Current Psychiatry

More than 50% of psychiatrists have experienced the death of a patient by suicide.¹ For many of us, suicide represents the most feared outcome of a patient’s mental illness and makes managing suicide risk critical to everyday practice.

Unfortunately, we have little ability to predict suicide. Research into risk factors and the use of suicide rating scales have produced no consistently definitive methods to determine who will and who will not attempt or complete suicide.² The purpose of suicide assessment, then, is not to predict suicide but to help us understand the sources of a patient’s suicidality and develop an informed intervention.

This article describes a practical, commonly accepted approach to suicide risk assessment and intervention, based on the B-SAFE model (Basic Suicide Assessment Five-step Evaluation) proposed by Jacobs et al (Figure).³ Using this method to assess suicide risk can help you answer questions such as:

• Which factors are most important to consider when evaluating suicide risk in my patient?
• What questions should I ask my patient to find out if he or she is suicidal?
• How do I know if a patient is at risk for suicide?
• What emergent interventions are called for when managing the acutely suicidal patient?
• How should I document a suicide risk assessment?

Figure Basic Suicide Assessment Five-step Evaluation (B-SAFE)

Source: Created from information in references 2,11

Why ask about suicide?

No single risk factor or combination of risk factors can predict or preclude suicide. Even so, attempting to evaluate an individual’s risk by asking about suicidal thinking, reviewing risk factors, or using clinical rating scales helps you determine the next appropriate action (discharge, medication, psychiatric referral, consultation, or hospitalization).

While talking to patients and evaluating their risk for suicide, you may begin to understand their suffering—described as the most common denominator in suicide² and perhaps the most important clue to heightened suicide risk. Such an exploration allows you to identify potential:

• risk factors that can be modified
• preventative factors to promote.

Don’t be afraid to ask. Asking about suicidal thoughts is necessary—but not enough—to understand an individual’s potential for suicide. Never be afraid to ask patients about suicide, believing that doing so will “put ideas into their heads.” By the same token, a patient who denies thoughts or plans for suicide may still be at risk.

Identifying at-risk patients is much more difficult than just asking if they are considering suicide. Opening a concerned dialogue can provide a sense of relief to the patient while allowing you to explore:

• the extent and seriousness of the suicidal thoughts
• associated risk factors or conditions, such as depression.

Stepwise risk assessment

The first 3 steps of Jacobs’ B-SAFE model focus on identifying predisposing and protective factors for suicide.³ For an in-depth discussion, consult the American Psychiatric Association practice guideline for the assessment and treatment of patients with suicidal behaviors⁴ (available at http://www.psych.org/psych_pract/treatg/pg/suicidalbehavior_05-15-06.pdf).

STEP 1: Risk factors. Use the patient interview, medical records, and collateral information to uncover potential suicide risk factors (Table 1).²

Psychopathology. Focus on depression, bipolar disorder, schizophrenia, substance abuse, and personality disorders, which are strongly associated with suicide. These disorders are considered modifiable risk factors—diagnosis and appropriate treatment can diminish suicide risk.

Suicidality has been associated with early depression or bipolar disorder, often before patients receive a diagnosis or effective treatment. Recovery and immediate post-discharge periods also are thought to be times of heightened suicide risk.

Psychosocial variables. Demographic and psychosocial variables may influence suicide risk estimation. A retrospective study of 100 patients who attempted suicide suggests that the most predictive factors for suicide are:

• living alone
• being aged 17 to 35 (although in other studies, more advanced age also has been linked to increased suicide risk³)
• complaints of severe hopelessness, anhedonia, and insomnia.⁵

Physical illness may potentiate suicide risk. Medical illnesses that produce great pain, disfigurement, limited function, or fear of dependence may reduce a person’s will to live and increase suicide risk.⁶ Epilepsy has been associated with a 4- to 5-fold increase in suicide risk⁷ and is the only medical diagnosis to carry a documented increase in suicide among children and adolescents.⁸ Often these medical disorders coexist with psychiatric disorders, complicating the task of determining independent risk.

Severity of attempts or self-mutilation. When evaluating self-injurious or suicidal behavior in the emergency setting, consider the severity of the attempt as part of overall suicide assessment. Self-injurious behavior (cutting or burning) or impulsive suicide attempts (planned for <3 hours, committed in the presence others, or where discovery is very probable) appear to carry less severity or intent to die than do carefully planned and/or hidden suicide attempts.⁹ However, consider at high risk for suicide any patient with self-mutilating or suicidal behavior who expresses persistent intent to die; acute stabilization on an in-patient unit may be necessary.

STEP 2: ‘Protective’ factors. Discover and discuss internal and external factors that might help prevent the individual with suicidal thoughts from converting those thoughts into action (Table 2).² When discussing these potentially protective effects, emphasize the patient’s:

• resilience during past personal crises
• family responsibilities
• religious or spiritual beliefs.

