state of consciousness. Five implicit components of normal consciousness—present in various degrees, at different times—are seamlessly integrated and associated in real time.

One paired component is a detached “observer” and a more embodied, feeling “experiencer.” The observer is a perspective that begets metacognition (thinking about one’s inner world) and self-observation; it resides in the same body as soma-based “feelings” that unconsciously contribute to the sense of “being present” with oneself and the world in the moment.⁹

A second component is voluntary access to one’s autobiographical memories (memories about the self in time), which are constantly “updated” and integrated with current experiences. This component allows one to distinguish between remembered (past) experiences and “firsthand” (present) experience.

Three other components of normal consciousness are:

• a sense of agency and voluntary control over one’s mental contents, mental activity, and bodily movements
  
• an ongoing connection with one’s body and mind and an understanding of where sensations and images come from
  
• a sense of sequential experience, with relatively smooth transitions (from self at work to self at home, self a week ago to self today, etc) that have a singular referent (an identity).
  

Pathologic dissociation occurs when a prism of distress disperses one of these component “wavelengths” from the main “beam” of consciousness. For example:

• separation of the “observer” and “experiencer” occurs in depersonalization disorder
  
• reversible loss of ability to access memories characterizes dissociative amnesia
  
• disconnection between sequential experiences is a part of dissociative identity disorder.
  

This modular perspective of dissociative disorders parallels a neurophysiologic perspective of mental states as arising from the synchronized integration of the activity of separate, functionally specialized brain regions.

 

¹⁰ Functional neuroimaging of dissociation supports an understanding of these symptoms as “disconnection syndromes” (Box).

Box

Causes of dissociative disorders

As with many psychiatric disorders, the etiology of dissociative phenomena is thought to include the individual patient’s temperamental or constitutional predispositions¹¹ as well as a strong contribution of environmental trauma (early abuse, neglect).¹²

Constitutional predisposition for developing a dissociative disorder may include personality traits such as being easily hypnotized, mental absorption, suggestibility, and a tendency to fantasize.¹³ These characteristics fueled concerns in the 1990s that therapists may contribute to dissociative identity disorder by “digging” for repressed memories in susceptible patients and creating “pseudomemories” of events that did not happen.¹⁴

The issue of repressed traumatic memory and its role in therapy is extremely controversial and contributes to the complexity of psychotherapeutic treatment of dissociation.¹⁵

Early trauma. Factors that make it difficult to define the specific role of early trauma in dissociative disorders include:

• shame and secrecy of early sexual or physical abuse and potential for victims to repress traumatic memories
  
• lability of memory, potential for suggestibility, and difficulty with verification.¹⁴
  

Some experts—influenced by attachment theory—view dissociative phenomena as manifestations of an innate, reflexive relational pattern called disorganized attachment.¹⁶ Attachment theory notes that:

• early relationships are one of the primary ways that humans learn to regulate distress
  
• early trauma frequently includes pathology in caregiving relationships, including overt role reversal, abuse, and neglect.
  

Empathic treatment of dissociation, therefore, is based on appreciating the difficulties that arose from an individual’s experience of being alone with overwhelming distress. The relation of dissociation to attachment theory has specific therapeutic implications, including a focus on constructing a safe therapeutic relationship for patients.

Finally, remember that transient dissociative symptoms can be considered normal in high-stress situations. Intensive military training has been found to be associated with a very high incidence (96%) of dissociative symptoms in army recruits.¹⁷

Identifying ‘hidden’ phenomena

Dissociative disorders have been called “diseases of hiddenness”¹⁸ because:

• Many of their clinical characteristics— sense of identity, memory, connectedness, somatosensory phenomena—are alterations in subjective phenomena that lack clearly observable symptoms.
  
• Patients are often reluctant to seek help or divulge their symptoms to clinicians.
  
• When dissociative symptoms are obvious—such as multiple personalities or sudden loss of memories—they may be dismissed or evoke skepticism because of their dramatic presentation.
  

Screening tools. To identify at-risk patients, consider screening with a validated questionnaire such as the Childhood Trauma Questionnaire (CTQ),¹⁹ particularly for patients with psychiatric comorbidity (Table 2). Using the CTQ—which assesses physical, emotional, and sexual abuse and neglect—is a high-yield procedure, given the role of early trauma in brain development and future mental health.²⁰

For more targeted screening, the self-report Dissociative Experiences Scale (DES)²¹ is useful for clinical assessment in conjunction with the clinician-administered diagnostic Structured Clinical Interview for DSM-IV Dissociative Disorder (SCID-D).²²

Table 2

With these findings, consider screening for dissociation

 

Posttraumatic stress disorder
Certain personality disorders (especially borderline personality disorder)
Somatoform disorders (conversion disorders and nonepileptic seizures)
Eating disorders
Substance use disorders
Extensive history of trauma or neglect
Self-harm behavior

Differential diagnosis. Diagnosing dissociative disorders includes ruling out psychopathologies that can present with “look-alike” symptoms (Table 3).

As in Mr. D’s case, dissociative phenomena may attenuate the benefit of post-trauma therapeutic interventions, especially those involving exposure. Therefore:

• assess post-trauma patients for dissociation before you start treatment
  
• make specific alterations in psychotherapy for such patients, as described below.
  

Educating trauma patients that detachment is a normal response to threat¹⁷ can reduce shame about not fighting back.

Table 3

Differential diagnosis: Dissociation ‘look-alikes’

Dissociation symptom	Can be confused with:
Visual or auditory hallucinations, other ‘first-rank’ psychotic symptoms in dissociative identity disorder	Psychotic disorder
‘Blanking out’ (cognitive disruption)	ADHD, seizures
Somatoform (conversion) symptoms	A variety of nonpsychiatric medical problems, including pelvic or abdominal pathology and headaches
Dissociative memory lapses	Learning disability, not paying attention
‘Switching’ between states	Bipolar disorder, rapid cycling
Lack of emotional reaction to traumatic stimuli(numbing response)	Healthy coping
ADHD: attention-deficit/hyperactivity disorder

Medical causes. Because complex partial seizures can cause dissociative symptoms,²³ consider evaluating patients for seizures, head trauma, and structural lesions. Psychogenic nonepileptic seizures (PNES) often occur in conjunction with early trauma, dissociative symptoms, and PTSD.³

Recreational drugs such as ketamine, methylenedioxymethamphetamine (“Ecstasy”), hallucinogens, marijuana, and dextromethorphan also can induce dissociative states. Consider evaluating for use of these substances, some of which may not be detected on a routine drug screen.²⁴

CASE CONTINUED: A tactical shift

Internal distress—such as when remembering painful events—clearly is linked with the appearance of Mr. D’s symptoms. The therapist—recognizing unacknowledged dissociative phenomena—changes Mr. D’s therapeutic strategy from exposure therapy to affect and anxiety regulation, with an explicit focus on attachment security (safety).

The therapist explains to Mr. D that dissociation symptoms are a response to distress, and he can learn more adaptive distress regulation in therapy. The in-session focus shifts to include more direct attention to components of the therapy relationship, including overt disclosure of the therapist’s positive regard and commitment to help the patient and frequent pauses to “check in” that the patient feels present, safe, and understood. With this new focus, Mr. D’s dissociative symptoms resolve and he feels more ready to face and overcome his fear and avoided memories.

Psychotherapy: Putting pieces together

Psychotherapy is the primary treatment, based on understanding dissociative disorders as manifestations of distress-related, traumatic fragmentation of the sense of self, interpersonal relatedness, and capacity for adaptive affect regulation (Table 4).

Depersonalization disorder. Cognitive-behavioral integration has been proposed, based on the idea that detachment from one’s self creates anxiety and reinforces efforts to avoid this internal state and events that trigger it. In an open study of 21 patients with depersonalization disorder, individual cognitive-behavioral therapy (CBT) reduced avoidance, safety behaviors, and symptom monitoring. Measures of dissociation, depression, anxiety, and general functioning also improved.²⁵

Table 4

Tips for conceptualizing dissociative disorders

Ground your understanding of this class of disorders as distress-related breakdowns in functional connection and integration among components of normal consciousness
Consider the overlap among dissociation, certain somatoform disorders (conversion symptoms, pseudoseizures), and PTSD
Maintain a high index of suspicion for dissociative symptoms in patients with early trauma or neglect (consider screening for this); do further evaluation with dissociative-specific tools
Avoid the tendency to assume that reversible, unfamiliar, or peculiar symptoms imply volition or lack of an organic basis
PTSD: posttraumatic stress disorder

Dissociative identity disorder (DID)—the quintessential dissociative disorder—is usually treated by specialists. Treatment is complex, but some components are appropriate for less severe forms of dissociation, including dissociation as part of PTSD.²⁶

Safety, stabilization, and symptom reduction. Providing a safe therapeutic relationship is a primary and necessary part of DID treatment. On that platform, a first step in reintegrating distressing material into the self involves building the patient’s capacity for conscious, flexible affect regulation. This keeps anxiety and distress within a therapeutic “window.”

Graded exposure. Exposure to feared mental contents—typically traumatic memories—is central to trauma-focused therapy. Dissociation is conceptualized as driven by distress greater than the system can bear, loss of adaptive integration, and subsequent fear-based, reflexive avoidance.²⁷ Re-experiencing trauma-related memories in a safe relationship with a new regulatory capacity may work by anchoring patients in an autobiographical memory base.²⁸

Integration of identity and person. Treatment ends when formerly unintegrated or dissociated experiences or parts of the self are integrated into a coherent whole, and the patient can deal adaptively with inter-personal relationships and distress without fragmentation.

 

Adjunctive medications

Few studies have addressed using psychopharmacologic interventions in the heterogeneous dissociative disorders. GABA_A antagonism and 5-HT2a/2c agonism have induced psychotic and dissociative-like symptoms in healthy men,²⁹ and alterations in enzymes such as catechol-O-methyltransferase (COMT) may explain individual vulnerability to trauma.³⁰ Reports of dissociation related to ketamine³¹ and marijuana³² implicate other neurotransmitter systems in their etiology.

DID. Similar to guidelines for borderline personality disorder,³³ guidelines for DID suggest using medications to treat the most prominent symptom clusters such as insomnia, affective instability, and posttraumatic intrusions.

Depersonalization disorder. Trials of fluoxetine and lamotrigine showed no benefit in depersonalization disorder.^34,35 In an open trial of 14 patients, naloxone (mean 120 mg/d) reduced depersonalization symptoms by 30%, as measured by 3 validated scales.³⁶

PTSD-related dissociation. If dissociative symptoms are associated with PTSD, selective serotonin reuptake inhibitors are considered first-line pharmacologic treatment.³⁷ In a 10-week trial of 70 mostly minority adult outpatients with PTSD, paroxetine, ≤60 mg/d, was more effective than placebo in reducing dissociative symptoms, as shown by changes in DES scores.³⁸

Related Resources

• International Society for the Study of Trauma and Dissociation. Site for professionals. www.isst-d.org
  
• National Alliance on Mental Illness (NAMI). Patient education on dissociative disorders. www.nami.org/Content/ContentGroups/Helpline1/Dissociative_Disorders.htm
  

Drug Brand Names

• Fluoxetine • Prozac
  
• Lamotrigine • Lamictal
  
• Naloxone • Narcan
  
• Paroxetine • Paxil
  

Disclosure

Dr. MacDonald is a speaker for Eli Lilly and Company, Janssen, L.P., and Pfizer Inc.

Mr. D, age 45, presents to his primary care physician with panic attacks, nausea, shortness of breath, nightmares, and dizziness 6 months after being assaulted and robbed at an ATM. Following a routine medical workup, the physician diagnoses posttraumatic stress disorder (PTSD) and refers Mr. D for exposure and response prevention therapy.

During graded exposure sessions, Mr. D’s eyes sometimes glaze over and he seems to “float away” from the discussion. When the therapist asks about these symptoms, Mr. D reports having had them as long as he can remember. In school, he says, teachers thought he was a slow learner, a daydreamer, or had attention-deficit/hyperactivity disorder. From what he can recall of his childhood, he describes a history of trauma and neglect with a violent, drug-abusing father and absent mother.

Patients with a history of early abuse or neglect are at risk for dissociative phenomena and other trauma-related psychiatric disorders.¹ The heterogeneous dissociative disorders are often hidden and unrecognized² —as in Mr. D’s case—or present with unfamiliar or atypical symptoms. Understanding and identifying dissociative symptoms is important because:

• Dissociative symptoms worsen prognosis, whether patients have conversion disorders¹ or psychogenic seizures³ or are in psychotherapy.⁴
  
• Dissociative states may impair memory encoding⁵ and decrease patients’ ability to remember therapeutic information.
  
• Symptoms (such as hearing voices in multiple personality disorder) can be confused with those of disorders with different treatment strategies (such as psychotic disorders).⁶
  
• Peritraumatic dissociation may be a risk factor for PTSD.⁷
  

This article presents a practical model for understanding dissociation, reviews clinical characteristics of this family of symptoms, and offers suggestions for assessing and treating patients with dissociative disorders.

Coming together, falling apart

Since Pierre Janet’s first reports on dissociative disorders, a number of theories and models of dissociation have been proposed,⁸ including empirically based, taxonomic models that address DSM-IV-TR categories (Table 1). The model I propose—which attaches a visual metaphor to dissociative phenomena—answers the question, “What is ‘dissociated’ in dissociation disorders?”

Table 1

DSM-IV-TR classification of dissociative disorders

Disorder	Symptoms
Dissociative amnesia	A reversible loss of memory, typically preceded by a stressor
Dissociative fugue	Loss of memory and identity, along with travel away from home
Dissociative identity disorder (formerly multiple personality disorder)	Presence of different identity states, often with lack of connection between them; current models highlight the presence of recurrent dissociative intrusions into many aspects of executive function and self
Depersonalization disorder	Detachment from oneself as a present, feeling person (depersonalization) and the world (derealization)
Dissociative identity disorder NOS	Functionally disturbing dissociative symptoms that do not fit into any of the above
NOS: not otherwise specified
Source: Diagnostic and statistical manual of mental disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

5 components of consciousness. Just as separable wavelengths compose a beam of white light, dissociable “colors” or components of subjective experience constitute a normal state of consciousness. Five implicit components of normal consciousness—present in various degrees, at different times—are seamlessly integrated and associated in real time.

One paired component is a detached “observer” and a more embodied, feeling “experiencer.” The observer is a perspective that begets metacognition (thinking about one’s inner world) and self-observation; it resides in the same body as soma-based “feelings” that unconsciously contribute to the sense of “being present” with oneself and the world in the moment.⁹

A second component is voluntary access to one’s autobiographical memories (memories about the self in time), which are constantly “updated” and integrated with current experiences. This component allows one to distinguish between remembered (past) experiences and “firsthand” (present) experience.

Three other components of normal consciousness are:

• a sense of agency and voluntary control over one’s mental contents, mental activity, and bodily movements
  
• an ongoing connection with one’s body and mind and an understanding of where sensations and images come from
  
• a sense of sequential experience, with relatively smooth transitions (from self at work to self at home, self a week ago to self today, etc) that have a singular referent (an identity).
  

Pathologic dissociation occurs when a prism of distress disperses one of these component “wavelengths” from the main “beam” of consciousness. For example:

• separation of the “observer” and “experiencer” occurs in depersonalization disorder
  
• reversible loss of ability to access memories characterizes dissociative amnesia
  
• disconnection between sequential experiences is a part of dissociative identity disorder.
  

This modular perspective of dissociative disorders parallels a neurophysiologic perspective of mental states as arising from the synchronized integration of the activity of separate, functionally specialized brain regions.

 

¹⁰ Functional neuroimaging of dissociation supports an understanding of these symptoms as “disconnection syndromes” (Box).

Box

Causes of dissociative disorders

As with many psychiatric disorders, the etiology of dissociative phenomena is thought to include the individual patient’s temperamental or constitutional predispositions¹¹ as well as a strong contribution of environmental trauma (early abuse, neglect).¹²

Constitutional predisposition for developing a dissociative disorder may include personality traits such as being easily hypnotized, mental absorption, suggestibility, and a tendency to fantasize.¹³ These characteristics fueled concerns in the 1990s that therapists may contribute to dissociative identity disorder by “digging” for repressed memories in susceptible patients and creating “pseudomemories” of events that did not happen.¹⁴

The issue of repressed traumatic memory and its role in therapy is extremely controversial and contributes to the complexity of psychotherapeutic treatment of dissociation.¹⁵

Early trauma. Factors that make it difficult to define the specific role of early trauma in dissociative disorders include:

• shame and secrecy of early sexual or physical abuse and potential for victims to repress traumatic memories
  
• lability of memory, potential for suggestibility, and difficulty with verification.¹⁴
  

Some experts—influenced by attachment theory—view dissociative phenomena as manifestations of an innate, reflexive relational pattern called disorganized attachment.¹⁶ Attachment theory notes that:

• early relationships are one of the primary ways that humans learn to regulate distress
  
• early trauma frequently includes pathology in caregiving relationships, including overt role reversal, abuse, and neglect.
  

Empathic treatment of dissociation, therefore, is based on appreciating the difficulties that arose from an individual’s experience of being alone with overwhelming distress. The relation of dissociation to attachment theory has specific therapeutic implications, including a focus on constructing a safe therapeutic relationship for patients.

Finally, remember that transient dissociative symptoms can be considered normal in high-stress situations. Intensive military training has been found to be associated with a very high incidence (96%) of dissociative symptoms in army recruits.¹⁷

Identifying ‘hidden’ phenomena

Dissociative disorders have been called “diseases of hiddenness”¹⁸ because:

• Many of their clinical characteristics— sense of identity, memory, connectedness, somatosensory phenomena—are alterations in subjective phenomena that lack clearly observable symptoms.
  
• Patients are often reluctant to seek help or divulge their symptoms to clinicians.
  
• When dissociative symptoms are obvious—such as multiple personalities or sudden loss of memories—they may be dismissed or evoke skepticism because of their dramatic presentation.
  

Screening tools. To identify at-risk patients, consider screening with a validated questionnaire such as the Childhood Trauma Questionnaire (CTQ),¹⁹ particularly for patients with psychiatric comorbidity (Table 2). Using the CTQ—which assesses physical, emotional, and sexual abuse and neglect—is a high-yield procedure, given the role of early trauma in brain development and future mental health.²⁰

For more targeted screening, the self-report Dissociative Experiences Scale (DES)²¹ is useful for clinical assessment in conjunction with the clinician-administered diagnostic Structured Clinical Interview for DSM-IV Dissociative Disorder (SCID-D).²²

Table 2

With these findings, consider screening for dissociation

 

Posttraumatic stress disorder
Certain personality disorders (especially borderline personality disorder)
Somatoform disorders (conversion disorders and nonepileptic seizures)
Eating disorders
Substance use disorders
Extensive history of trauma or neglect
Self-harm behavior

Differential diagnosis. Diagnosing dissociative disorders includes ruling out psychopathologies that can present with “look-alike” symptoms (Table 3).

As in Mr. D’s case, dissociative phenomena may attenuate the benefit of post-trauma therapeutic interventions, especially those involving exposure. Therefore:

• assess post-trauma patients for dissociation before you start treatment
  
• make specific alterations in psychotherapy for such patients, as described below.
  

Educating trauma patients that detachment is a normal response to threat¹⁷ can reduce shame about not fighting back.

Table 3

Differential diagnosis: Dissociation ‘look-alikes’

Dissociation symptom	Can be confused with:
Visual or auditory hallucinations, other ‘first-rank’ psychotic symptoms in dissociative identity disorder	Psychotic disorder
‘Blanking out’ (cognitive disruption)	ADHD, seizures
Somatoform (conversion) symptoms	A variety of nonpsychiatric medical problems, including pelvic or abdominal pathology and headaches
Dissociative memory lapses	Learning disability, not paying attention
‘Switching’ between states	Bipolar disorder, rapid cycling
Lack of emotional reaction to traumatic stimuli(numbing response)	Healthy coping
ADHD: attention-deficit/hyperactivity disorder

Medical causes. Because complex partial seizures can cause dissociative symptoms,²³ consider evaluating patients for seizures, head trauma, and structural lesions. Psychogenic nonepileptic seizures (PNES) often occur in conjunction with early trauma, dissociative symptoms, and PTSD.³

Recreational drugs such as ketamine, methylenedioxymethamphetamine (“Ecstasy”), hallucinogens, marijuana, and dextromethorphan also can induce dissociative states. Consider evaluating for use of these substances, some of which may not be detected on a routine drug screen.²⁴

CASE CONTINUED: A tactical shift

Internal distress—such as when remembering painful events—clearly is linked with the appearance of Mr. D’s symptoms. The therapist—recognizing unacknowledged dissociative phenomena—changes Mr. D’s therapeutic strategy from exposure therapy to affect and anxiety regulation, with an explicit focus on attachment security (safety).

The therapist explains to Mr. D that dissociation symptoms are a response to distress, and he can learn more adaptive distress regulation in therapy. The in-session focus shifts to include more direct attention to components of the therapy relationship, including overt disclosure of the therapist’s positive regard and commitment to help the patient and frequent pauses to “check in” that the patient feels present, safe, and understood. With this new focus, Mr. D’s dissociative symptoms resolve and he feels more ready to face and overcome his fear and avoided memories.

Psychotherapy: Putting pieces together

Psychotherapy is the primary treatment, based on understanding dissociative disorders as manifestations of distress-related, traumatic fragmentation of the sense of self, interpersonal relatedness, and capacity for adaptive affect regulation (Table 4).

Depersonalization disorder. Cognitive-behavioral integration has been proposed, based on the idea that detachment from one’s self creates anxiety and reinforces efforts to avoid this internal state and events that trigger it. In an open study of 21 patients with depersonalization disorder, individual cognitive-behavioral therapy (CBT) reduced avoidance, safety behaviors, and symptom monitoring. Measures of dissociation, depression, anxiety, and general functioning also improved.²⁵

Table 4

Tips for conceptualizing dissociative disorders

Ground your understanding of this class of disorders as distress-related breakdowns in functional connection and integration among components of normal consciousness
Consider the overlap among dissociation, certain somatoform disorders (conversion symptoms, pseudoseizures), and PTSD
Maintain a high index of suspicion for dissociative symptoms in patients with early trauma or neglect (consider screening for this); do further evaluation with dissociative-specific tools
Avoid the tendency to assume that reversible, unfamiliar, or peculiar symptoms imply volition or lack of an organic basis
PTSD: posttraumatic stress disorder

Dissociative identity disorder (DID)—the quintessential dissociative disorder—is usually treated by specialists. Treatment is complex, but some components are appropriate for less severe forms of dissociation, including dissociation as part of PTSD.²⁶

Safety, stabilization, and symptom reduction. Providing a safe therapeutic relationship is a primary and necessary part of DID treatment. On that platform, a first step in reintegrating distressing material into the self involves building the patient’s capacity for conscious, flexible affect regulation. This keeps anxiety and distress within a therapeutic “window.”

Graded exposure. Exposure to feared mental contents—typically traumatic memories—is central to trauma-focused therapy. Dissociation is conceptualized as driven by distress greater than the system can bear, loss of adaptive integration, and subsequent fear-based, reflexive avoidance.²⁷ Re-experiencing trauma-related memories in a safe relationship with a new regulatory capacity may work by anchoring patients in an autobiographical memory base.²⁸

Integration of identity and person. Treatment ends when formerly unintegrated or dissociated experiences or parts of the self are integrated into a coherent whole, and the patient can deal adaptively with inter-personal relationships and distress without fragmentation.

 

Adjunctive medications

Few studies have addressed using psychopharmacologic interventions in the heterogeneous dissociative disorders. GABA_A antagonism and 5-HT2a/2c agonism have induced psychotic and dissociative-like symptoms in healthy men,²⁹ and alterations in enzymes such as catechol-O-methyltransferase (COMT) may explain individual vulnerability to trauma.³⁰ Reports of dissociation related to ketamine³¹ and marijuana³² implicate other neurotransmitter systems in their etiology.

DID. Similar to guidelines for borderline personality disorder,³³ guidelines for DID suggest using medications to treat the most prominent symptom clusters such as insomnia, affective instability, and posttraumatic intrusions.

Depersonalization disorder. Trials of fluoxetine and lamotrigine showed no benefit in depersonalization disorder.^34,35 In an open trial of 14 patients, naloxone (mean 120 mg/d) reduced depersonalization symptoms by 30%, as measured by 3 validated scales.³⁶

PTSD-related dissociation. If dissociative symptoms are associated with PTSD, selective serotonin reuptake inhibitors are considered first-line pharmacologic treatment.³⁷ In a 10-week trial of 70 mostly minority adult outpatients with PTSD, paroxetine, ≤60 mg/d, was more effective than placebo in reducing dissociative symptoms, as shown by changes in DES scores.³⁸

Related Resources

• International Society for the Study of Trauma and Dissociation. Site for professionals. www.isst-d.org
  
• National Alliance on Mental Illness (NAMI). Patient education on dissociative disorders. www.nami.org/Content/ContentGroups/Helpline1/Dissociative_Disorders.htm
  

Drug Brand Names

• Fluoxetine • Prozac
  
• Lamotrigine • Lamictal
  
• Naloxone • Narcan
  
• Paroxetine • Paxil
  

Disclosure

Dr. MacDonald is a speaker for Eli Lilly and Company, Janssen, L.P., and Pfizer Inc.

Mr. W, age 50, presents to the psychiatry clinic with obsessive-compulsive disorder (OCD) symptoms. At his first interview, he says he spends every waking hour obsessing over whether or not he does things “right.” These thoughts force him to compulsively check and recheck everything he does, from simple body movements to complex computer tasks.

He has a history of OCD since age 8, with intermittent episodes of major depression. He reports that several years ago, he had a “miraculous” response to clomipramine for several weeks but has not responded to any other medication. Nevertheless, he continues taking clomipramine, 50 mg/d, hoping that it “might eventually do some good.” He adds that when he tried to increase the dose, he suffered from “terrible constipation” despite regular use of a methylcellulose fiber supplement.

The psychiatrist discontinues clomipramine and starts Mr. W on duloxetine, 90 mg/d. At the next visit, Mr. W complains that his constipation is much worse, so the psychiatrist decreases duloxetine to 60 mg/d, which eventually provides some relief. Because Mr. W has minimal response to duloxetine after 6 months, the psychiatrist adds olanzapine. Although this agent is anticholinergic, the patient had responded to a previous trial of this antipsychotic. Soon after, Mr. W experiences severe constipation.

Psychiatric patients face a host of potential causes of constipation, including:

• use of psychotropics and other medications
  
• decreased eating or physical activity as a result of depression or another psychiatric disorder
  
• medical comorbidities that decrease gastrointestinal (GI) motility.
  

Constipation carries a tremendous cost in terms of resources and quality of life.^1-7 This condition also can make patients stop taking medications. You can help patients avoid the discomfort and quality-of-life consequences by promptly diagnosing constipation and following a 5-step treatment algorithm that has shown value in our clinical practice.

Box 1

What to look for

When evaluating a patient who complains of constipation, first determine what he or she means by “constipation.” Do not rely on frequency of bowel movements as the only criterion for diagnosis. Under Rome Committee for Functional Gastrointestinal Disorders guidelines for diagnosis of chronic (or functional) constipation, patients who move their bowels daily may meet criteria for chronic constipation if they experience straining, incomplete evacuation, or other symptoms (Box 1).⁸

Many patients who complain of constipation have daily, regular bowel movements that produce hard, difficult-to-pass stool or require straining or manual maneuvers. Take a careful history including:

• stool frequency and quality
  
• straining
  
• manual maneuvers (disimpaction or manual pelvic floor support)
  
• sensation of blockage or incomplete evacuation.
  

In women, take a history of childbirth and obstetric or gynecologic surgery. Also determine the timing of symptom onset related to any new prescription or over-the-counter medications or supplements.

‘Alarm’ symptoms. For psychiatrists, the most important part of the Rome guidelines are the “alarm” symptoms:

• age ≥50 years
  
• family history of colon cancer or polyps
  
• family history of inflammatory bowel disease (ulcerative colitis or Crohn’s disease)
  
• rectal bleeding, anemia
  
• weight loss >10 pounds
  
• new onset of chronic constipation without apparent cause in an elderly patient
  
• severe, persistent constipation refractory to conservative management.⁹
  

Refer a patient with any of these symptoms to a specialist for endoscopic or clinical evaluation. Follow United States Preventative Services Task Force recommendations for colorectal cancer screening of all patients age ≥50 (Table 1).¹⁰

Table 1

Colorectal cancer screening recommendations*

Test	Frequency
Fecal occult blood testing (FOBT)	Annually
Sigmoidoscopy	Every 5 years
FOBT and sigmoidoscopy	Every 5 years
Double contrast barium enema	Every 5 years
Colonoscopy	Every 10 years
* For patients age=50. For higher-risk patients, it is reasonable to begin screening at a younger age
Source: Reference 10

Determining the cause

Common causes of constipation include altered visceral sensitivity, decreased GI motility, alterations in pelvic and anorectal musculature, and alterations in the enteric nervous system. Systemic causes are less common and include electrolyte abnormalities (hypercalcemia and hypokalemia) and endocrine disorders (hypothyroidism and diabetes mellitus).

Some patients’ constipation is caused by involuntarily contracting the pelvic floor muscles or suppressing the urge to defecate (Box 2).^1,11,12 Suspect this in patients who strain repeatedly to pass soft or liquid stool.

Medication side effects are probably the most common constipation cause psychiatrists will encounter. Many psychotropics have anticholinergic effects that decrease GI motility and cause constipation. The most commonly implicated drugs are:

 

• older tricyclic antidepressants (such as amitriptyline)
  
• antipsychotics.
  

Among antipsychotics, clozapine, thioridazine, olanzapine, and chlorpromazine probably have the greatest anticholinergic effects.¹³ Many selective serotonin reuptake inhibitors also can cause constipation.

Box 2

Older psychiatric patients with constipation may be taking medications for medical conditions—particularly alpha, beta, and calcium channel blockers—that may have synergistic effects on slowing bowel motility. For these patients you may not have the luxury of making multiple medication changes. The correct management strategy may be to add docusate sodium, a stool softener available over-the-counter as Colace.

Other psychiatric-related causes. Patients with depression may experience decreased stool output because of a lack of food intake or physical activity. These causes may be effectively addressed by treating the depression.

Give special consideration to patients with eating disorders and those who routinely use laxatives. A patient who is not eating will not produce the same amount of stool as one who eats regularly.

Constipated patients may require escalating doses of laxatives to obtain symptom relief; this does not constitute laxative abuse but rather tachyphylaxis. Chronic laxative use has not been shown to permanently decrease colonic motility,¹⁴ but patients who use laxatives chronically may have altered expectations of what is normal.

CASE CONTINUED: Recurring symptoms

After discontinuing Mr. W’s olanzapine and duloxetine, the psychiatrist prescribes polyethylene glycol solution (MiraLax) and instructs Mr. W to increase his daily fluid and fiber intake. Although the solution works well, Mr. W complains of the cost. He then resumes methyl cellulose and starts taking magnesium hydroxide chewable tablets (Milk of Magnesia) every 2 to 4 days as needed for constipation.

The psychiatrist prescribes mirtazapine for OCD symptoms, but soon stops this regimen because Mr. W complains of worsening constipation. Next Mr. W is started on fluvoxamine, which he had tried briefly many years before. The dosage is gradually titrated to 150 mg/d. Although Mr. W’s OCD improves somewhat, he complains of agitation and once again of worsening constipation.

Treatment algorithm

To minimize trial and error, we use a stepwise approach to treating constipation (Algorithm).^8,11,15 Although many standard recommendations have not been evaluated in large randomized controlled trials, they are supported by decades of observed actions among clinicians and thus remain valuable.

Multiple nonprescription agents are available to treat constipation, including:

• bulking agents (fiber supplements)
  
• lubricating agents
  
• stool softening agents
  
• stimulant and osmotic laxatives (Table 2).⁸
  

Advise patients that they may need to try multiple agents to find one that is tolerable and effective.

Steps 1 & 2. When initial attempts at increasing physical activity, fluid, and dietary fiber fail to yield a response, fiber supplements are commonly used as a second step in managing constipation. We advocate beginning with a supplement that contains psyllium—such as Fiber-all or Metamucil—because psyllium has been shown to increase stool frequency. Supplements that contain methylcellulose (Citrucel), polycarbophil (such as Equalactin and Mitrolan), or bran have either not shown efficacy or have not been studied rigorously enough to merit recommendation.¹⁰ Some patients respond to other fiber products, but start a fibernaïve patient with a psyllium-containing supplement.

Fiber supplements may cause increased gas and bloating, so start at a low dose and gradually increase over several weeks to mitigate these side effects.

Step 3. If fiber supplements fail, try a stimulant or osmotic laxative. Senna compounds such as Ex-Lax and Senokot and bisacodyl products such as Correctol and Dulcolax are stimulant laxatives. For patients who prefer natural therapies, we point out that senna is derived from plants.

 

In our experience, patients usually have tried bisacodyl before seeking treatment for constipation. Although bisacodyl may be effective for some patients, others may need something stronger. Many gastroenterologists prefer prescribing osmotic or prescription laxatives.

Step 4. Osmotic laxatives generally are liquids, including magnesium hydroxide, polyethylene glycol solution, and the prescription agent lactulose. Magnesium hydroxide is inexpensive and can be taken chronically.