‘No-harm contracts.’ Suicide (or “no-harm”) contracts with patients might help open communication about factors that promote or mitigate suicide risk. Such contacts do not prevent suicide or lessen medicolegal risk in the event of a patient suicide, however.¹⁰

STEP 3: Suicide plans. Ask about suicide thoughts, plans, and behaviors (Table 3).¹¹ Probe gently to allow the individual to discuss his or her feelings and to explore the next appropriate avenue of care.

In my experience, patients who reveal passive suicidal ideation (such as, “I sometimes wish I would just die in my sleep”) and strong deterrents to acting on thoughts of suicide (such as, “My children need me,” or “It’s against my religion”) should continue outpatient treatment. Those without deterrents or who discuss active and imminent thoughts and recent actions—writing suicide notes, buying a weapon, stockpiling pills—require emergent evaluation for psychiatric admission. Ask about thoughts of self-injury or mutilation (such as cutting or burning), as well as homicidal ideation.

Recognizing that patients with suicidal thoughts are almost always ambivalent about suicide to some extent—conflicted by simultaneous desires to live and to die—gives you the opportunity to intervene by allying with the part of the patient that wants to live. Creating a therapeutic connection also will help you determine the level of intervention required.

STEP 4: Intervention. Understanding why a patient feels suicidal—gathered in Steps 1 to 3—can help you choose the appropriate intervention. Among the 5 steps, Step 4 relies most heavily on clinical judgment:

• Is the suicidality acute or chronic?
• How great is the risk for suicide?
• To keep the patient safe, how urgent is the required intervention?

Acute risk. Suicidality related to Axis I psychiatric disorders tends to be acute, with prominent pain, anguish, and a desire to escape. Patients may describe a driven quality to the suicidality, which commands a treatment plan that maintains patient safety until suicidal feelings remit.

Hospitalization is often needed, plus focused treatments such as medication, psychotherapy, or electroconvulsive therapy. Intensive outpatient follow-up or partial hospitalization programs might be considered for patients:

• with whom you have a strong therapeutic alliance
• who have sturdy psychosocial support
• whose precipitating factors for suicidality have resolved.

Chronic risk. Suicide risk tends to be more chronic and has an impulsive quality for patients with suicidality related to personality disorders and environmental factors. Personality disordered patients may report feelings of anger, rage, or vengeance connected with their suicidal thoughts.

Hospitalization might become necessary, although multiple hospitalizations can be counter-therapeutic. Attempting in therapy to teach the patient to cope with suicidal thoughts and feelings might be a more effective intervention.

Malingering. Use your best judgment when patients make suicide threats that could represent malingering to achieve hospitalization.

Step 5: Documentation. Document your assessment of the suicidal patient and decision making to:

• clarify the treatment plan
• communicate to other caregivers
• manage medicolegal risk.

Include a brief summary (Box) that is timely, legible, and communicates the estimated degree of risk, known data, diagnosis, and planned interventions such as medications, tests, consultations, and follow-up reassessments.

Box

Table 1

Factors associated with potential for increased suicide risk

Table 2

Potentially protective factors against suicide

Table 3

Evaluating suicide risk: Questions to ask patients

Interventions for suicidal patients

Physical protection. Take decisive action when you determine that suicide risk is elevated and imminent. Pursue urgent psychiatric hospitalization, with or without patient consent, in accordance with local probate and involuntary commitment statutes.

The logistics of protective action can be challenging; transportation is often required, and the patient is not always cooperative with admission. Table 4 lists measures and precautions that can help keep the suicidal patient safe.

Disease-specific interventions. Because suicidal ideation is often symptomatic of a primary psychiatric disorder, rapidly identifying major depression, bipolar disorder, or a psychotic illness is crucial to reducing suicidal thoughts and behaviors. Prescribe appropriate antidepressants, mood stabilizers, and antipsychotics at adequate doses and for sufficient duration.

Be vigilant for distressing symptoms that may be elevating the patient’s suicide risk, such as anxiety, panic, agitation, insomnia, or pain. Pharmacotherapies—such as anxiolytics, sedative-hypnotics, antipsychotics, or analgesics—may rapidly reduce suffering.

Impulsivity associated with substance use disorders—particularly during intoxication and withdrawal syndromes—requires aggressive attempts by the treatment team to engage the patient in detoxification and rehabilitation.

Direct antisuicide therapy. Clozapine carries an FDA-approved indication for preventing suicide in patients with schizophrenia or schizoaffective disorder. The mechanism by which clozapine helps prevent suicide is not known, but its anti-suicidal effects appear to be independent of its antipsychotic effects.¹²

Lithium has been reported to reduce risk of suicide and suicide attempts in patients with bipolar disorder, perhaps by as much as 80%.¹³ Such benefit has not been observed with other mood stabilizers, suggesting that lithium confers protective effects against suicide beyond its mood-stabilizing effects. Suicide risk is known to increase after lithium is discontinued.¹⁴

Lithium’s antisuicidal effects may arise from its ability to enhance serotonin. This theory, although unproven, is consistent with observations associating central serotonergic deficiency with suicidal and aggressive behaviors.