Algorithm

A stepwise approach to managing constipation

Step 1
Recommendation	Comments
Increase activity or daily walking	Not rigorously studied in constipated patients; exercise is associated with decreased orocecal transit time15
Increase fluid intake	Not rigorously studied in constipated patients8
Increase dietary fiber intake	Not rigorously studied in constipated patients8
↓
Step 2
Recommendation	Comments
Fiber supplements	Psyllium compounds may be superior to methylcellulose, polycarbophil, and bran11
↓
Step 3
Recommendation	Comments
Over-the-counter laxative pills	Senna compounds are derived from plants
↓
Step 4
Recommendation	Comments
Over-the-counter laxative solutions	Milk of Magnesia is very inexpensive
↓
Step 5
Recommendation	Comments
Prescription laxatives	Lubiprostone causes fetal loss in animals; tegaserod is available only under a treatment investigational new drug protocol

Table 2

Commonly used laxatives: Mechanisms of action

Category	Agents
Bulk-forming	Methylcellulose (Citrucel), polycarbophil (Equalactin, Mitrolan, others), psyllium (Fiberall, Metamucil, others)
Lubricating	Glycerin (Sani-Supp), magnesium hydroxide and mineral oil (Magnolax), mineral oil (Fleet Mineral Oil, Zymenol, others)
Stool softener	Docusate sodium (Colace)
Osmotic	Magnesium hydroxide (Milk of Magnesia), polyethylene glycol (MiraLax), lactulose* (Cholac Syrup, Constulose, others), lubiprostone* (Amitiza)
Stimulant	Bisacodyl (Correctol, Dulcolax, others), castor oil (Alphamul, Emulsoil, others), senna/sennosides (Ex-Lax, Senokot, others), sodium bicarbonate and potassium bitartrate (Ceo-Two evacuant)
* Available by prescription only
Source: Reference 8

Prescription medications

Tegaserod is a partial 5-HT4 agonist and stimulator of GI motility and secretion. It also decreases visceral sensitivity.¹⁶ Tegaserod’s manufacturer voluntarily withdrew the drug from the market because it may increase risk of cardiovascular ischemic events, including angina, heart attack, and stroke. Tegaserod is available only under a treatment investigational new drug (IND) protocol that includes obtaining approval from a local institutional review board. We recommend that psychiatrists should not prescribe tegaserod but refer patients to experienced gastroenterologists or other GI specialists.

Lubiprostone is a selective chloride channel activator that works only in the gut and results in net fluid excretion and increased stool frequency. The molecule is a prostaglandin derivative and is poorly absorbed.¹⁷

Because lubiprostone has been shown to cause fetal loss in animals (at the equivalent of 2 and 6 times the recommended human dose), women of reproductive age should use contraception while taking lubiprostone and carefully consider the risks and benefits of lubiprostone use during pregnancy.

CASE CONTINUED: Finding an effective strategy

The psychiatrist prescribes lubiprostone, 24 mcg bid, but Mr. W once again complains of the expense and says the drug does not work well. He quickly returns to his intermittent use of magnesium hydroxide tablets and occasionally takes bisacodyl tablets.

To address Mr. W’s OCD, the psychiatrist adds risperidone, 0.5 mg bid, to Mr. W’s regimen. He has a modest response in OCD symptoms—30% of his day is now symptom- free— without worsening his constipation.

Probiotics and prebiotics

Emerging therapies for constipation include probiotics and prebiotics, which attempt to alter the gut flora and milieu. The primary bacterial agents are Lactobacillus species and Bifidobacterium species. At least one probiotic Bifidobacterium product—Activia—is being marketed in the United States as a fortified yogurt.

Because limited clinical data are available on the effect of probiotics and prebiotics on constipation, their routine use is not indicated. However, patients who prefer not to take medication may wish to try them. Because these agents are active cells, advise patients to purchase a supplement with “live and active” cultures. Supplements that are shipped, stored, or sold at room temperature likely contain very few (if any) live cultures.

Investigational medications. Renzapride is a 5HT4 receptor agonist and 5HT3 receptor antagonist that has shown promise in a pilot study¹⁸ and is in phase III trials. Linaclotide is a peptide that activates chloride and bicarbonate secretion in the gut and may reduce visceral hypersensitivity. It too has shown promise in a pilot study.¹⁹

Related resources

• Rome Foundation. Functional gastrointestinal disorders. www.romecriteria.org.
  
• Bleser S, Brunton S, Carmichael B, et al. Management of chronic constipation: recommendations from a consensus panel. J Fam Pract 2005;54(8):691-8.
  

Drug brand name

• Amitriptyline • Elavil, Endep
  
• Chlorpromazine • Thorazine
  
• Clomipramine • Anafranil
  
• Clozapine • Clozaril
  
• Duloxetine • Cymbalta
  
• Fluvoxamine • Luvox
  
• Lactulose • Cholac Syrup, Constulose, others
  
• Lubiprostone • Amitiza
  
• Mirtazapine • Remeron
  
• Olanzapine • Zyprexa
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Tegaserod • Zelnorm
  

Disclosure

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

Acknowledgment

This project was partially supported by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality.

Mr. W, age 50, presents to the psychiatry clinic with obsessive-compulsive disorder (OCD) symptoms. At his first interview, he says he spends every waking hour obsessing over whether or not he does things “right.” These thoughts force him to compulsively check and recheck everything he does, from simple body movements to complex computer tasks.

He has a history of OCD since age 8, with intermittent episodes of major depression. He reports that several years ago, he had a “miraculous” response to clomipramine for several weeks but has not responded to any other medication. Nevertheless, he continues taking clomipramine, 50 mg/d, hoping that it “might eventually do some good.” He adds that when he tried to increase the dose, he suffered from “terrible constipation” despite regular use of a methylcellulose fiber supplement.

The psychiatrist discontinues clomipramine and starts Mr. W on duloxetine, 90 mg/d. At the next visit, Mr. W complains that his constipation is much worse, so the psychiatrist decreases duloxetine to 60 mg/d, which eventually provides some relief. Because Mr. W has minimal response to duloxetine after 6 months, the psychiatrist adds olanzapine. Although this agent is anticholinergic, the patient had responded to a previous trial of this antipsychotic. Soon after, Mr. W experiences severe constipation.

Psychiatric patients face a host of potential causes of constipation, including:

• use of psychotropics and other medications
  
• decreased eating or physical activity as a result of depression or another psychiatric disorder
  
• medical comorbidities that decrease gastrointestinal (GI) motility.
  

Constipation carries a tremendous cost in terms of resources and quality of life.^1-7 This condition also can make patients stop taking medications. You can help patients avoid the discomfort and quality-of-life consequences by promptly diagnosing constipation and following a 5-step treatment algorithm that has shown value in our clinical practice.

Box 1

What to look for

When evaluating a patient who complains of constipation, first determine what he or she means by “constipation.” Do not rely on frequency of bowel movements as the only criterion for diagnosis. Under Rome Committee for Functional Gastrointestinal Disorders guidelines for diagnosis of chronic (or functional) constipation, patients who move their bowels daily may meet criteria for chronic constipation if they experience straining, incomplete evacuation, or other symptoms (Box 1).⁸

Many patients who complain of constipation have daily, regular bowel movements that produce hard, difficult-to-pass stool or require straining or manual maneuvers. Take a careful history including:

• stool frequency and quality
  
• straining
  
• manual maneuvers (disimpaction or manual pelvic floor support)
  
• sensation of blockage or incomplete evacuation.
  

In women, take a history of childbirth and obstetric or gynecologic surgery. Also determine the timing of symptom onset related to any new prescription or over-the-counter medications or supplements.

‘Alarm’ symptoms. For psychiatrists, the most important part of the Rome guidelines are the “alarm” symptoms:

• age ≥50 years
  
• family history of colon cancer or polyps
  
• family history of inflammatory bowel disease (ulcerative colitis or Crohn’s disease)
  
• rectal bleeding, anemia
  
• weight loss >10 pounds
  
• new onset of chronic constipation without apparent cause in an elderly patient
  
• severe, persistent constipation refractory to conservative management.⁹
  

Refer a patient with any of these symptoms to a specialist for endoscopic or clinical evaluation. Follow United States Preventative Services Task Force recommendations for colorectal cancer screening of all patients age ≥50 (Table 1).¹⁰

Table 1

Colorectal cancer screening recommendations*

Test	Frequency
Fecal occult blood testing (FOBT)	Annually
Sigmoidoscopy	Every 5 years
FOBT and sigmoidoscopy	Every 5 years
Double contrast barium enema	Every 5 years
Colonoscopy	Every 10 years
* For patients age=50. For higher-risk patients, it is reasonable to begin screening at a younger age
Source: Reference 10

Determining the cause

Common causes of constipation include altered visceral sensitivity, decreased GI motility, alterations in pelvic and anorectal musculature, and alterations in the enteric nervous system. Systemic causes are less common and include electrolyte abnormalities (hypercalcemia and hypokalemia) and endocrine disorders (hypothyroidism and diabetes mellitus).

Some patients’ constipation is caused by involuntarily contracting the pelvic floor muscles or suppressing the urge to defecate (Box 2).^1,11,12 Suspect this in patients who strain repeatedly to pass soft or liquid stool.

Medication side effects are probably the most common constipation cause psychiatrists will encounter. Many psychotropics have anticholinergic effects that decrease GI motility and cause constipation. The most commonly implicated drugs are:

 

• older tricyclic antidepressants (such as amitriptyline)
  
• antipsychotics.
  

Among antipsychotics, clozapine, thioridazine, olanzapine, and chlorpromazine probably have the greatest anticholinergic effects.¹³ Many selective serotonin reuptake inhibitors also can cause constipation.

Box 2

Older psychiatric patients with constipation may be taking medications for medical conditions—particularly alpha, beta, and calcium channel blockers—that may have synergistic effects on slowing bowel motility. For these patients you may not have the luxury of making multiple medication changes. The correct management strategy may be to add docusate sodium, a stool softener available over-the-counter as Colace.

Other psychiatric-related causes. Patients with depression may experience decreased stool output because of a lack of food intake or physical activity. These causes may be effectively addressed by treating the depression.

Give special consideration to patients with eating disorders and those who routinely use laxatives. A patient who is not eating will not produce the same amount of stool as one who eats regularly.

Constipated patients may require escalating doses of laxatives to obtain symptom relief; this does not constitute laxative abuse but rather tachyphylaxis. Chronic laxative use has not been shown to permanently decrease colonic motility,¹⁴ but patients who use laxatives chronically may have altered expectations of what is normal.

CASE CONTINUED: Recurring symptoms

After discontinuing Mr. W’s olanzapine and duloxetine, the psychiatrist prescribes polyethylene glycol solution (MiraLax) and instructs Mr. W to increase his daily fluid and fiber intake. Although the solution works well, Mr. W complains of the cost. He then resumes methyl cellulose and starts taking magnesium hydroxide chewable tablets (Milk of Magnesia) every 2 to 4 days as needed for constipation.

The psychiatrist prescribes mirtazapine for OCD symptoms, but soon stops this regimen because Mr. W complains of worsening constipation. Next Mr. W is started on fluvoxamine, which he had tried briefly many years before. The dosage is gradually titrated to 150 mg/d. Although Mr. W’s OCD improves somewhat, he complains of agitation and once again of worsening constipation.

Treatment algorithm

To minimize trial and error, we use a stepwise approach to treating constipation (Algorithm).^8,11,15 Although many standard recommendations have not been evaluated in large randomized controlled trials, they are supported by decades of observed actions among clinicians and thus remain valuable.

Multiple nonprescription agents are available to treat constipation, including:

• bulking agents (fiber supplements)
  
• lubricating agents
  
• stool softening agents
  
• stimulant and osmotic laxatives (Table 2).⁸
  

Advise patients that they may need to try multiple agents to find one that is tolerable and effective.

Steps 1 & 2. When initial attempts at increasing physical activity, fluid, and dietary fiber fail to yield a response, fiber supplements are commonly used as a second step in managing constipation. We advocate beginning with a supplement that contains psyllium—such as Fiber-all or Metamucil—because psyllium has been shown to increase stool frequency. Supplements that contain methylcellulose (Citrucel), polycarbophil (such as Equalactin and Mitrolan), or bran have either not shown efficacy or have not been studied rigorously enough to merit recommendation.¹⁰ Some patients respond to other fiber products, but start a fibernaïve patient with a psyllium-containing supplement.

Fiber supplements may cause increased gas and bloating, so start at a low dose and gradually increase over several weeks to mitigate these side effects.

Step 3. If fiber supplements fail, try a stimulant or osmotic laxative. Senna compounds such as Ex-Lax and Senokot and bisacodyl products such as Correctol and Dulcolax are stimulant laxatives. For patients who prefer natural therapies, we point out that senna is derived from plants.

 

In our experience, patients usually have tried bisacodyl before seeking treatment for constipation. Although bisacodyl may be effective for some patients, others may need something stronger. Many gastroenterologists prefer prescribing osmotic or prescription laxatives.

Step 4. Osmotic laxatives generally are liquids, including magnesium hydroxide, polyethylene glycol solution, and the prescription agent lactulose. Magnesium hydroxide is inexpensive and can be taken chronically.

Algorithm

A stepwise approach to managing constipation

Step 1
Recommendation	Comments
Increase activity or daily walking	Not rigorously studied in constipated patients; exercise is associated with decreased orocecal transit time15
Increase fluid intake	Not rigorously studied in constipated patients8
Increase dietary fiber intake	Not rigorously studied in constipated patients8
↓
Step 2
Recommendation	Comments
Fiber supplements	Psyllium compounds may be superior to methylcellulose, polycarbophil, and bran11
↓
Step 3
Recommendation	Comments
Over-the-counter laxative pills	Senna compounds are derived from plants
↓
Step 4
Recommendation	Comments
Over-the-counter laxative solutions	Milk of Magnesia is very inexpensive
↓
Step 5
Recommendation	Comments
Prescription laxatives	Lubiprostone causes fetal loss in animals; tegaserod is available only under a treatment investigational new drug protocol

Table 2

Commonly used laxatives: Mechanisms of action

Category	Agents
Bulk-forming	Methylcellulose (Citrucel), polycarbophil (Equalactin, Mitrolan, others), psyllium (Fiberall, Metamucil, others)
Lubricating	Glycerin (Sani-Supp), magnesium hydroxide and mineral oil (Magnolax), mineral oil (Fleet Mineral Oil, Zymenol, others)
Stool softener	Docusate sodium (Colace)
Osmotic	Magnesium hydroxide (Milk of Magnesia), polyethylene glycol (MiraLax), lactulose* (Cholac Syrup, Constulose, others), lubiprostone* (Amitiza)
Stimulant	Bisacodyl (Correctol, Dulcolax, others), castor oil (Alphamul, Emulsoil, others), senna/sennosides (Ex-Lax, Senokot, others), sodium bicarbonate and potassium bitartrate (Ceo-Two evacuant)
* Available by prescription only
Source: Reference 8

Prescription medications

Tegaserod is a partial 5-HT4 agonist and stimulator of GI motility and secretion. It also decreases visceral sensitivity.¹⁶ Tegaserod’s manufacturer voluntarily withdrew the drug from the market because it may increase risk of cardiovascular ischemic events, including angina, heart attack, and stroke. Tegaserod is available only under a treatment investigational new drug (IND) protocol that includes obtaining approval from a local institutional review board. We recommend that psychiatrists should not prescribe tegaserod but refer patients to experienced gastroenterologists or other GI specialists.

Lubiprostone is a selective chloride channel activator that works only in the gut and results in net fluid excretion and increased stool frequency. The molecule is a prostaglandin derivative and is poorly absorbed.¹⁷

Because lubiprostone has been shown to cause fetal loss in animals (at the equivalent of 2 and 6 times the recommended human dose), women of reproductive age should use contraception while taking lubiprostone and carefully consider the risks and benefits of lubiprostone use during pregnancy.

CASE CONTINUED: Finding an effective strategy

The psychiatrist prescribes lubiprostone, 24 mcg bid, but Mr. W once again complains of the expense and says the drug does not work well. He quickly returns to his intermittent use of magnesium hydroxide tablets and occasionally takes bisacodyl tablets.

To address Mr. W’s OCD, the psychiatrist adds risperidone, 0.5 mg bid, to Mr. W’s regimen. He has a modest response in OCD symptoms—30% of his day is now symptom- free— without worsening his constipation.

Probiotics and prebiotics

Emerging therapies for constipation include probiotics and prebiotics, which attempt to alter the gut flora and milieu. The primary bacterial agents are Lactobacillus species and Bifidobacterium species. At least one probiotic Bifidobacterium product—Activia—is being marketed in the United States as a fortified yogurt.