Psychosocial measures. Address psychosocial variables that may increase suicide risk (Table 1). Recruit and involve the patient’s support system, augmented with a close follow-up plan. Case management to explore housing and job opportunities can help. Work with the patient’s family or others to remove guns from the patient’s access. Individual, marital, and family therapies can reduce conflicts and strengthen coping skills.

Table 4

Safety measures to protect the suicidal patient

Related resources

• National Suicide Prevention Lifeline, sponsored by the Substance Abuse & Mental Health Services Administration: 1-800-SUICIDE or 1-800-273-TALK (8255); www.suicidepreventionlifeline.org.
• American Foundation for Suicide Prevention (AFSP) 1-888-333-AFSP; www.afsp.org.
• Simon RI, Hales RE. Textbook of suicide assessment and management. Washington, DC: American Psychiatric Publishing; 2006.

Drug brand names

• Clozapine • Clozaril
• Lithium • Eskalith, Lithobid, others

Disclosure

Dr. Muzina has received grants from or served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Novartis Pharmaceuticals Corp., Pfizer, and Repligen.

More than 50% of psychiatrists have experienced the death of a patient by suicide.¹ For many of us, suicide represents the most feared outcome of a patient’s mental illness and makes managing suicide risk critical to everyday practice.

Unfortunately, we have little ability to predict suicide. Research into risk factors and the use of suicide rating scales have produced no consistently definitive methods to determine who will and who will not attempt or complete suicide.² The purpose of suicide assessment, then, is not to predict suicide but to help us understand the sources of a patient’s suicidality and develop an informed intervention.

This article describes a practical, commonly accepted approach to suicide risk assessment and intervention, based on the B-SAFE model (Basic Suicide Assessment Five-step Evaluation) proposed by Jacobs et al (Figure).³ Using this method to assess suicide risk can help you answer questions such as:

• Which factors are most important to consider when evaluating suicide risk in my patient?
• What questions should I ask my patient to find out if he or she is suicidal?
• How do I know if a patient is at risk for suicide?
• What emergent interventions are called for when managing the acutely suicidal patient?
• How should I document a suicide risk assessment?

Figure Basic Suicide Assessment Five-step Evaluation (B-SAFE)

Source: Created from information in references 2,11

Why ask about suicide?

No single risk factor or combination of risk factors can predict or preclude suicide. Even so, attempting to evaluate an individual’s risk by asking about suicidal thinking, reviewing risk factors, or using clinical rating scales helps you determine the next appropriate action (discharge, medication, psychiatric referral, consultation, or hospitalization).

While talking to patients and evaluating their risk for suicide, you may begin to understand their suffering—described as the most common denominator in suicide² and perhaps the most important clue to heightened suicide risk. Such an exploration allows you to identify potential:

• risk factors that can be modified
• preventative factors to promote.

Don’t be afraid to ask. Asking about suicidal thoughts is necessary—but not enough—to understand an individual’s potential for suicide. Never be afraid to ask patients about suicide, believing that doing so will “put ideas into their heads.” By the same token, a patient who denies thoughts or plans for suicide may still be at risk.

Identifying at-risk patients is much more difficult than just asking if they are considering suicide. Opening a concerned dialogue can provide a sense of relief to the patient while allowing you to explore:

• the extent and seriousness of the suicidal thoughts
• associated risk factors or conditions, such as depression.

Stepwise risk assessment

The first 3 steps of Jacobs’ B-SAFE model focus on identifying predisposing and protective factors for suicide.³ For an in-depth discussion, consult the American Psychiatric Association practice guideline for the assessment and treatment of patients with suicidal behaviors⁴ (available at http://www.psych.org/psych_pract/treatg/pg/suicidalbehavior_05-15-06.pdf).

STEP 1: Risk factors. Use the patient interview, medical records, and collateral information to uncover potential suicide risk factors (Table 1).²

Psychopathology. Focus on depression, bipolar disorder, schizophrenia, substance abuse, and personality disorders, which are strongly associated with suicide. These disorders are considered modifiable risk factors—diagnosis and appropriate treatment can diminish suicide risk.

Suicidality has been associated with early depression or bipolar disorder, often before patients receive a diagnosis or effective treatment. Recovery and immediate post-discharge periods also are thought to be times of heightened suicide risk.