Because limited clinical data are available on the effect of probiotics and prebiotics on constipation, their routine use is not indicated. However, patients who prefer not to take medication may wish to try them. Because these agents are active cells, advise patients to purchase a supplement with “live and active” cultures. Supplements that are shipped, stored, or sold at room temperature likely contain very few (if any) live cultures.

Investigational medications. Renzapride is a 5HT4 receptor agonist and 5HT3 receptor antagonist that has shown promise in a pilot study¹⁸ and is in phase III trials. Linaclotide is a peptide that activates chloride and bicarbonate secretion in the gut and may reduce visceral hypersensitivity. It too has shown promise in a pilot study.¹⁹

Related resources

• Rome Foundation. Functional gastrointestinal disorders. www.romecriteria.org.
  
• Bleser S, Brunton S, Carmichael B, et al. Management of chronic constipation: recommendations from a consensus panel. J Fam Pract 2005;54(8):691-8.
  

Drug brand name

• Amitriptyline • Elavil, Endep
  
• Chlorpromazine • Thorazine
  
• Clomipramine • Anafranil
  
• Clozapine • Clozaril
  
• Duloxetine • Cymbalta
  
• Fluvoxamine • Luvox
  
• Lactulose • Cholac Syrup, Constulose, others
  
• Lubiprostone • Amitiza
  
• Mirtazapine • Remeron
  
• Olanzapine • Zyprexa
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Tegaserod • Zelnorm
  

Disclosure

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

Acknowledgment

This project was partially supported by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality.

Mr. W, age 50, presents to the psychiatry clinic with obsessive-compulsive disorder (OCD) symptoms. At his first interview, he says he spends every waking hour obsessing over whether or not he does things “right.” These thoughts force him to compulsively check and recheck everything he does, from simple body movements to complex computer tasks.

He has a history of OCD since age 8, with intermittent episodes of major depression. He reports that several years ago, he had a “miraculous” response to clomipramine for several weeks but has not responded to any other medication. Nevertheless, he continues taking clomipramine, 50 mg/d, hoping that it “might eventually do some good.” He adds that when he tried to increase the dose, he suffered from “terrible constipation” despite regular use of a methylcellulose fiber supplement.

The psychiatrist discontinues clomipramine and starts Mr. W on duloxetine, 90 mg/d. At the next visit, Mr. W complains that his constipation is much worse, so the psychiatrist decreases duloxetine to 60 mg/d, which eventually provides some relief. Because Mr. W has minimal response to duloxetine after 6 months, the psychiatrist adds olanzapine. Although this agent is anticholinergic, the patient had responded to a previous trial of this antipsychotic. Soon after, Mr. W experiences severe constipation.

Psychiatric patients face a host of potential causes of constipation, including:

• use of psychotropics and other medications
  
• decreased eating or physical activity as a result of depression or another psychiatric disorder
  
• medical comorbidities that decrease gastrointestinal (GI) motility.
  

Constipation carries a tremendous cost in terms of resources and quality of life.^1-7 This condition also can make patients stop taking medications. You can help patients avoid the discomfort and quality-of-life consequences by promptly diagnosing constipation and following a 5-step treatment algorithm that has shown value in our clinical practice.

Box 1

What to look for

When evaluating a patient who complains of constipation, first determine what he or she means by “constipation.” Do not rely on frequency of bowel movements as the only criterion for diagnosis. Under Rome Committee for Functional Gastrointestinal Disorders guidelines for diagnosis of chronic (or functional) constipation, patients who move their bowels daily may meet criteria for chronic constipation if they experience straining, incomplete evacuation, or other symptoms (Box 1).⁸

Many patients who complain of constipation have daily, regular bowel movements that produce hard, difficult-to-pass stool or require straining or manual maneuvers. Take a careful history including:

• stool frequency and quality
  
• straining
  
• manual maneuvers (disimpaction or manual pelvic floor support)
  
• sensation of blockage or incomplete evacuation.
  

In women, take a history of childbirth and obstetric or gynecologic surgery. Also determine the timing of symptom onset related to any new prescription or over-the-counter medications or supplements.

‘Alarm’ symptoms. For psychiatrists, the most important part of the Rome guidelines are the “alarm” symptoms:

• age ≥50 years
  
• family history of colon cancer or polyps
  
• family history of inflammatory bowel disease (ulcerative colitis or Crohn’s disease)
  
• rectal bleeding, anemia
  
• weight loss >10 pounds
  
• new onset of chronic constipation without apparent cause in an elderly patient
  
• severe, persistent constipation refractory to conservative management.⁹
  

Refer a patient with any of these symptoms to a specialist for endoscopic or clinical evaluation. Follow United States Preventative Services Task Force recommendations for colorectal cancer screening of all patients age ≥50 (Table 1).¹⁰

Table 1

Colorectal cancer screening recommendations*

Test	Frequency
Fecal occult blood testing (FOBT)	Annually
Sigmoidoscopy	Every 5 years
FOBT and sigmoidoscopy	Every 5 years
Double contrast barium enema	Every 5 years
Colonoscopy	Every 10 years
* For patients age=50. For higher-risk patients, it is reasonable to begin screening at a younger age
Source: Reference 10

Determining the cause

Common causes of constipation include altered visceral sensitivity, decreased GI motility, alterations in pelvic and anorectal musculature, and alterations in the enteric nervous system. Systemic causes are less common and include electrolyte abnormalities (hypercalcemia and hypokalemia) and endocrine disorders (hypothyroidism and diabetes mellitus).

Some patients’ constipation is caused by involuntarily contracting the pelvic floor muscles or suppressing the urge to defecate (Box 2).^1,11,12 Suspect this in patients who strain repeatedly to pass soft or liquid stool.

Medication side effects are probably the most common constipation cause psychiatrists will encounter. Many psychotropics have anticholinergic effects that decrease GI motility and cause constipation. The most commonly implicated drugs are:

 

• older tricyclic antidepressants (such as amitriptyline)
  
• antipsychotics.
  

Among antipsychotics, clozapine, thioridazine, olanzapine, and chlorpromazine probably have the greatest anticholinergic effects.¹³ Many selective serotonin reuptake inhibitors also can cause constipation.

Box 2

Older psychiatric patients with constipation may be taking medications for medical conditions—particularly alpha, beta, and calcium channel blockers—that may have synergistic effects on slowing bowel motility. For these patients you may not have the luxury of making multiple medication changes. The correct management strategy may be to add docusate sodium, a stool softener available over-the-counter as Colace.

Other psychiatric-related causes. Patients with depression may experience decreased stool output because of a lack of food intake or physical activity. These causes may be effectively addressed by treating the depression.

Give special consideration to patients with eating disorders and those who routinely use laxatives. A patient who is not eating will not produce the same amount of stool as one who eats regularly.

Constipated patients may require escalating doses of laxatives to obtain symptom relief; this does not constitute laxative abuse but rather tachyphylaxis. Chronic laxative use has not been shown to permanently decrease colonic motility,¹⁴ but patients who use laxatives chronically may have altered expectations of what is normal.

CASE CONTINUED: Recurring symptoms

After discontinuing Mr. W’s olanzapine and duloxetine, the psychiatrist prescribes polyethylene glycol solution (MiraLax) and instructs Mr. W to increase his daily fluid and fiber intake. Although the solution works well, Mr. W complains of the cost. He then resumes methyl cellulose and starts taking magnesium hydroxide chewable tablets (Milk of Magnesia) every 2 to 4 days as needed for constipation.

The psychiatrist prescribes mirtazapine for OCD symptoms, but soon stops this regimen because Mr. W complains of worsening constipation. Next Mr. W is started on fluvoxamine, which he had tried briefly many years before. The dosage is gradually titrated to 150 mg/d. Although Mr. W’s OCD improves somewhat, he complains of agitation and once again of worsening constipation.

Treatment algorithm

To minimize trial and error, we use a stepwise approach to treating constipation (Algorithm).^8,11,15 Although many standard recommendations have not been evaluated in large randomized controlled trials, they are supported by decades of observed actions among clinicians and thus remain valuable.

Multiple nonprescription agents are available to treat constipation, including:

• bulking agents (fiber supplements)
  
• lubricating agents
  
• stool softening agents
  
• stimulant and osmotic laxatives (Table 2).⁸
  

Advise patients that they may need to try multiple agents to find one that is tolerable and effective.

Steps 1 & 2. When initial attempts at increasing physical activity, fluid, and dietary fiber fail to yield a response, fiber supplements are commonly used as a second step in managing constipation. We advocate beginning with a supplement that contains psyllium—such as Fiber-all or Metamucil—because psyllium has been shown to increase stool frequency. Supplements that contain methylcellulose (Citrucel), polycarbophil (such as Equalactin and Mitrolan), or bran have either not shown efficacy or have not been studied rigorously enough to merit recommendation.¹⁰ Some patients respond to other fiber products, but start a fibernaïve patient with a psyllium-containing supplement.

Fiber supplements may cause increased gas and bloating, so start at a low dose and gradually increase over several weeks to mitigate these side effects.

Step 3. If fiber supplements fail, try a stimulant or osmotic laxative. Senna compounds such as Ex-Lax and Senokot and bisacodyl products such as Correctol and Dulcolax are stimulant laxatives. For patients who prefer natural therapies, we point out that senna is derived from plants.

 

In our experience, patients usually have tried bisacodyl before seeking treatment for constipation. Although bisacodyl may be effective for some patients, others may need something stronger. Many gastroenterologists prefer prescribing osmotic or prescription laxatives.

Step 4. Osmotic laxatives generally are liquids, including magnesium hydroxide, polyethylene glycol solution, and the prescription agent lactulose. Magnesium hydroxide is inexpensive and can be taken chronically.

Algorithm

A stepwise approach to managing constipation

Step 1
Recommendation	Comments
Increase activity or daily walking	Not rigorously studied in constipated patients; exercise is associated with decreased orocecal transit time15
Increase fluid intake	Not rigorously studied in constipated patients8
Increase dietary fiber intake	Not rigorously studied in constipated patients8
↓
Step 2
Recommendation	Comments
Fiber supplements	Psyllium compounds may be superior to methylcellulose, polycarbophil, and bran11
↓
Step 3
Recommendation	Comments
Over-the-counter laxative pills	Senna compounds are derived from plants
↓
Step 4
Recommendation	Comments
Over-the-counter laxative solutions	Milk of Magnesia is very inexpensive
↓
Step 5
Recommendation	Comments
Prescription laxatives	Lubiprostone causes fetal loss in animals; tegaserod is available only under a treatment investigational new drug protocol

Table 2

Commonly used laxatives: Mechanisms of action

Category	Agents
Bulk-forming	Methylcellulose (Citrucel), polycarbophil (Equalactin, Mitrolan, others), psyllium (Fiberall, Metamucil, others)
Lubricating	Glycerin (Sani-Supp), magnesium hydroxide and mineral oil (Magnolax), mineral oil (Fleet Mineral Oil, Zymenol, others)
Stool softener	Docusate sodium (Colace)
Osmotic	Magnesium hydroxide (Milk of Magnesia), polyethylene glycol (MiraLax), lactulose* (Cholac Syrup, Constulose, others), lubiprostone* (Amitiza)
Stimulant	Bisacodyl (Correctol, Dulcolax, others), castor oil (Alphamul, Emulsoil, others), senna/sennosides (Ex-Lax, Senokot, others), sodium bicarbonate and potassium bitartrate (Ceo-Two evacuant)
* Available by prescription only
Source: Reference 8

Prescription medications

Tegaserod is a partial 5-HT4 agonist and stimulator of GI motility and secretion. It also decreases visceral sensitivity.¹⁶ Tegaserod’s manufacturer voluntarily withdrew the drug from the market because it may increase risk of cardiovascular ischemic events, including angina, heart attack, and stroke. Tegaserod is available only under a treatment investigational new drug (IND) protocol that includes obtaining approval from a local institutional review board. We recommend that psychiatrists should not prescribe tegaserod but refer patients to experienced gastroenterologists or other GI specialists.

Lubiprostone is a selective chloride channel activator that works only in the gut and results in net fluid excretion and increased stool frequency. The molecule is a prostaglandin derivative and is poorly absorbed.¹⁷

Because lubiprostone has been shown to cause fetal loss in animals (at the equivalent of 2 and 6 times the recommended human dose), women of reproductive age should use contraception while taking lubiprostone and carefully consider the risks and benefits of lubiprostone use during pregnancy.

CASE CONTINUED: Finding an effective strategy

The psychiatrist prescribes lubiprostone, 24 mcg bid, but Mr. W once again complains of the expense and says the drug does not work well. He quickly returns to his intermittent use of magnesium hydroxide tablets and occasionally takes bisacodyl tablets.

To address Mr. W’s OCD, the psychiatrist adds risperidone, 0.5 mg bid, to Mr. W’s regimen. He has a modest response in OCD symptoms—30% of his day is now symptom- free— without worsening his constipation.

Probiotics and prebiotics

Emerging therapies for constipation include probiotics and prebiotics, which attempt to alter the gut flora and milieu. The primary bacterial agents are Lactobacillus species and Bifidobacterium species. At least one probiotic Bifidobacterium product—Activia—is being marketed in the United States as a fortified yogurt.

Because limited clinical data are available on the effect of probiotics and prebiotics on constipation, their routine use is not indicated. However, patients who prefer not to take medication may wish to try them. Because these agents are active cells, advise patients to purchase a supplement with “live and active” cultures. Supplements that are shipped, stored, or sold at room temperature likely contain very few (if any) live cultures.

Investigational medications. Renzapride is a 5HT4 receptor agonist and 5HT3 receptor antagonist that has shown promise in a pilot study¹⁸ and is in phase III trials. Linaclotide is a peptide that activates chloride and bicarbonate secretion in the gut and may reduce visceral hypersensitivity. It too has shown promise in a pilot study.¹⁹

Related resources

• Rome Foundation. Functional gastrointestinal disorders. www.romecriteria.org.
  
• Bleser S, Brunton S, Carmichael B, et al. Management of chronic constipation: recommendations from a consensus panel. J Fam Pract 2005;54(8):691-8.
  

Drug brand name

• Amitriptyline • Elavil, Endep
  
• Chlorpromazine • Thorazine
  
• Clomipramine • Anafranil
  
• Clozapine • Clozaril
  
• Duloxetine • Cymbalta
  
• Fluvoxamine • Luvox
  
• Lactulose • Cholac Syrup, Constulose, others
  
• Lubiprostone • Amitiza
  
• Mirtazapine • Remeron
  
• Olanzapine • Zyprexa
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Tegaserod • Zelnorm
  

Disclosure

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

Acknowledgment

This project was partially supported by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality.

Partial hospitalization programs (PHPs) are a good alternative to inpatient treatment for many patients who do not pose an imminent risk of harm to themselves or others.¹ PHPs provide:

• equivalent or superior recovery-based care at a lower cost, and patients are satisfied with the treatment²
  
• clinical services such as crisis stabilization, symptom management, and structured socialization within a stable therapeutic milieu, without the increased dependence on clinicians and loss of function of hospitalization.³
  

PHPs can be used in lieu of an inpatient admission or as an intermediate step to shorten a patient’s inpatient stay. Close proximity to and coordination with an inpatient setting can facilitate transition of care and may reduce patient drop-out rates. In addition, PHPs often allow extended evaluation of psychiatric symptoms and functional ability and may help you reach difficult-to-engage patients. Keeping patients in the community might help preserve patients’ self-esteem.

PHPs focus on behavioral activation skills and encourage patients to participate in treatment planning and intervention. Using a “pressure cooker” technique, treatment encourages patients to mobilize themselves within a limited time frame.

To determine which of your patients are likely to benefit from PHPs, we use the mnemonic MOTIVATES:

Motivated. Patients who are motivated to participate in daily programs are the best candidates for this level of care.

Organized. Individuals must be able to benefit from psychoeducation and skills-building groups. Patients who are grossly psychotic or delirious are not candidates for PHPs.

Tolerate a milieu or group setting. Floridly antisocial or manic patients may be disruptive and could negatively affect the milieu.

Interested in recovery. A patient who does not want to get well or stay sober usually relapses and drops out of treatment.

Verbal. Patients who can verbalize their thoughts and feelings tend to do better, although this skill can be developed while in a PHP.

Ability. Patients must be able to participate in their vocational and social rehabilitation.

Treatment adherent. Patients who are not adherent often don’t improve in PHPs.

Experience. Look for patients who have had positive experiences with milieu treatment settings.

Safe. PHP patients must not pose an acute risk of harming themselves or others.

The Association of Ambulatory Behavioral Health encourages PHPs to embrace the concept of recovery, which encourages the patient to be an active and empowered participant in treatment. Instilling hope is one of the cornerstones of the recovery movement.

References

1. Horvitz-Lennon M, Normand SL, Gaccione P, Frank RG. Partial versus full hospitalization for adults in psychiatric distress: a systematic review of the published literature (1957-1997). Am J Psychiatry 2001;158:676-85.

2. Hoge MA, Davidson L, Hill WL, et al. The promise of partial hospitalization: a reassessment. Hosp Community Psychiatry 1992;43:345-54.

3. Dick P, Cameron L, Cohen D, et al. Day and full time psychiatric treatment: a controlled comparison. Br J Psychiatry 1985;147:250-3.

Partial hospitalization programs (PHPs) are a good alternative to inpatient treatment for many patients who do not pose an imminent risk of harm to themselves or others.¹ PHPs provide:

• equivalent or superior recovery-based care at a lower cost, and patients are satisfied with the treatment²
  
• clinical services such as crisis stabilization, symptom management, and structured socialization within a stable therapeutic milieu, without the increased dependence on clinicians and loss of function of hospitalization.³
  

PHPs can be used in lieu of an inpatient admission or as an intermediate step to shorten a patient’s inpatient stay. Close proximity to and coordination with an inpatient setting can facilitate transition of care and may reduce patient drop-out rates. In addition, PHPs often allow extended evaluation of psychiatric symptoms and functional ability and may help you reach difficult-to-engage patients. Keeping patients in the community might help preserve patients’ self-esteem.

PHPs focus on behavioral activation skills and encourage patients to participate in treatment planning and intervention. Using a “pressure cooker” technique, treatment encourages patients to mobilize themselves within a limited time frame.

To determine which of your patients are likely to benefit from PHPs, we use the mnemonic MOTIVATES:

Motivated. Patients who are motivated to participate in daily programs are the best candidates for this level of care.

Organized. Individuals must be able to benefit from psychoeducation and skills-building groups. Patients who are grossly psychotic or delirious are not candidates for PHPs.

Tolerate a milieu or group setting. Floridly antisocial or manic patients may be disruptive and could negatively affect the milieu.

Interested in recovery. A patient who does not want to get well or stay sober usually relapses and drops out of treatment.

Verbal. Patients who can verbalize their thoughts and feelings tend to do better, although this skill can be developed while in a PHP.

Ability. Patients must be able to participate in their vocational and social rehabilitation.

Treatment adherent. Patients who are not adherent often don’t improve in PHPs.

Experience. Look for patients who have had positive experiences with milieu treatment settings.

Safe. PHP patients must not pose an acute risk of harming themselves or others.

The Association of Ambulatory Behavioral Health encourages PHPs to embrace the concept of recovery, which encourages the patient to be an active and empowered participant in treatment. Instilling hope is one of the cornerstones of the recovery movement.

References

1. Horvitz-Lennon M, Normand SL, Gaccione P, Frank RG. Partial versus full hospitalization for adults in psychiatric distress: a systematic review of the published literature (1957-1997). Am J Psychiatry 2001;158:676-85.

2. Hoge MA, Davidson L, Hill WL, et al. The promise of partial hospitalization: a reassessment. Hosp Community Psychiatry 1992;43:345-54.

3. Dick P, Cameron L, Cohen D, et al. Day and full time psychiatric treatment: a controlled comparison. Br J Psychiatry 1985;147:250-3.

Partial hospitalization programs (PHPs) are a good alternative to inpatient treatment for many patients who do not pose an imminent risk of harm to themselves or others.¹ PHPs provide:

• equivalent or superior recovery-based care at a lower cost, and patients are satisfied with the treatment²
  
• clinical services such as crisis stabilization, symptom management, and structured socialization within a stable therapeutic milieu, without the increased dependence on clinicians and loss of function of hospitalization.³
  

PHPs can be used in lieu of an inpatient admission or as an intermediate step to shorten a patient’s inpatient stay. Close proximity to and coordination with an inpatient setting can facilitate transition of care and may reduce patient drop-out rates. In addition, PHPs often allow extended evaluation of psychiatric symptoms and functional ability and may help you reach difficult-to-engage patients. Keeping patients in the community might help preserve patients’ self-esteem.

PHPs focus on behavioral activation skills and encourage patients to participate in treatment planning and intervention. Using a “pressure cooker” technique, treatment encourages patients to mobilize themselves within a limited time frame.

To determine which of your patients are likely to benefit from PHPs, we use the mnemonic MOTIVATES:

Motivated. Patients who are motivated to participate in daily programs are the best candidates for this level of care.

Organized. Individuals must be able to benefit from psychoeducation and skills-building groups. Patients who are grossly psychotic or delirious are not candidates for PHPs.

Tolerate a milieu or group setting. Floridly antisocial or manic patients may be disruptive and could negatively affect the milieu.

Interested in recovery. A patient who does not want to get well or stay sober usually relapses and drops out of treatment.

Verbal. Patients who can verbalize their thoughts and feelings tend to do better, although this skill can be developed while in a PHP.

Ability. Patients must be able to participate in their vocational and social rehabilitation.

Treatment adherent. Patients who are not adherent often don’t improve in PHPs.

Experience. Look for patients who have had positive experiences with milieu treatment settings.

Safe. PHP patients must not pose an acute risk of harming themselves or others.

The Association of Ambulatory Behavioral Health encourages PHPs to embrace the concept of recovery, which encourages the patient to be an active and empowered participant in treatment. Instilling hope is one of the cornerstones of the recovery movement.

References

1. Horvitz-Lennon M, Normand SL, Gaccione P, Frank RG. Partial versus full hospitalization for adults in psychiatric distress: a systematic review of the published literature (1957-1997). Am J Psychiatry 2001;158:676-85.

2. Hoge MA, Davidson L, Hill WL, et al. The promise of partial hospitalization: a reassessment. Hosp Community Psychiatry 1992;43:345-54.

3. Dick P, Cameron L, Cohen D, et al. Day and full time psychiatric treatment: a controlled comparison. Br J Psychiatry 1985;147:250-3.

As a psychopharmacology consultant, I often encounter bits of received wisdom that do not square with results of controlled studies. Although all these “myths” contain a grain of truth, their uncritical acceptance can be a barrier to effective care.

1 Dual-acting antidepressants are more effective than serotonergic agents.

Although some serotonin/norepinephrine reuptake inhibitors may be modestly more effective than some selective serotonin reuptake inhibitors (SSRIs), no randomized studies show that one class of antidepressants is clearly superior to another. The overall difference in remission rates between venlafaxine and SSRIs—about 6% favoring venlafaxine—is not robust.¹

2 Lithium is not as effective as divalproex for treating rapid-cycling bipolar disorder.

Rapid-cycling bipolar disorder can indicate reduced drug responsiveness, but lithium should not be disregarded. The relapse rate into any mood episode among rapid cyclers is not significantly different among patients maintained on lithium vs valproate,² though concomitant antidepressant treatment complicates some studies.

3 Psychotropics with short elimination half-lives need to be administered 2 or more times a day.

This statement may be true for some patients taking short-acting benzodiazepines for panic disorder or psychostimulants for attention- deficit/hyperactivity disorder. However, no randomized, head-to-head studies show that antidepressants or antipsychotics with half-lives 3 Antipsychotic effects probably persist at dopamine-2 receptors even at trough blood levels.

4 Tardive dyskinesia (TD) is not a problem with atypical antipsychotics.

Atypical or second-generation antipsychotics (SGAs) are associated with TD rates approximately one-tenth to one-half that of first-generation antipsychotics. But TD can occur with atypicals, particularly in very old and very young patients. Some data indicate TD rates >10% in African-American children taking SGAs.⁴

5 Stimulants should never be combined with a monoamine oxidase inhibitor (MAOI) because a dangerous hypertensive reaction is likely.

No controlled studies or case reports show that carefully adding a psychostimulant—such as methylphenidate, 5 to 10 mg/d—to an MAOI leads to serious hypertensive or other life-threatening reactions.⁵ Nevertheless, a careful risk-benefit assessment and close monitoring are indicated when prescribing this combination.

6 Antidepressants are effective and necessary in maintenance treatment of bipolar disorder.

Most recent studies find little benefit from adjunctive antidepressants in maintenance treatment of bipolar disorder.⁶ Although most stabilized bipolar patients don’t need an antidepressant, some may experience depressive relapse when adjunctive antidepressants are discontinued.

7 Co-administered mood stabilizers prevent antidepressant-induced ‘switching’ into bipolar mania.

It is not clear that mood stabilizers as a class provide reliable protection against antidepressant-induced switching, though lithium may offer more protection than anticonvulsants.⁷ Even if switching is not caused by antidepressants,⁶ irritability, insomnia, and cycle acceleration may occur in susceptible patients.

As a psychopharmacology consultant, I often encounter bits of received wisdom that do not square with results of controlled studies. Although all these “myths” contain a grain of truth, their uncritical acceptance can be a barrier to effective care.

1 Dual-acting antidepressants are more effective than serotonergic agents.

Although some serotonin/norepinephrine reuptake inhibitors may be modestly more effective than some selective serotonin reuptake inhibitors (SSRIs), no randomized studies show that one class of antidepressants is clearly superior to another. The overall difference in remission rates between venlafaxine and SSRIs—about 6% favoring venlafaxine—is not robust.¹

2 Lithium is not as effective as divalproex for treating rapid-cycling bipolar disorder.

Rapid-cycling bipolar disorder can indicate reduced drug responsiveness, but lithium should not be disregarded. The relapse rate into any mood episode among rapid cyclers is not significantly different among patients maintained on lithium vs valproate,² though concomitant antidepressant treatment complicates some studies.

3 Psychotropics with short elimination half-lives need to be administered 2 or more times a day.

This statement may be true for some patients taking short-acting benzodiazepines for panic disorder or psychostimulants for attention- deficit/hyperactivity disorder. However, no randomized, head-to-head studies show that antidepressants or antipsychotics with half-lives 3 Antipsychotic effects probably persist at dopamine-2 receptors even at trough blood levels.

4 Tardive dyskinesia (TD) is not a problem with atypical antipsychotics.

Atypical or second-generation antipsychotics (SGAs) are associated with TD rates approximately one-tenth to one-half that of first-generation antipsychotics. But TD can occur with atypicals, particularly in very old and very young patients. Some data indicate TD rates >10% in African-American children taking SGAs.⁴

5 Stimulants should never be combined with a monoamine oxidase inhibitor (MAOI) because a dangerous hypertensive reaction is likely.

No controlled studies or case reports show that carefully adding a psychostimulant—such as methylphenidate, 5 to 10 mg/d—to an MAOI leads to serious hypertensive or other life-threatening reactions.⁵ Nevertheless, a careful risk-benefit assessment and close monitoring are indicated when prescribing this combination.

6 Antidepressants are effective and necessary in maintenance treatment of bipolar disorder.

Most recent studies find little benefit from adjunctive antidepressants in maintenance treatment of bipolar disorder.⁶ Although most stabilized bipolar patients don’t need an antidepressant, some may experience depressive relapse when adjunctive antidepressants are discontinued.

7 Co-administered mood stabilizers prevent antidepressant-induced ‘switching’ into bipolar mania.

It is not clear that mood stabilizers as a class provide reliable protection against antidepressant-induced switching, though lithium may offer more protection than anticonvulsants.⁷ Even if switching is not caused by antidepressants,⁶ irritability, insomnia, and cycle acceleration may occur in susceptible patients.

As a psychopharmacology consultant, I often encounter bits of received wisdom that do not square with results of controlled studies. Although all these “myths” contain a grain of truth, their uncritical acceptance can be a barrier to effective care.

1 Dual-acting antidepressants are more effective than serotonergic agents.

Although some serotonin/norepinephrine reuptake inhibitors may be modestly more effective than some selective serotonin reuptake inhibitors (SSRIs), no randomized studies show that one class of antidepressants is clearly superior to another. The overall difference in remission rates between venlafaxine and SSRIs—about 6% favoring venlafaxine—is not robust.¹

2 Lithium is not as effective as divalproex for treating rapid-cycling bipolar disorder.

Rapid-cycling bipolar disorder can indicate reduced drug responsiveness, but lithium should not be disregarded. The relapse rate into any mood episode among rapid cyclers is not significantly different among patients maintained on lithium vs valproate,² though concomitant antidepressant treatment complicates some studies.

3 Psychotropics with short elimination half-lives need to be administered 2 or more times a day.

This statement may be true for some patients taking short-acting benzodiazepines for panic disorder or psychostimulants for attention- deficit/hyperactivity disorder. However, no randomized, head-to-head studies show that antidepressants or antipsychotics with half-lives 3 Antipsychotic effects probably persist at dopamine-2 receptors even at trough blood levels.

4 Tardive dyskinesia (TD) is not a problem with atypical antipsychotics.

Atypical or second-generation antipsychotics (SGAs) are associated with TD rates approximately one-tenth to one-half that of first-generation antipsychotics. But TD can occur with atypicals, particularly in very old and very young patients. Some data indicate TD rates >10% in African-American children taking SGAs.⁴

5 Stimulants should never be combined with a monoamine oxidase inhibitor (MAOI) because a dangerous hypertensive reaction is likely.

No controlled studies or case reports show that carefully adding a psychostimulant—such as methylphenidate, 5 to 10 mg/d—to an MAOI leads to serious hypertensive or other life-threatening reactions.⁵ Nevertheless, a careful risk-benefit assessment and close monitoring are indicated when prescribing this combination.

6 Antidepressants are effective and necessary in maintenance treatment of bipolar disorder.

Most recent studies find little benefit from adjunctive antidepressants in maintenance treatment of bipolar disorder.⁶ Although most stabilized bipolar patients don’t need an antidepressant, some may experience depressive relapse when adjunctive antidepressants are discontinued.

7 Co-administered mood stabilizers prevent antidepressant-induced ‘switching’ into bipolar mania.

It is not clear that mood stabilizers as a class provide reliable protection against antidepressant-induced switching, though lithium may offer more protection than anticonvulsants.⁷ Even if switching is not caused by antidepressants,⁶ irritability, insomnia, and cycle acceleration may occur in susceptible patients.

Persons with antisocial personality disorder display a disregard for the rights of others that can put them at odds with the legal system (Table). Those charged with or convicted of domestic battery, child abuse, or sexual assault often are referred for psychiatric evaluation pretrial, post-conviction, or during incarceration. Courts also may require psychotherapy in lieu of incarceration or after release.

Antisocial personality disorder differs from psychopathy, which indicates a more severe form of sociopathy. The “psychopath” is almost entirely bereft of superego or conscience and often displays sadistic traits. Antisocial personality disorder and psychopathy often are used interchangeably, however, and the pitfalls I describe apply to both.

Table

DSM-IV-TR criteria for antisocial personality disorder

Antisocial individuals display a pervasive pattern of disregard for and violation of the rights of others as indicated by ≥3 of the following: failure to conform to social norms with respect to lawful behaviors—repeatedly performing acts that are grounds for arrest deceitfulness—repeated lying, use of aliases, or conning others for personal profit or pleasure impulsivity or failure to plan ahead irritability and aggressiveness—repeated physical fights or assaults reckless disregard for safety of self or others consistent irresponsibility—failure to sustain consistent work behavior or honor financial obligations lack of remorse—being indifferent to or rationalizing having hurt, mistreated, or stolen from another

Source: Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000

Remain skeptical

When evaluating patients with antisocial characteristics, be aware of the hazards specific to this diagnosis. Antisocial patients’ considerable “charm” and ability to appear ingenuous and sincere helps solicit sympathy, allowing them to convince victims to drop their guard, prosecutors to reduce charges, and judges to mitigate sentences. These manipulative patients are skilled at persuading clinicians that we are “working miracles”—which, unfortunately, can take very little effort—hoping to win a favorable evaluation for the judge, probation officer, or parole board.

Evaluating clinical progress in antisocial patients is difficult because improvement can be determined only by a continued lack of antisocial behavior. It might not be possible to know whether antisocial behavior is:

• continuing undetected
  
• has been temporarily checked (“laying low”)
  
• or if the patient’s personality truly has been transformed.
  

The last is least likely because personality characteristics are deeply ingrained. Such a transformation would require the patient’s honest acknowledgement of a need to change and take many years of treatment to achieve. Antisocial patients’ strong secondary gain—to mitigate the consequences of criminal behavior—demands skepticism of reported clinical progress.¹

5 treatment caveats

When treating antisocial patients, remaining vigilant to the inherent challenges of working with them, stay within strict boundaries, and keep therapy from going adrift.

• Avoid allowing the patient to engage you with fascinating stories. Such tales may be exaggerated, fabricated, or designed to manipulate, charm, or enthrall to distract you from your treatment goals. Antisocial patients might exhibit pseudologia fantastica, a form of pathological lying in which the individual—although not frankly delusional—believes his embellished claims² and is so convinced that he can easily persuade and distract the therapist.
  
• Neither accept nor reject the patient’s claim of innocence. Emphasize that you cannot determine innocence. Instead, point out that you will help the patient identify choices and actions that caused his present predicament. If your patient insists on blaming others, refocus the discussion on his actions and choices that created or facilitated the problem.
  