Psychosocial variables. Demographic and psychosocial variables may influence suicide risk estimation. A retrospective study of 100 patients who attempted suicide suggests that the most predictive factors for suicide are:

• living alone
• being aged 17 to 35 (although in other studies, more advanced age also has been linked to increased suicide risk³)
• complaints of severe hopelessness, anhedonia, and insomnia.⁵

Physical illness may potentiate suicide risk. Medical illnesses that produce great pain, disfigurement, limited function, or fear of dependence may reduce a person’s will to live and increase suicide risk.⁶ Epilepsy has been associated with a 4- to 5-fold increase in suicide risk⁷ and is the only medical diagnosis to carry a documented increase in suicide among children and adolescents.⁸ Often these medical disorders coexist with psychiatric disorders, complicating the task of determining independent risk.

Severity of attempts or self-mutilation. When evaluating self-injurious or suicidal behavior in the emergency setting, consider the severity of the attempt as part of overall suicide assessment. Self-injurious behavior (cutting or burning) or impulsive suicide attempts (planned for <3 hours, committed in the presence others, or where discovery is very probable) appear to carry less severity or intent to die than do carefully planned and/or hidden suicide attempts.⁹ However, consider at high risk for suicide any patient with self-mutilating or suicidal behavior who expresses persistent intent to die; acute stabilization on an in-patient unit may be necessary.

STEP 2: ‘Protective’ factors. Discover and discuss internal and external factors that might help prevent the individual with suicidal thoughts from converting those thoughts into action (Table 2).² When discussing these potentially protective effects, emphasize the patient’s:

• resilience during past personal crises
• family responsibilities
• religious or spiritual beliefs.

‘No-harm contracts.’ Suicide (or “no-harm”) contracts with patients might help open communication about factors that promote or mitigate suicide risk. Such contacts do not prevent suicide or lessen medicolegal risk in the event of a patient suicide, however.¹⁰

STEP 3: Suicide plans. Ask about suicide thoughts, plans, and behaviors (Table 3).¹¹ Probe gently to allow the individual to discuss his or her feelings and to explore the next appropriate avenue of care.

In my experience, patients who reveal passive suicidal ideation (such as, “I sometimes wish I would just die in my sleep”) and strong deterrents to acting on thoughts of suicide (such as, “My children need me,” or “It’s against my religion”) should continue outpatient treatment. Those without deterrents or who discuss active and imminent thoughts and recent actions—writing suicide notes, buying a weapon, stockpiling pills—require emergent evaluation for psychiatric admission. Ask about thoughts of self-injury or mutilation (such as cutting or burning), as well as homicidal ideation.

Recognizing that patients with suicidal thoughts are almost always ambivalent about suicide to some extent—conflicted by simultaneous desires to live and to die—gives you the opportunity to intervene by allying with the part of the patient that wants to live. Creating a therapeutic connection also will help you determine the level of intervention required.

STEP 4: Intervention. Understanding why a patient feels suicidal—gathered in Steps 1 to 3—can help you choose the appropriate intervention. Among the 5 steps, Step 4 relies most heavily on clinical judgment:

• Is the suicidality acute or chronic?
• How great is the risk for suicide?
• To keep the patient safe, how urgent is the required intervention?

Acute risk. Suicidality related to Axis I psychiatric disorders tends to be acute, with prominent pain, anguish, and a desire to escape. Patients may describe a driven quality to the suicidality, which commands a treatment plan that maintains patient safety until suicidal feelings remit.

Hospitalization is often needed, plus focused treatments such as medication, psychotherapy, or electroconvulsive therapy. Intensive outpatient follow-up or partial hospitalization programs might be considered for patients:

• with whom you have a strong therapeutic alliance
• who have sturdy psychosocial support
• whose precipitating factors for suicidality have resolved.

Chronic risk. Suicide risk tends to be more chronic and has an impulsive quality for patients with suicidality related to personality disorders and environmental factors. Personality disordered patients may report feelings of anger, rage, or vengeance connected with their suicidal thoughts.

Hospitalization might become necessary, although multiple hospitalizations can be counter-therapeutic. Attempting in therapy to teach the patient to cope with suicidal thoughts and feelings might be a more effective intervention.

Malingering. Use your best judgment when patients make suicide threats that could represent malingering to achieve hospitalization.

Step 5: Documentation. Document your assessment of the suicidal patient and decision making to:

• clarify the treatment plan
• communicate to other caregivers
• manage medicolegal risk.

Include a brief summary (Box) that is timely, legible, and communicates the estimated degree of risk, known data, diagnosis, and planned interventions such as medications, tests, consultations, and follow-up reassessments.

Box

Table 1

Factors associated with potential for increased suicide risk

Table 2

Potentially protective factors against suicide

Table 3

Evaluating suicide risk: Questions to ask patients

Interventions for suicidal patients

Physical protection. Take decisive action when you determine that suicide risk is elevated and imminent. Pursue urgent psychiatric hospitalization, with or without patient consent, in accordance with local probate and involuntary commitment statutes.