• Do not accept your patient’s apologies, claims of remorse, or promises to change. Point out that only victims can accept apologies. Likewise, emphasize that promises to change can only be made to oneself.
  
• Direct the patient’s attention away from you—your brilliance, talent, and empathy—and focus on the patient, his past poor choices, and how he can improve his choices going forward.
  
• Treat only the symptoms that can be treated, such as disordered mood, hallucinations, grandiose delusions, and substance abuse, without allowing them to become excuses for criminal behavior. Point out that most patients with depression, schizophrenia, alcoholism, or other mental illnesses do not commit crimes.³
  

Persons with antisocial personality disorder display a disregard for the rights of others that can put them at odds with the legal system (Table). Those charged with or convicted of domestic battery, child abuse, or sexual assault often are referred for psychiatric evaluation pretrial, post-conviction, or during incarceration. Courts also may require psychotherapy in lieu of incarceration or after release.

Antisocial personality disorder differs from psychopathy, which indicates a more severe form of sociopathy. The “psychopath” is almost entirely bereft of superego or conscience and often displays sadistic traits. Antisocial personality disorder and psychopathy often are used interchangeably, however, and the pitfalls I describe apply to both.

Table

DSM-IV-TR criteria for antisocial personality disorder

Antisocial individuals display a pervasive pattern of disregard for and violation of the rights of others as indicated by ≥3 of the following: failure to conform to social norms with respect to lawful behaviors—repeatedly performing acts that are grounds for arrest deceitfulness—repeated lying, use of aliases, or conning others for personal profit or pleasure impulsivity or failure to plan ahead irritability and aggressiveness—repeated physical fights or assaults reckless disregard for safety of self or others consistent irresponsibility—failure to sustain consistent work behavior or honor financial obligations lack of remorse—being indifferent to or rationalizing having hurt, mistreated, or stolen from another

Source: Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000

Remain skeptical

When evaluating patients with antisocial characteristics, be aware of the hazards specific to this diagnosis. Antisocial patients’ considerable “charm” and ability to appear ingenuous and sincere helps solicit sympathy, allowing them to convince victims to drop their guard, prosecutors to reduce charges, and judges to mitigate sentences. These manipulative patients are skilled at persuading clinicians that we are “working miracles”—which, unfortunately, can take very little effort—hoping to win a favorable evaluation for the judge, probation officer, or parole board.

Evaluating clinical progress in antisocial patients is difficult because improvement can be determined only by a continued lack of antisocial behavior. It might not be possible to know whether antisocial behavior is:

• continuing undetected
  
• has been temporarily checked (“laying low”)
  
• or if the patient’s personality truly has been transformed.
  

The last is least likely because personality characteristics are deeply ingrained. Such a transformation would require the patient’s honest acknowledgement of a need to change and take many years of treatment to achieve. Antisocial patients’ strong secondary gain—to mitigate the consequences of criminal behavior—demands skepticism of reported clinical progress.¹

5 treatment caveats

When treating antisocial patients, remaining vigilant to the inherent challenges of working with them, stay within strict boundaries, and keep therapy from going adrift.

• Avoid allowing the patient to engage you with fascinating stories. Such tales may be exaggerated, fabricated, or designed to manipulate, charm, or enthrall to distract you from your treatment goals. Antisocial patients might exhibit pseudologia fantastica, a form of pathological lying in which the individual—although not frankly delusional—believes his embellished claims² and is so convinced that he can easily persuade and distract the therapist.
  
• Neither accept nor reject the patient’s claim of innocence. Emphasize that you cannot determine innocence. Instead, point out that you will help the patient identify choices and actions that caused his present predicament. If your patient insists on blaming others, refocus the discussion on his actions and choices that created or facilitated the problem.
  
• Do not accept your patient’s apologies, claims of remorse, or promises to change. Point out that only victims can accept apologies. Likewise, emphasize that promises to change can only be made to oneself.
  
• Direct the patient’s attention away from you—your brilliance, talent, and empathy—and focus on the patient, his past poor choices, and how he can improve his choices going forward.
  
• Treat only the symptoms that can be treated, such as disordered mood, hallucinations, grandiose delusions, and substance abuse, without allowing them to become excuses for criminal behavior. Point out that most patients with depression, schizophrenia, alcoholism, or other mental illnesses do not commit crimes.³
  

Persons with antisocial personality disorder display a disregard for the rights of others that can put them at odds with the legal system (Table). Those charged with or convicted of domestic battery, child abuse, or sexual assault often are referred for psychiatric evaluation pretrial, post-conviction, or during incarceration. Courts also may require psychotherapy in lieu of incarceration or after release.

Antisocial personality disorder differs from psychopathy, which indicates a more severe form of sociopathy. The “psychopath” is almost entirely bereft of superego or conscience and often displays sadistic traits. Antisocial personality disorder and psychopathy often are used interchangeably, however, and the pitfalls I describe apply to both.

Table

DSM-IV-TR criteria for antisocial personality disorder

Antisocial individuals display a pervasive pattern of disregard for and violation of the rights of others as indicated by ≥3 of the following: failure to conform to social norms with respect to lawful behaviors—repeatedly performing acts that are grounds for arrest deceitfulness—repeated lying, use of aliases, or conning others for personal profit or pleasure impulsivity or failure to plan ahead irritability and aggressiveness—repeated physical fights or assaults reckless disregard for safety of self or others consistent irresponsibility—failure to sustain consistent work behavior or honor financial obligations lack of remorse—being indifferent to or rationalizing having hurt, mistreated, or stolen from another

Source: Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000

Remain skeptical

When evaluating patients with antisocial characteristics, be aware of the hazards specific to this diagnosis. Antisocial patients’ considerable “charm” and ability to appear ingenuous and sincere helps solicit sympathy, allowing them to convince victims to drop their guard, prosecutors to reduce charges, and judges to mitigate sentences. These manipulative patients are skilled at persuading clinicians that we are “working miracles”—which, unfortunately, can take very little effort—hoping to win a favorable evaluation for the judge, probation officer, or parole board.

Evaluating clinical progress in antisocial patients is difficult because improvement can be determined only by a continued lack of antisocial behavior. It might not be possible to know whether antisocial behavior is:

• continuing undetected
  
• has been temporarily checked (“laying low”)
  
• or if the patient’s personality truly has been transformed.
  

The last is least likely because personality characteristics are deeply ingrained. Such a transformation would require the patient’s honest acknowledgement of a need to change and take many years of treatment to achieve. Antisocial patients’ strong secondary gain—to mitigate the consequences of criminal behavior—demands skepticism of reported clinical progress.¹

5 treatment caveats

When treating antisocial patients, remaining vigilant to the inherent challenges of working with them, stay within strict boundaries, and keep therapy from going adrift.

• Avoid allowing the patient to engage you with fascinating stories. Such tales may be exaggerated, fabricated, or designed to manipulate, charm, or enthrall to distract you from your treatment goals. Antisocial patients might exhibit pseudologia fantastica, a form of pathological lying in which the individual—although not frankly delusional—believes his embellished claims² and is so convinced that he can easily persuade and distract the therapist.
  
• Neither accept nor reject the patient’s claim of innocence. Emphasize that you cannot determine innocence. Instead, point out that you will help the patient identify choices and actions that caused his present predicament. If your patient insists on blaming others, refocus the discussion on his actions and choices that created or facilitated the problem.
  
• Do not accept your patient’s apologies, claims of remorse, or promises to change. Point out that only victims can accept apologies. Likewise, emphasize that promises to change can only be made to oneself.
  
• Direct the patient’s attention away from you—your brilliance, talent, and empathy—and focus on the patient, his past poor choices, and how he can improve his choices going forward.
  
• Treat only the symptoms that can be treated, such as disordered mood, hallucinations, grandiose delusions, and substance abuse, without allowing them to become excuses for criminal behavior. Point out that most patients with depression, schizophrenia, alcoholism, or other mental illnesses do not commit crimes.³
  

Mrs. S, age 50, has had relapsing-remitting multiple sclerosis (MS) for approximately 10 years. She describes her mood as “up and down” and is referred by her neurologist for psychiatric assessment of mood swings and possible depression. Fatigue limits her ability to work full-time, perform household duties, socialize with friends and family, and enjoy mental or physical exercise. In addition, her 18-year-old daughter—an important source of psychological support—is planning to leave home.

Mrs. S experienced depression 5 years ago during her divorce. She was prescribed paroxetine, 20 mg/d, and had a positive response. She took the medication for 6 months, then discontinued.

One-half of MS patients experience major depression in their lifetimes,¹ and the suicide rate is approximately doubled in MS patients compared with the general population.² Depression in MS patients often has an atypical presentation, with irritability and anger being as prominent as sadness.³ Not all emotional changes experienced by MS patients represent depressive disorders, however.

When evaluating MS patients who are struggling with depression, you can help them by diagnosing comorbid mood disorders, determining suicide risk, and providing psychological support as they cope with the impact of their illness.

MS disease course

MS is a disease of the brain and spinal cord, characterized by:

 

• inflammatory demyelination and gliosis
• neuronal and axonal loss
• a variety of presenting symptoms as different CNS regions are affected.

Focal areas of demyelination followed by a reactive gliosis cause white matter lesions in the brain, spinal cord, and optic nerve. Neurologic dysfunction can manifest as visual changes, spastic paresis, hypoesthesia and paresthesia, ataxia, and bowel and bladder dysfunction. MS presentation also can include optic neuritis and transverse myelitis. MS symptoms often are intensified by heat exposure.

After the initial episode, months or years may pass before additional neurologic symptoms appear. Based on its course, MS can be classified as:

 

• relapsing-remitting, when the disease does not progress between attacks
• secondary progressive, characterized by a gradually progressive course after an initial relapsing-remitting pattern
• primary progressive, when patients experience gradual progressive disability from symptom onset (Table 1).

Table 1

Clinical classification of multiple sclerosis (MS)

 

Type	Characteristics
Relapsing-remitting*	Symptoms appear during relapses, resolve during remissions, and do not progress between relapses
Secondary progressive	MS symptoms that previously followed a relapsing-remitting pattern steadily become more severe and progress without relapse
Primary progressive	Gradual progression from symptom onset, without relapses or remission
Clinically isolated syndrome	A single attack that may indicate MS has occurred—such as optic neuritis or transverse myelitis—but clinical requirements for the diagnosis have not been met
* Patients often progress from relapsing-remitting to secondary progressive MS

CASE CONTINUED: Progressing symptoms

Mrs. S has had multiple MS presentations, including optic neuritis, lower extremity weakness, balance problems, and urinary incontinence. Recently, her MS symptoms have gradually progressed even in the absence of attacks, and her diagnosis has been revised to secondary progressive MS.

During psychiatric evaluation, Mrs. S denies persistent changes in sleep or appetite. She describes fatigue that starts after physical exertion and increases as the day progresses. She denies feelings of worthlessness, helplessness, excessive guilt, and suicidal ideation and does not have a history of inappropriate anger or irritability.

Diagnosing depression in MS

Normal emotional adjustment to MS can include reactions to loss of function or changes in social or occupational roles. Further, MS patients—similar to non-MS patients—experience life changes and transitions not related to the illness, such as divorce or a grown child moving away. Emotional responses to life stressors often are self-limited but may warrant an adjustment disorder diagnosis if they are associated with excessive distress or substantial impairment in social, occupational, or academic functioning (Table 2).⁴

Table 2

Questions to consider when assessing MS patients for depression

 

Ask yourself	Reason
Are symptoms part of normal emotional changes?	Not all mood changes are pathologic or meet criteria for major depression
Is this an adjustment disorder?	Mood symptoms can be caused by a major stressor such as a recent diagnosis or personal loss
Is fatigue secondary to MS or depression?	MS typically causes fatigue after physical activity and heat exposure; fatigue early in the day points to depression
Are cognitive deficits related to MS or depression?	Negative thoughts point to depression whereas cognitive deficits may be caused by depression, MS, or both
Is this an atypical presentation?	MS patients may present with anger or irritability
Is this a pseudobulbar problem?	Patients with IEED might describe more concern about affect dysregulation than mood swings
MS: multiple sclerosis; IEED: involuntary emotional expression disorder

Female MS patients and those who report high stress or a family history of affective disorder may be more likely to develop clinical depression.⁵ Several studies have reported correlations between structural brain abnormalities and depression in MS. Feinstein et al

 

⁶ reported that extensive hyper intense lesion volume in the left medial inferior prefrontal region with atrophy affecting the dominant anterior temporal lobe was associated with major depression. However, a depression diagnosis in MS patients remains a clinical one that does not require brain imaging studies.

Lack of interest or enjoyment as a symptom of depression can be difficult to identify because MS can diminish enjoyment of some activities. Although patients with MS may need to change their activity patterns to accommodate their illness, the lack of enjoyment in all—or almost all—activities remains a valid indicator of depressive disorder.

MS treatment includes the use of disease-modifying medications such as interferon beta-1b and interferon beta-1a. Several years ago researchers were concerned that interferon beta might cause depression in MS patients based on reports of a suicide and attempted suicide during an early trial of interferon beta-1b in relapsing-remitting MS.⁷ Subsequent studies did not substantiate this concern, however (Box 1).^8,9

 

Overlapping symptoms such as fatigue and cognitive deterioration could complicate the diagnosis. Look for changing patterns of these symptoms and other signs of depression. Rating scales that do not emphasize fatigue and cognitive impairment—such as the Beck Depression Inventory¹⁰ and the Center for Epidemiologic Studies Depression Rating Scale¹¹—can help identify depression in MS patients.

 

Fatigue is one of MS’ most common and troublesome symptoms.^12,13 It typically mounts gradually during the day and after activity or heat exposure. Thus, fatigue early in the morning or manifesting as diminished motivation may point to a depressive disorder.

 

Cognitive deterioration. Clinically significant cognitive dysfunction occurs in 45% to 65% of MS patients.¹⁴ The disease can cause losses in short-term memory, attention, information processing, problem solving, multitasking, and language function.

 

Bedside cognitive function tests such as the Mini-Mental State Examination¹⁵ often are not sensitive enough to detect MS-related cognitive dysfunction. Be alert for changes in cognitive style when assessing for depressive disorders in these patients. Feelings of worthlessness and guilt or suicidal ideation are not normal MS symptoms and point to depression.

MS patients may experience pathological laughing and crying—also known as involuntary emotional expression disorder (IEED)—a neurologic phenomenon that causes uncontrollable laughing, crying, or anger in the absence of subjective emotional distress. IEED has been reported in approximately 10% of patients with MS (Box 2).^16-22

CASE CONTINUED: Learning to adjust

Since discontinuing paroxetine 5 years ago, Mrs. S has not experienced another depressive episode. However, she describes a history of mood changes associated with pressured speech, increased activity, irritability, and insomnia during cortisone treatment for idiopathic thrombocytopenic purpura 4 years earlier. These episodes were mild, and she did not seek psychiatric treatment.

Mrs. S’ mood episode does not seem to be a recurrence of major depressive disorder because she lacks persistent depressed mood and major depressive symptoms. Her diagnosis is best understood as an adjustment disorder to the progression of her illness and her daughter leaving home. Fatigue is her most debilitating MS symptom.

Medication options

Use a cautious approach to pharmacotherapy. MS patients may have diminished cognitive reserves and might be at increased risk of medication-related delirium.

Depression. Two randomized, controlled trials have confirmed antidepressants’ efficacy for treating depression in MS patients. The studies investigated the tricyclic antidepressant desipramine²³ and the selective serotonin reuptake inhibitor (SSRI) sertraline.²⁴

In a double-blind clinical trial, 28 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy or placebo and psychotherapy. Patients receiving desipramine showed significantly greater improvement than the placebo group, as measured by clinical judgment.

A 16-week study compared the efficacy of cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG), and sertraline in 63 MS patients with major depressive disorder. Results showed that CBT and sertraline were more effective in reducing depression than SEG.²⁴

SSRIs are a common first choice because of their ease of use and general tolerability among MS patients.²⁵ Recommended dosages include:

 

• citalopram, 20 to 40 mg/d
• fluoxetine, 20 to 40 mg/d
• fluvoxamine, 50 to 300 mg/d
• paroxetine, 20 to 50 mg/d
• sertraline, 50 to 200 mg/d.

There is no consensus that any one antidepressant is best for all MS patients, however. When selecting an antidepressant, consider side-effect profiles, potential for drug-drug interactions, and a history of response to a particular antidepressant. Highly sedating antidepressants such as mirtazapine could aggravate fatigue. Highly anticholinergic agents such as amitriptyline may impair cognitive function.

 

 

Fatigue. Amantadine is the mainstay pharmacologic treatment for fatigue in MS, but evidence for its efficacy is weak.²⁶ Clinical trials of psychostimulants generally have reported disappointing results. One randomized, double-blind trial found no significant differences in fatigue levels between patients receiving pemoline or placebo.²⁷

 

Some studies have reported reduced MS-related fatigue with modafinil,^28-30 but the only double-blind, placebo-controlled trial showed no significant difference between modafinil and placebo in patient fatigue levels.³¹ In this study, modafinil reduced physical fatigue only in patients with daytime somnolence.