The logistics of protective action can be challenging; transportation is often required, and the patient is not always cooperative with admission. Table 4 lists measures and precautions that can help keep the suicidal patient safe.

Disease-specific interventions. Because suicidal ideation is often symptomatic of a primary psychiatric disorder, rapidly identifying major depression, bipolar disorder, or a psychotic illness is crucial to reducing suicidal thoughts and behaviors. Prescribe appropriate antidepressants, mood stabilizers, and antipsychotics at adequate doses and for sufficient duration.

Be vigilant for distressing symptoms that may be elevating the patient’s suicide risk, such as anxiety, panic, agitation, insomnia, or pain. Pharmacotherapies—such as anxiolytics, sedative-hypnotics, antipsychotics, or analgesics—may rapidly reduce suffering.

Impulsivity associated with substance use disorders—particularly during intoxication and withdrawal syndromes—requires aggressive attempts by the treatment team to engage the patient in detoxification and rehabilitation.

Direct antisuicide therapy. Clozapine carries an FDA-approved indication for preventing suicide in patients with schizophrenia or schizoaffective disorder. The mechanism by which clozapine helps prevent suicide is not known, but its anti-suicidal effects appear to be independent of its antipsychotic effects.¹²

Lithium has been reported to reduce risk of suicide and suicide attempts in patients with bipolar disorder, perhaps by as much as 80%.¹³ Such benefit has not been observed with other mood stabilizers, suggesting that lithium confers protective effects against suicide beyond its mood-stabilizing effects. Suicide risk is known to increase after lithium is discontinued.¹⁴

Lithium’s antisuicidal effects may arise from its ability to enhance serotonin. This theory, although unproven, is consistent with observations associating central serotonergic deficiency with suicidal and aggressive behaviors.

Psychosocial measures. Address psychosocial variables that may increase suicide risk (Table 1). Recruit and involve the patient’s support system, augmented with a close follow-up plan. Case management to explore housing and job opportunities can help. Work with the patient’s family or others to remove guns from the patient’s access. Individual, marital, and family therapies can reduce conflicts and strengthen coping skills.

Table 4

Safety measures to protect the suicidal patient

Related resources

• National Suicide Prevention Lifeline, sponsored by the Substance Abuse & Mental Health Services Administration: 1-800-SUICIDE or 1-800-273-TALK (8255); www.suicidepreventionlifeline.org.
• American Foundation for Suicide Prevention (AFSP) 1-888-333-AFSP; www.afsp.org.
• Simon RI, Hales RE. Textbook of suicide assessment and management. Washington, DC: American Psychiatric Publishing; 2006.

Drug brand names

• Clozapine • Clozaril
• Lithium • Eskalith, Lithobid, others

Disclosure

Dr. Muzina has received grants from or served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Novartis Pharmaceuticals Corp., Pfizer, and Repligen.

More than 50% of psychiatrists have experienced the death of a patient by suicide.¹ For many of us, suicide represents the most feared outcome of a patient’s mental illness and makes managing suicide risk critical to everyday practice.

Unfortunately, we have little ability to predict suicide. Research into risk factors and the use of suicide rating scales have produced no consistently definitive methods to determine who will and who will not attempt or complete suicide.² The purpose of suicide assessment, then, is not to predict suicide but to help us understand the sources of a patient’s suicidality and develop an informed intervention.

This article describes a practical, commonly accepted approach to suicide risk assessment and intervention, based on the B-SAFE model (Basic Suicide Assessment Five-step Evaluation) proposed by Jacobs et al (Figure).³ Using this method to assess suicide risk can help you answer questions such as:

• Which factors are most important to consider when evaluating suicide risk in my patient?
• What questions should I ask my patient to find out if he or she is suicidal?
• How do I know if a patient is at risk for suicide?
• What emergent interventions are called for when managing the acutely suicidal patient?
• How should I document a suicide risk assessment?

Figure Basic Suicide Assessment Five-step Evaluation (B-SAFE)

Source: Created from information in references 2,11

Why ask about suicide?

No single risk factor or combination of risk factors can predict or preclude suicide. Even so, attempting to evaluate an individual’s risk by asking about suicidal thinking, reviewing risk factors, or using clinical rating scales helps you determine the next appropriate action (discharge, medication, psychiatric referral, consultation, or hospitalization).

While talking to patients and evaluating their risk for suicide, you may begin to understand their suffering—described as the most common denominator in suicide² and perhaps the most important clue to heightened suicide risk. Such an exploration allows you to identify potential:

• risk factors that can be modified
• preventative factors to promote.

Don’t be afraid to ask. Asking about suicidal thoughts is necessary—but not enough—to understand an individual’s potential for suicide. Never be afraid to ask patients about suicide, believing that doing so will “put ideas into their heads.” By the same token, a patient who denies thoughts or plans for suicide may still be at risk.

Identifying at-risk patients is much more difficult than just asking if they are considering suicide. Opening a concerned dialogue can provide a sense of relief to the patient while allowing you to explore:

• the extent and seriousness of the suicidal thoughts
• associated risk factors or conditions, such as depression.

Stepwise risk assessment

The first 3 steps of Jacobs’ B-SAFE model focus on identifying predisposing and protective factors for suicide.³ For an in-depth discussion, consult the American Psychiatric Association practice guideline for the assessment and treatment of patients with suicidal behaviors⁴ (available at http://www.psych.org/psych_pract/treatg/pg/suicidalbehavior_05-15-06.pdf).

STEP 1: Risk factors. Use the patient interview, medical records, and collateral information to uncover potential suicide risk factors (Table 1).²

Psychopathology. Focus on depression, bipolar disorder, schizophrenia, substance abuse, and personality disorders, which are strongly associated with suicide. These disorders are considered modifiable risk factors—diagnosis and appropriate treatment can diminish suicide risk.

Suicidality has been associated with early depression or bipolar disorder, often before patients receive a diagnosis or effective treatment. Recovery and immediate post-discharge periods also are thought to be times of heightened suicide risk.

Psychosocial variables. Demographic and psychosocial variables may influence suicide risk estimation. A retrospective study of 100 patients who attempted suicide suggests that the most predictive factors for suicide are:

• living alone
• being aged 17 to 35 (although in other studies, more advanced age also has been linked to increased suicide risk³)
• complaints of severe hopelessness, anhedonia, and insomnia.⁵

Physical illness may potentiate suicide risk. Medical illnesses that produce great pain, disfigurement, limited function, or fear of dependence may reduce a person’s will to live and increase suicide risk.⁶ Epilepsy has been associated with a 4- to 5-fold increase in suicide risk⁷ and is the only medical diagnosis to carry a documented increase in suicide among children and adolescents.⁸ Often these medical disorders coexist with psychiatric disorders, complicating the task of determining independent risk.

Severity of attempts or self-mutilation. When evaluating self-injurious or suicidal behavior in the emergency setting, consider the severity of the attempt as part of overall suicide assessment. Self-injurious behavior (cutting or burning) or impulsive suicide attempts (planned for <3 hours, committed in the presence others, or where discovery is very probable) appear to carry less severity or intent to die than do carefully planned and/or hidden suicide attempts.⁹ However, consider at high risk for suicide any patient with self-mutilating or suicidal behavior who expresses persistent intent to die; acute stabilization on an in-patient unit may be necessary.

STEP 2: ‘Protective’ factors. Discover and discuss internal and external factors that might help prevent the individual with suicidal thoughts from converting those thoughts into action (Table 2).² When discussing these potentially protective effects, emphasize the patient’s:

• resilience during past personal crises
• family responsibilities
• religious or spiritual beliefs.

‘No-harm contracts.’ Suicide (or “no-harm”) contracts with patients might help open communication about factors that promote or mitigate suicide risk. Such contacts do not prevent suicide or lessen medicolegal risk in the event of a patient suicide, however.¹⁰

STEP 3: Suicide plans. Ask about suicide thoughts, plans, and behaviors (Table 3).¹¹ Probe gently to allow the individual to discuss his or her feelings and to explore the next appropriate avenue of care.

In my experience, patients who reveal passive suicidal ideation (such as, “I sometimes wish I would just die in my sleep”) and strong deterrents to acting on thoughts of suicide (such as, “My children need me,” or “It’s against my religion”) should continue outpatient treatment. Those without deterrents or who discuss active and imminent thoughts and recent actions—writing suicide notes, buying a weapon, stockpiling pills—require emergent evaluation for psychiatric admission. Ask about thoughts of self-injury or mutilation (such as cutting or burning), as well as homicidal ideation.

Recognizing that patients with suicidal thoughts are almost always ambivalent about suicide to some extent—conflicted by simultaneous desires to live and to die—gives you the opportunity to intervene by allying with the part of the patient that wants to live. Creating a therapeutic connection also will help you determine the level of intervention required.

STEP 4: Intervention. Understanding why a patient feels suicidal—gathered in Steps 1 to 3—can help you choose the appropriate intervention. Among the 5 steps, Step 4 relies most heavily on clinical judgment:

• Is the suicidality acute or chronic?
• How great is the risk for suicide?
• To keep the patient safe, how urgent is the required intervention?

Acute risk. Suicidality related to Axis I psychiatric disorders tends to be acute, with prominent pain, anguish, and a desire to escape. Patients may describe a driven quality to the suicidality, which commands a treatment plan that maintains patient safety until suicidal feelings remit.

Hospitalization is often needed, plus focused treatments such as medication, psychotherapy, or electroconvulsive therapy. Intensive outpatient follow-up or partial hospitalization programs might be considered for patients:

• with whom you have a strong therapeutic alliance
• who have sturdy psychosocial support
• whose precipitating factors for suicidality have resolved.