 

Box 1

 

Other psychiatric disorders

Bipolar disorder occurs more frequently in MS patients than in the general population.³² Additionally, some patients with advanced MS might experience benign feelings of euphoria.³³ Euphoria can be differentiated from mania by assessing for mania’s other symptoms, such as erratic and disinhibited behavior, rapid speech, increased libido, decreased need for sleep, and excessive energy.

Antidepressants and corticosteroids could aggravate the course of bipolar disorder, and drug-illness interactions with lithium could make side effects such as tremor, diarrhea, and polyuria more difficult to tolerate. Mood stabilizing anticonvulsants such as valproate and carbamazepine are a useful alternative for treating the bipolar patient with comorbid MS. To avoid sedation, start with a low dose and increase gradually.

Box 2

 

Insomnia. Sedative hypnotics such as zopiclone can be used for short-term treatment of sleep disturbances. Carefully consider hypnotics’ possible negative effects on balance, coordination, and memory, however.

 

Psychotic disturbances are rare in MS but occur more frequently in MS patients than in the general population.³⁴ Use low doses of antipsychotics such as olanzapine, quetiapine, or risperidone in MS patients with psychosis. These atypical agents are associated with a lower risk of parkinsonian side effects than typical antipsychotics.

 

CASE CONTINUED: Coping mechanisms

Mrs. S has difficulty coping with her increasing symptom burden and functional limitations, but she says it is hard for her to ask for help. Her treatment plan includes recruiting support to help her deal with feelings of loss over her daughter’s move. We encourage her to reconnect with friends and family and use community supports for MS patients.

 

We discuss her treatment options, including biological treatments for fatigue, CBT, and behavioral activation therapy for her mood symptoms. She chooses a course of modafinil, 50 mg/d, and weekly CBT incorporating behavioral activation therapy to increase her activity level and target depressive symptoms and fatigue.

 

 

Psychosocial interventions

 

CBT is an effective treatment for depression in MS patients²⁴ and is preferred for most patients with mild depression. CBT focuses on improving coping through behavioral activation and cognitive restructuring.³⁵ CBT can incorporate teaching patients skills for managing MS-related problems such as fatigue, mild cognitive impairment, pain, stress, communication, sexual dysfunction, intimacy, and social difficulties secondary to MS.

Behavioral activation strategies focus on the relationship between activity and mood. They target a common pattern of avoidance and withdrawal from social, occupational, and physical demands that relieves MS patients’ anxiety in the short term but leads to problems associated with inactivity.³⁵ Behavioral activation strategies—including exercise—have a strong evidence base supporting their use alone to manage depression and as a component of CBT.³⁶

 

Active coping strategies. In early MS, patients often use avoidance and denial to cope with their disease. As symptoms become more intrusive, however, patients usually need to learn active coping strategies. These often begin with symptom management and evolve to include individually meaningful tasks such as reevaluating personal goals, values, and priorities.

 

Other psychotherapy modalities. In one study, patients randomized to an insight-oriented treatment group improved more than those in a placebo intervention based on discussing current events.³⁷ Although not formally assessed in the literature, psychoeducation can help the patient maintain a sense of control over his or her treatment. Interpersonal therapy can help patients deal with role transitions caused by their illness and subsequent disabilities, although its use in this population has not been studied.

 

Although the literature does not favor supportive psychotherapy for treating depression in MS patients,²⁴ this modality can help alleviate feelings of grief and loss that can emerge when MS symptoms worsen. Patients often appreciate having an opportunity to articulate their feelings and fears in a professional therapeutic relationship. MS patients often value validation and normalization of their emotional responses, and many therapists choose to integrate supportive strategies with CBT’s more “action oriented” elements.

 

Exercise is an effective treatment for fatigue in MS³⁸ and also helps combat loss of physical fitness. MS patients who use energy conservation strategies to manage fatigue can participate in suitably paced physical exercise. Aquatic exercise is a popular option because it often does not cause overheating.

 

CASE CONTINUED: Energy surge

 

At the second follow-up appointment, Mrs. S notes that her energy level is better early in the day but decreases by late afternoon. An additional dose of modafinil, 50 mg, is added at noon, which increases her overall energy level.

CBT helps Mrs. S to develop reasonable expectations of herself and others and addresses the possibility that she could try part-time work. Including exercise as behavioral activation also lessens her fatigue. Reconnecting with family and friends helps relieve feelings of isolation resulting from her daughter moving away.

Related resources

 

• National Multiple Sclerosis Society. www.nationalmssociety.org.
• The Goldman Consensus Group. The Goldman Consensus statement on depression in multiple sclerosis. Mult Scler 2005;11:328-37.
• Feinstein A. The clinical neuropsychiatry of multiple sclerosis. Cambridge, UK: Cambridge University Press; 2007.

Drug brand names

 

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Interferon beta-1a • Avonex, Rebif
• Interferon beta-1b • Betaseron
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Modafinil • Provigil
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Pemoline • Cylert
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Valproate • Depacon
• Zopiclone • Imovane, Zimovane

Disclosure

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

Mrs. S, age 50, has had relapsing-remitting multiple sclerosis (MS) for approximately 10 years. She describes her mood as “up and down” and is referred by her neurologist for psychiatric assessment of mood swings and possible depression. Fatigue limits her ability to work full-time, perform household duties, socialize with friends and family, and enjoy mental or physical exercise. In addition, her 18-year-old daughter—an important source of psychological support—is planning to leave home.

Mrs. S experienced depression 5 years ago during her divorce. She was prescribed paroxetine, 20 mg/d, and had a positive response. She took the medication for 6 months, then discontinued.

One-half of MS patients experience major depression in their lifetimes,¹ and the suicide rate is approximately doubled in MS patients compared with the general population.² Depression in MS patients often has an atypical presentation, with irritability and anger being as prominent as sadness.³ Not all emotional changes experienced by MS patients represent depressive disorders, however.

When evaluating MS patients who are struggling with depression, you can help them by diagnosing comorbid mood disorders, determining suicide risk, and providing psychological support as they cope with the impact of their illness.

MS disease course

MS is a disease of the brain and spinal cord, characterized by:

 

• inflammatory demyelination and gliosis
• neuronal and axonal loss
• a variety of presenting symptoms as different CNS regions are affected.

Focal areas of demyelination followed by a reactive gliosis cause white matter lesions in the brain, spinal cord, and optic nerve. Neurologic dysfunction can manifest as visual changes, spastic paresis, hypoesthesia and paresthesia, ataxia, and bowel and bladder dysfunction. MS presentation also can include optic neuritis and transverse myelitis. MS symptoms often are intensified by heat exposure.

After the initial episode, months or years may pass before additional neurologic symptoms appear. Based on its course, MS can be classified as:

 

• relapsing-remitting, when the disease does not progress between attacks
• secondary progressive, characterized by a gradually progressive course after an initial relapsing-remitting pattern
• primary progressive, when patients experience gradual progressive disability from symptom onset (Table 1).

Table 1

Clinical classification of multiple sclerosis (MS)

 

Type	Characteristics
Relapsing-remitting*	Symptoms appear during relapses, resolve during remissions, and do not progress between relapses
Secondary progressive	MS symptoms that previously followed a relapsing-remitting pattern steadily become more severe and progress without relapse
Primary progressive	Gradual progression from symptom onset, without relapses or remission
Clinically isolated syndrome	A single attack that may indicate MS has occurred—such as optic neuritis or transverse myelitis—but clinical requirements for the diagnosis have not been met
* Patients often progress from relapsing-remitting to secondary progressive MS

CASE CONTINUED: Progressing symptoms

Mrs. S has had multiple MS presentations, including optic neuritis, lower extremity weakness, balance problems, and urinary incontinence. Recently, her MS symptoms have gradually progressed even in the absence of attacks, and her diagnosis has been revised to secondary progressive MS.

During psychiatric evaluation, Mrs. S denies persistent changes in sleep or appetite. She describes fatigue that starts after physical exertion and increases as the day progresses. She denies feelings of worthlessness, helplessness, excessive guilt, and suicidal ideation and does not have a history of inappropriate anger or irritability.

Diagnosing depression in MS

Normal emotional adjustment to MS can include reactions to loss of function or changes in social or occupational roles. Further, MS patients—similar to non-MS patients—experience life changes and transitions not related to the illness, such as divorce or a grown child moving away. Emotional responses to life stressors often are self-limited but may warrant an adjustment disorder diagnosis if they are associated with excessive distress or substantial impairment in social, occupational, or academic functioning (Table 2).⁴

Table 2

Questions to consider when assessing MS patients for depression

 

Ask yourself	Reason
Are symptoms part of normal emotional changes?	Not all mood changes are pathologic or meet criteria for major depression
Is this an adjustment disorder?	Mood symptoms can be caused by a major stressor such as a recent diagnosis or personal loss
Is fatigue secondary to MS or depression?	MS typically causes fatigue after physical activity and heat exposure; fatigue early in the day points to depression
Are cognitive deficits related to MS or depression?	Negative thoughts point to depression whereas cognitive deficits may be caused by depression, MS, or both
Is this an atypical presentation?	MS patients may present with anger or irritability
Is this a pseudobulbar problem?	Patients with IEED might describe more concern about affect dysregulation than mood swings
MS: multiple sclerosis; IEED: involuntary emotional expression disorder

Female MS patients and those who report high stress or a family history of affective disorder may be more likely to develop clinical depression.⁵ Several studies have reported correlations between structural brain abnormalities and depression in MS. Feinstein et al

 

⁶ reported that extensive hyper intense lesion volume in the left medial inferior prefrontal region with atrophy affecting the dominant anterior temporal lobe was associated with major depression. However, a depression diagnosis in MS patients remains a clinical one that does not require brain imaging studies.

Lack of interest or enjoyment as a symptom of depression can be difficult to identify because MS can diminish enjoyment of some activities. Although patients with MS may need to change their activity patterns to accommodate their illness, the lack of enjoyment in all—or almost all—activities remains a valid indicator of depressive disorder.

MS treatment includes the use of disease-modifying medications such as interferon beta-1b and interferon beta-1a. Several years ago researchers were concerned that interferon beta might cause depression in MS patients based on reports of a suicide and attempted suicide during an early trial of interferon beta-1b in relapsing-remitting MS.⁷ Subsequent studies did not substantiate this concern, however (Box 1).^8,9

 

Overlapping symptoms such as fatigue and cognitive deterioration could complicate the diagnosis. Look for changing patterns of these symptoms and other signs of depression. Rating scales that do not emphasize fatigue and cognitive impairment—such as the Beck Depression Inventory¹⁰ and the Center for Epidemiologic Studies Depression Rating Scale¹¹—can help identify depression in MS patients.

 

Fatigue is one of MS’ most common and troublesome symptoms.^12,13 It typically mounts gradually during the day and after activity or heat exposure. Thus, fatigue early in the morning or manifesting as diminished motivation may point to a depressive disorder.

 

Cognitive deterioration. Clinically significant cognitive dysfunction occurs in 45% to 65% of MS patients.¹⁴ The disease can cause losses in short-term memory, attention, information processing, problem solving, multitasking, and language function.

 

Bedside cognitive function tests such as the Mini-Mental State Examination¹⁵ often are not sensitive enough to detect MS-related cognitive dysfunction. Be alert for changes in cognitive style when assessing for depressive disorders in these patients. Feelings of worthlessness and guilt or suicidal ideation are not normal MS symptoms and point to depression.

MS patients may experience pathological laughing and crying—also known as involuntary emotional expression disorder (IEED)—a neurologic phenomenon that causes uncontrollable laughing, crying, or anger in the absence of subjective emotional distress. IEED has been reported in approximately 10% of patients with MS (Box 2).^16-22

CASE CONTINUED: Learning to adjust

Since discontinuing paroxetine 5 years ago, Mrs. S has not experienced another depressive episode. However, she describes a history of mood changes associated with pressured speech, increased activity, irritability, and insomnia during cortisone treatment for idiopathic thrombocytopenic purpura 4 years earlier. These episodes were mild, and she did not seek psychiatric treatment.

Mrs. S’ mood episode does not seem to be a recurrence of major depressive disorder because she lacks persistent depressed mood and major depressive symptoms. Her diagnosis is best understood as an adjustment disorder to the progression of her illness and her daughter leaving home. Fatigue is her most debilitating MS symptom.

Medication options

Use a cautious approach to pharmacotherapy. MS patients may have diminished cognitive reserves and might be at increased risk of medication-related delirium.

Depression. Two randomized, controlled trials have confirmed antidepressants’ efficacy for treating depression in MS patients. The studies investigated the tricyclic antidepressant desipramine²³ and the selective serotonin reuptake inhibitor (SSRI) sertraline.²⁴

In a double-blind clinical trial, 28 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy or placebo and psychotherapy. Patients receiving desipramine showed significantly greater improvement than the placebo group, as measured by clinical judgment.

A 16-week study compared the efficacy of cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG), and sertraline in 63 MS patients with major depressive disorder. Results showed that CBT and sertraline were more effective in reducing depression than SEG.²⁴

SSRIs are a common first choice because of their ease of use and general tolerability among MS patients.²⁵ Recommended dosages include:

 

• citalopram, 20 to 40 mg/d
• fluoxetine, 20 to 40 mg/d
• fluvoxamine, 50 to 300 mg/d
• paroxetine, 20 to 50 mg/d
• sertraline, 50 to 200 mg/d.

There is no consensus that any one antidepressant is best for all MS patients, however. When selecting an antidepressant, consider side-effect profiles, potential for drug-drug interactions, and a history of response to a particular antidepressant. Highly sedating antidepressants such as mirtazapine could aggravate fatigue. Highly anticholinergic agents such as amitriptyline may impair cognitive function.

 

 

Fatigue. Amantadine is the mainstay pharmacologic treatment for fatigue in MS, but evidence for its efficacy is weak.²⁶ Clinical trials of psychostimulants generally have reported disappointing results. One randomized, double-blind trial found no significant differences in fatigue levels between patients receiving pemoline or placebo.²⁷

 

Some studies have reported reduced MS-related fatigue with modafinil,^28-30 but the only double-blind, placebo-controlled trial showed no significant difference between modafinil and placebo in patient fatigue levels.³¹ In this study, modafinil reduced physical fatigue only in patients with daytime somnolence.

 

Box 1

 

Other psychiatric disorders

Bipolar disorder occurs more frequently in MS patients than in the general population.³² Additionally, some patients with advanced MS might experience benign feelings of euphoria.³³ Euphoria can be differentiated from mania by assessing for mania’s other symptoms, such as erratic and disinhibited behavior, rapid speech, increased libido, decreased need for sleep, and excessive energy.

Antidepressants and corticosteroids could aggravate the course of bipolar disorder, and drug-illness interactions with lithium could make side effects such as tremor, diarrhea, and polyuria more difficult to tolerate. Mood stabilizing anticonvulsants such as valproate and carbamazepine are a useful alternative for treating the bipolar patient with comorbid MS. To avoid sedation, start with a low dose and increase gradually.

Box 2

 

Insomnia. Sedative hypnotics such as zopiclone can be used for short-term treatment of sleep disturbances. Carefully consider hypnotics’ possible negative effects on balance, coordination, and memory, however.

 

Psychotic disturbances are rare in MS but occur more frequently in MS patients than in the general population.³⁴ Use low doses of antipsychotics such as olanzapine, quetiapine, or risperidone in MS patients with psychosis. These atypical agents are associated with a lower risk of parkinsonian side effects than typical antipsychotics.

 

CASE CONTINUED: Coping mechanisms

Mrs. S has difficulty coping with her increasing symptom burden and functional limitations, but she says it is hard for her to ask for help. Her treatment plan includes recruiting support to help her deal with feelings of loss over her daughter’s move. We encourage her to reconnect with friends and family and use community supports for MS patients.

 

We discuss her treatment options, including biological treatments for fatigue, CBT, and behavioral activation therapy for her mood symptoms. She chooses a course of modafinil, 50 mg/d, and weekly CBT incorporating behavioral activation therapy to increase her activity level and target depressive symptoms and fatigue.

 

 

Psychosocial interventions

 

CBT is an effective treatment for depression in MS patients²⁴ and is preferred for most patients with mild depression. CBT focuses on improving coping through behavioral activation and cognitive restructuring.³⁵ CBT can incorporate teaching patients skills for managing MS-related problems such as fatigue, mild cognitive impairment, pain, stress, communication, sexual dysfunction, intimacy, and social difficulties secondary to MS.

Behavioral activation strategies focus on the relationship between activity and mood. They target a common pattern of avoidance and withdrawal from social, occupational, and physical demands that relieves MS patients’ anxiety in the short term but leads to problems associated with inactivity.³⁵ Behavioral activation strategies—including exercise—have a strong evidence base supporting their use alone to manage depression and as a component of CBT.³⁶

 

Active coping strategies. In early MS, patients often use avoidance and denial to cope with their disease. As symptoms become more intrusive, however, patients usually need to learn active coping strategies. These often begin with symptom management and evolve to include individually meaningful tasks such as reevaluating personal goals, values, and priorities.

 

Other psychotherapy modalities. In one study, patients randomized to an insight-oriented treatment group improved more than those in a placebo intervention based on discussing current events.³⁷ Although not formally assessed in the literature, psychoeducation can help the patient maintain a sense of control over his or her treatment. Interpersonal therapy can help patients deal with role transitions caused by their illness and subsequent disabilities, although its use in this population has not been studied.

 

Although the literature does not favor supportive psychotherapy for treating depression in MS patients,²⁴ this modality can help alleviate feelings of grief and loss that can emerge when MS symptoms worsen. Patients often appreciate having an opportunity to articulate their feelings and fears in a professional therapeutic relationship. MS patients often value validation and normalization of their emotional responses, and many therapists choose to integrate supportive strategies with CBT’s more “action oriented” elements.

 

Exercise is an effective treatment for fatigue in MS³⁸ and also helps combat loss of physical fitness. MS patients who use energy conservation strategies to manage fatigue can participate in suitably paced physical exercise. Aquatic exercise is a popular option because it often does not cause overheating.

 

CASE CONTINUED: Energy surge

 

At the second follow-up appointment, Mrs. S notes that her energy level is better early in the day but decreases by late afternoon. An additional dose of modafinil, 50 mg, is added at noon, which increases her overall energy level.

CBT helps Mrs. S to develop reasonable expectations of herself and others and addresses the possibility that she could try part-time work. Including exercise as behavioral activation also lessens her fatigue. Reconnecting with family and friends helps relieve feelings of isolation resulting from her daughter moving away.

Related resources

 

• National Multiple Sclerosis Society. www.nationalmssociety.org.
• The Goldman Consensus Group. The Goldman Consensus statement on depression in multiple sclerosis. Mult Scler 2005;11:328-37.
• Feinstein A. The clinical neuropsychiatry of multiple sclerosis. Cambridge, UK: Cambridge University Press; 2007.

Drug brand names

 

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Interferon beta-1a • Avonex, Rebif
• Interferon beta-1b • Betaseron
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Modafinil • Provigil
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Pemoline • Cylert
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Valproate • Depacon
• Zopiclone • Imovane, Zimovane

Disclosure

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

Mrs. S, age 50, has had relapsing-remitting multiple sclerosis (MS) for approximately 10 years. She describes her mood as “up and down” and is referred by her neurologist for psychiatric assessment of mood swings and possible depression. Fatigue limits her ability to work full-time, perform household duties, socialize with friends and family, and enjoy mental or physical exercise. In addition, her 18-year-old daughter—an important source of psychological support—is planning to leave home.

Mrs. S experienced depression 5 years ago during her divorce. She was prescribed paroxetine, 20 mg/d, and had a positive response. She took the medication for 6 months, then discontinued.

One-half of MS patients experience major depression in their lifetimes,¹ and the suicide rate is approximately doubled in MS patients compared with the general population.² Depression in MS patients often has an atypical presentation, with irritability and anger being as prominent as sadness.³ Not all emotional changes experienced by MS patients represent depressive disorders, however.

When evaluating MS patients who are struggling with depression, you can help them by diagnosing comorbid mood disorders, determining suicide risk, and providing psychological support as they cope with the impact of their illness.

MS disease course

MS is a disease of the brain and spinal cord, characterized by:

 

• inflammatory demyelination and gliosis
• neuronal and axonal loss
• a variety of presenting symptoms as different CNS regions are affected.

Focal areas of demyelination followed by a reactive gliosis cause white matter lesions in the brain, spinal cord, and optic nerve. Neurologic dysfunction can manifest as visual changes, spastic paresis, hypoesthesia and paresthesia, ataxia, and bowel and bladder dysfunction. MS presentation also can include optic neuritis and transverse myelitis. MS symptoms often are intensified by heat exposure.

After the initial episode, months or years may pass before additional neurologic symptoms appear. Based on its course, MS can be classified as:

 

• relapsing-remitting, when the disease does not progress between attacks
• secondary progressive, characterized by a gradually progressive course after an initial relapsing-remitting pattern
• primary progressive, when patients experience gradual progressive disability from symptom onset (Table 1).

Table 1

Clinical classification of multiple sclerosis (MS)

 

Type	Characteristics
Relapsing-remitting*	Symptoms appear during relapses, resolve during remissions, and do not progress between relapses
Secondary progressive	MS symptoms that previously followed a relapsing-remitting pattern steadily become more severe and progress without relapse
Primary progressive	Gradual progression from symptom onset, without relapses or remission
Clinically isolated syndrome	A single attack that may indicate MS has occurred—such as optic neuritis or transverse myelitis—but clinical requirements for the diagnosis have not been met
* Patients often progress from relapsing-remitting to secondary progressive MS

CASE CONTINUED: Progressing symptoms

Mrs. S has had multiple MS presentations, including optic neuritis, lower extremity weakness, balance problems, and urinary incontinence. Recently, her MS symptoms have gradually progressed even in the absence of attacks, and her diagnosis has been revised to secondary progressive MS.

During psychiatric evaluation, Mrs. S denies persistent changes in sleep or appetite. She describes fatigue that starts after physical exertion and increases as the day progresses. She denies feelings of worthlessness, helplessness, excessive guilt, and suicidal ideation and does not have a history of inappropriate anger or irritability.

Diagnosing depression in MS

Normal emotional adjustment to MS can include reactions to loss of function or changes in social or occupational roles. Further, MS patients—similar to non-MS patients—experience life changes and transitions not related to the illness, such as divorce or a grown child moving away. Emotional responses to life stressors often are self-limited but may warrant an adjustment disorder diagnosis if they are associated with excessive distress or substantial impairment in social, occupational, or academic functioning (Table 2).⁴

Table 2

Questions to consider when assessing MS patients for depression

 

Ask yourself	Reason
Are symptoms part of normal emotional changes?	Not all mood changes are pathologic or meet criteria for major depression
Is this an adjustment disorder?	Mood symptoms can be caused by a major stressor such as a recent diagnosis or personal loss
Is fatigue secondary to MS or depression?	MS typically causes fatigue after physical activity and heat exposure; fatigue early in the day points to depression
Are cognitive deficits related to MS or depression?	Negative thoughts point to depression whereas cognitive deficits may be caused by depression, MS, or both
Is this an atypical presentation?	MS patients may present with anger or irritability
Is this a pseudobulbar problem?	Patients with IEED might describe more concern about affect dysregulation than mood swings
MS: multiple sclerosis; IEED: involuntary emotional expression disorder

Female MS patients and those who report high stress or a family history of affective disorder may be more likely to develop clinical depression.⁵ Several studies have reported correlations between structural brain abnormalities and depression in MS. Feinstein et al

 

⁶ reported that extensive hyper intense lesion volume in the left medial inferior prefrontal region with atrophy affecting the dominant anterior temporal lobe was associated with major depression. However, a depression diagnosis in MS patients remains a clinical one that does not require brain imaging studies.

Lack of interest or enjoyment as a symptom of depression can be difficult to identify because MS can diminish enjoyment of some activities. Although patients with MS may need to change their activity patterns to accommodate their illness, the lack of enjoyment in all—or almost all—activities remains a valid indicator of depressive disorder.

MS treatment includes the use of disease-modifying medications such as interferon beta-1b and interferon beta-1a. Several years ago researchers were concerned that interferon beta might cause depression in MS patients based on reports of a suicide and attempted suicide during an early trial of interferon beta-1b in relapsing-remitting MS.⁷ Subsequent studies did not substantiate this concern, however (Box 1).^8,9

 

Overlapping symptoms such as fatigue and cognitive deterioration could complicate the diagnosis. Look for changing patterns of these symptoms and other signs of depression. Rating scales that do not emphasize fatigue and cognitive impairment—such as the Beck Depression Inventory¹⁰ and the Center for Epidemiologic Studies Depression Rating Scale¹¹—can help identify depression in MS patients.

 

Fatigue is one of MS’ most common and troublesome symptoms.^12,13 It typically mounts gradually during the day and after activity or heat exposure. Thus, fatigue early in the morning or manifesting as diminished motivation may point to a depressive disorder.

 

Cognitive deterioration. Clinically significant cognitive dysfunction occurs in 45% to 65% of MS patients.¹⁴ The disease can cause losses in short-term memory, attention, information processing, problem solving, multitasking, and language function.

 

Bedside cognitive function tests such as the Mini-Mental State Examination¹⁵ often are not sensitive enough to detect MS-related cognitive dysfunction. Be alert for changes in cognitive style when assessing for depressive disorders in these patients. Feelings of worthlessness and guilt or suicidal ideation are not normal MS symptoms and point to depression.

MS patients may experience pathological laughing and crying—also known as involuntary emotional expression disorder (IEED)—a neurologic phenomenon that causes uncontrollable laughing, crying, or anger in the absence of subjective emotional distress. IEED has been reported in approximately 10% of patients with MS (Box 2).^16-22

CASE CONTINUED: Learning to adjust

Since discontinuing paroxetine 5 years ago, Mrs. S has not experienced another depressive episode. However, she describes a history of mood changes associated with pressured speech, increased activity, irritability, and insomnia during cortisone treatment for idiopathic thrombocytopenic purpura 4 years earlier. These episodes were mild, and she did not seek psychiatric treatment.

Mrs. S’ mood episode does not seem to be a recurrence of major depressive disorder because she lacks persistent depressed mood and major depressive symptoms. Her diagnosis is best understood as an adjustment disorder to the progression of her illness and her daughter leaving home. Fatigue is her most debilitating MS symptom.

Medication options

Use a cautious approach to pharmacotherapy. MS patients may have diminished cognitive reserves and might be at increased risk of medication-related delirium.

Depression. Two randomized, controlled trials have confirmed antidepressants’ efficacy for treating depression in MS patients. The studies investigated the tricyclic antidepressant desipramine²³ and the selective serotonin reuptake inhibitor (SSRI) sertraline.²⁴

In a double-blind clinical trial, 28 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy or placebo and psychotherapy. Patients receiving desipramine showed significantly greater improvement than the placebo group, as measured by clinical judgment.

A 16-week study compared the efficacy of cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG), and sertraline in 63 MS patients with major depressive disorder. Results showed that CBT and sertraline were more effective in reducing depression than SEG.²⁴

SSRIs are a common first choice because of their ease of use and general tolerability among MS patients.²⁵ Recommended dosages include:

 

• citalopram, 20 to 40 mg/d
• fluoxetine, 20 to 40 mg/d
• fluvoxamine, 50 to 300 mg/d
• paroxetine, 20 to 50 mg/d
• sertraline, 50 to 200 mg/d.

There is no consensus that any one antidepressant is best for all MS patients, however. When selecting an antidepressant, consider side-effect profiles, potential for drug-drug interactions, and a history of response to a particular antidepressant. Highly sedating antidepressants such as mirtazapine could aggravate fatigue. Highly anticholinergic agents such as amitriptyline may impair cognitive function.

 

 

Fatigue. Amantadine is the mainstay pharmacologic treatment for fatigue in MS, but evidence for its efficacy is weak.²⁶ Clinical trials of psychostimulants generally have reported disappointing results. One randomized, double-blind trial found no significant differences in fatigue levels between patients receiving pemoline or placebo.²⁷

 

Some studies have reported reduced MS-related fatigue with modafinil,^28-30 but the only double-blind, placebo-controlled trial showed no significant difference between modafinil and placebo in patient fatigue levels.³¹ In this study, modafinil reduced physical fatigue only in patients with daytime somnolence.

 

Box 1

 

Other psychiatric disorders

Bipolar disorder occurs more frequently in MS patients than in the general population.³² Additionally, some patients with advanced MS might experience benign feelings of euphoria.³³ Euphoria can be differentiated from mania by assessing for mania’s other symptoms, such as erratic and disinhibited behavior, rapid speech, increased libido, decreased need for sleep, and excessive energy.

Antidepressants and corticosteroids could aggravate the course of bipolar disorder, and drug-illness interactions with lithium could make side effects such as tremor, diarrhea, and polyuria more difficult to tolerate. Mood stabilizing anticonvulsants such as valproate and carbamazepine are a useful alternative for treating the bipolar patient with comorbid MS. To avoid sedation, start with a low dose and increase gradually.

Box 2

 

Insomnia. Sedative hypnotics such as zopiclone can be used for short-term treatment of sleep disturbances. Carefully consider hypnotics’ possible negative effects on balance, coordination, and memory, however.

 

Psychotic disturbances are rare in MS but occur more frequently in MS patients than in the general population.³⁴ Use low doses of antipsychotics such as olanzapine, quetiapine, or risperidone in MS patients with psychosis. These atypical agents are associated with a lower risk of parkinsonian side effects than typical antipsychotics.

 

CASE CONTINUED: Coping mechanisms

Mrs. S has difficulty coping with her increasing symptom burden and functional limitations, but she says it is hard for her to ask for help. Her treatment plan includes recruiting support to help her deal with feelings of loss over her daughter’s move. We encourage her to reconnect with friends and family and use community supports for MS patients.

 

We discuss her treatment options, including biological treatments for fatigue, CBT, and behavioral activation therapy for her mood symptoms. She chooses a course of modafinil, 50 mg/d, and weekly CBT incorporating behavioral activation therapy to increase her activity level and target depressive symptoms and fatigue.

 

 

Psychosocial interventions

 

CBT is an effective treatment for depression in MS patients²⁴ and is preferred for most patients with mild depression. CBT focuses on improving coping through behavioral activation and cognitive restructuring.³⁵ CBT can incorporate teaching patients skills for managing MS-related problems such as fatigue, mild cognitive impairment, pain, stress, communication, sexual dysfunction, intimacy, and social difficulties secondary to MS.

Behavioral activation strategies focus on the relationship between activity and mood. They target a common pattern of avoidance and withdrawal from social, occupational, and physical demands that relieves MS patients’ anxiety in the short term but leads to problems associated with inactivity.³⁵ Behavioral activation strategies—including exercise—have a strong evidence base supporting their use alone to manage depression and as a component of CBT.³⁶

 

Active coping strategies. In early MS, patients often use avoidance and denial to cope with their disease. As symptoms become more intrusive, however, patients usually need to learn active coping strategies. These often begin with symptom management and evolve to include individually meaningful tasks such as reevaluating personal goals, values, and priorities.

 

Other psychotherapy modalities. In one study, patients randomized to an insight-oriented treatment group improved more than those in a placebo intervention based on discussing current events.³⁷ Although not formally assessed in the literature, psychoeducation can help the patient maintain a sense of control over his or her treatment. Interpersonal therapy can help patients deal with role transitions caused by their illness and subsequent disabilities, although its use in this population has not been studied.

 

Although the literature does not favor supportive psychotherapy for treating depression in MS patients,²⁴ this modality can help alleviate feelings of grief and loss that can emerge when MS symptoms worsen. Patients often appreciate having an opportunity to articulate their feelings and fears in a professional therapeutic relationship. MS patients often value validation and normalization of their emotional responses, and many therapists choose to integrate supportive strategies with CBT’s more “action oriented” elements.

 

Exercise is an effective treatment for fatigue in MS³⁸ and also helps combat loss of physical fitness. MS patients who use energy conservation strategies to manage fatigue can participate in suitably paced physical exercise. Aquatic exercise is a popular option because it often does not cause overheating.

 

CASE CONTINUED: Energy surge

 

At the second follow-up appointment, Mrs. S notes that her energy level is better early in the day but decreases by late afternoon. An additional dose of modafinil, 50 mg, is added at noon, which increases her overall energy level.

CBT helps Mrs. S to develop reasonable expectations of herself and others and addresses the possibility that she could try part-time work. Including exercise as behavioral activation also lessens her fatigue. Reconnecting with family and friends helps relieve feelings of isolation resulting from her daughter moving away.

Related resources

 

• National Multiple Sclerosis Society. www.nationalmssociety.org.
• The Goldman Consensus Group. The Goldman Consensus statement on depression in multiple sclerosis. Mult Scler 2005;11:328-37.
• Feinstein A. The clinical neuropsychiatry of multiple sclerosis. Cambridge, UK: Cambridge University Press; 2007.

Drug brand names

 

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Interferon beta-1a • Avonex, Rebif
• Interferon beta-1b • Betaseron
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Modafinil • Provigil
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Pemoline • Cylert
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Valproate • Depacon
• Zopiclone • Imovane, Zimovane

Disclosure

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