Chronic risk. Suicide risk tends to be more chronic and has an impulsive quality for patients with suicidality related to personality disorders and environmental factors. Personality disordered patients may report feelings of anger, rage, or vengeance connected with their suicidal thoughts.

Hospitalization might become necessary, although multiple hospitalizations can be counter-therapeutic. Attempting in therapy to teach the patient to cope with suicidal thoughts and feelings might be a more effective intervention.

Malingering. Use your best judgment when patients make suicide threats that could represent malingering to achieve hospitalization.

Step 5: Documentation. Document your assessment of the suicidal patient and decision making to:

• clarify the treatment plan
• communicate to other caregivers
• manage medicolegal risk.

Include a brief summary (Box) that is timely, legible, and communicates the estimated degree of risk, known data, diagnosis, and planned interventions such as medications, tests, consultations, and follow-up reassessments.

Box

Table 1

Factors associated with potential for increased suicide risk

Table 2

Potentially protective factors against suicide

Table 3

Evaluating suicide risk: Questions to ask patients

Interventions for suicidal patients

Physical protection. Take decisive action when you determine that suicide risk is elevated and imminent. Pursue urgent psychiatric hospitalization, with or without patient consent, in accordance with local probate and involuntary commitment statutes.

The logistics of protective action can be challenging; transportation is often required, and the patient is not always cooperative with admission. Table 4 lists measures and precautions that can help keep the suicidal patient safe.

Disease-specific interventions. Because suicidal ideation is often symptomatic of a primary psychiatric disorder, rapidly identifying major depression, bipolar disorder, or a psychotic illness is crucial to reducing suicidal thoughts and behaviors. Prescribe appropriate antidepressants, mood stabilizers, and antipsychotics at adequate doses and for sufficient duration.

Be vigilant for distressing symptoms that may be elevating the patient’s suicide risk, such as anxiety, panic, agitation, insomnia, or pain. Pharmacotherapies—such as anxiolytics, sedative-hypnotics, antipsychotics, or analgesics—may rapidly reduce suffering.

Impulsivity associated with substance use disorders—particularly during intoxication and withdrawal syndromes—requires aggressive attempts by the treatment team to engage the patient in detoxification and rehabilitation.

Direct antisuicide therapy. Clozapine carries an FDA-approved indication for preventing suicide in patients with schizophrenia or schizoaffective disorder. The mechanism by which clozapine helps prevent suicide is not known, but its anti-suicidal effects appear to be independent of its antipsychotic effects.¹²

Lithium has been reported to reduce risk of suicide and suicide attempts in patients with bipolar disorder, perhaps by as much as 80%.¹³ Such benefit has not been observed with other mood stabilizers, suggesting that lithium confers protective effects against suicide beyond its mood-stabilizing effects. Suicide risk is known to increase after lithium is discontinued.¹⁴

Lithium’s antisuicidal effects may arise from its ability to enhance serotonin. This theory, although unproven, is consistent with observations associating central serotonergic deficiency with suicidal and aggressive behaviors.

Psychosocial measures. Address psychosocial variables that may increase suicide risk (Table 1). Recruit and involve the patient’s support system, augmented with a close follow-up plan. Case management to explore housing and job opportunities can help. Work with the patient’s family or others to remove guns from the patient’s access. Individual, marital, and family therapies can reduce conflicts and strengthen coping skills.

Table 4

Safety measures to protect the suicidal patient

Related resources

• National Suicide Prevention Lifeline, sponsored by the Substance Abuse & Mental Health Services Administration: 1-800-SUICIDE or 1-800-273-TALK (8255); www.suicidepreventionlifeline.org.
• American Foundation for Suicide Prevention (AFSP) 1-888-333-AFSP; www.afsp.org.
• Simon RI, Hales RE. Textbook of suicide assessment and management. Washington, DC: American Psychiatric Publishing; 2006.

Drug brand names

• Clozapine • Clozaril
• Lithium • Eskalith, Lithobid, others

Disclosure

Dr. Muzina has received grants from or served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Novartis Pharmaceuticals Corp., Pfizer, and Repligen.

Mr. W, age 51, received an implantable cardioverter defibrillator (ICD) after a diagnosis of ventricular tachycardia. He has lived more than 2 years without an ICD discharge and had been functioning well.

One evening, while watching his favorite football team lose a close, intense game on television, Mr. W receives his first ICD “shock.” He becomes extremely anxious and immediately associates the shock with the anger and frustration he was feeling while watching the game. He also suspects he might have caused the shock by using the remote control to change channels when he realized his team would lose.

Anxiety, depression, and feeling a “loss of control” are common among ICD patients. Although the devices provide cardiac patients with a better quality of life than the use of antiarrhythmia drugs,¹ ICD recipients may live in fear of receiving a powerful shock at any moment.

This article explains how to break the “fear of fear” cycle that causes ICD patients to avoid activities they associate with ICD activation. To help you preserve ICD patients’ functioning, we describe:

• common psychiatric symptoms in ICD recipients
• when and how to assess for ICD-related anxiety
• cognitive-behavioral and pharmacotherapeutic options.

A psychological jolt

An ICD acts to prevent sudden cardiac death (Box 1)^2-7 when a patient develops a sustained, potentially life-threatening arrhythmia. The device restores normal cardiac rhythm by delivering high-energy electrical pulses (shocks) to the appropriate chamber in the patient’s heart (Box 2).

Patients usually perceive ICD shocks as painful and unpleasant, which can cause fear, anger, anxiety, helplessness, and depression.^8-11 The ICD recipient’s cardiac status, history of psychiatric illness, and other factors increase the risk of experiencing these symptoms (Table 1).^8,9

Undergoing the implantation of an ICD may cause patients to feel a loss of personal, social, and material resources. The higher the ICD recipient’s sense of loss of financial or physical well-being, the higher the risk of depression and anxiety.⁹

Inadequate social support, poor physical functioning, a
history of depression, and greater length of time
since ICD implantation also may contribute
to emotional distress.⁹

Besides having undergone cardiac surgery, patients with newly implanted ICDs face other stressors, including:

• expensive medical bills
• possible disability
• driving restrictions.

Patients’ personal relationships may become strained because of changes in their ability to maintain previous physical, social, and sexual activity. Depression or anxiety can cause patients to be withdrawn or irritable.

Some ICD recipients become concerned with body image because the silhouette of the device may be visible under the skin. After ICD implantation, patients may become more aware that they may experience life-threatening arrhythmias.

Finally—and perhaps most important to the patient and psychiatrist—a recipient might be constantly afraid that the device is about to deliver a shock.⁸

Box 1

Table 1

5 risk factors for ICD-related psychiatric symptoms

Fear impairs functioning

Experiencing an ICD discharge can affect patients’ appraisal of their situation and impair functioning.

CASE CONTINUED: Anxiety leads to avoidance

After receiving the ICD shock, Mr. W stops watching his favorite teams on television. He later ceases viewing sporting events, and over the next several months stops watching television altogether.

Mr. W continues to experience severe anxiety and ruminates about potential shocks. He believes that as long as he avoids becoming “excited” he can reduce his risk of shock. He comes to believe that his avoidance accounts for the absence of subsequent shocks and therefore continues to alter his lifestyle. Mr. W begins to eliminate other behaviors, including sex and exercise, that he fears might induce an ICD shock.

Avoiding activities. After receiving a shock, patients often develop fear that causes them to avoid the activity they were doing when the discharge occurred. This classical conditioning process often leads patients to continually avoid the activity, which may reduce anxiety but is negatively reinforcing (operant conditioning).

These fears and subsequent avoidance behaviors may increase with the number of shocks.⁸ Over time, fear and avoidance may adversely alter lifestyle and diminish quality of life.

Hypervigilance to physical sensations. Patients typically are troubled by ICDs’ uncontrollable, unpredictable nature and feel compelled to try to predict when the device will fire. Often patients become attuned to minor physical sensations and incorrectly interpret normal sympathetic sensations as precursors of an ICD discharge. Fearful assessment of these symptoms can activate anxiety-related sympathetic arousal, creating a “fear of fear” cycle that mimics the catastrophic interpretation of panic disorder patients.¹⁰

Cognitive distortions. After receiving an ICD discharge, patients commonly “catastrophize” about future events. They might overestimate the negative consequences of a discharge by, for example, thinking that if they are shocked during an important event, it will ruin the event for everyone.

“Overgeneralizing” occurs when patients believe a rare occurrence (an ICD discharge) will happen frequently, which may contribute to avoidance. For example, patients might think they should avoid the grocery store if they previously received a shock while shopping.

Phantom shocks. A patient with an ICD may insist he has experienced a shock even though the device provides no evidence of delivering one. Patients may report feeling kicked, shaken, or jolted out of sleep.

Because re-experiencing an event (in this case, through phantom shocks), avoidance, and hyperarousal are part of DSM-IV-TR criteria for posttraumatic stress disorder (PTSD), some clinicians equate patients’ post-shock experience to PTSD.¹¹ The more often patients are shocked, the more likely they will experience these outcomes.

CASE CONTINUED: Delayed diagnosis

As a result of his drastic lifestyle changes, Mr. W experiences considerable relationship, vocational, and financial problems. Unfortunately, Mr. W’s primary care physician doesn’t recognize the impact of these symptoms until Mr. W becomes severely depressed. Then Mr. W is referred for psychiatric treatment.

Box 2

Placement of an implantable cardioverter defibrillator

During implantation, the surgeon places the ICD under the skin in the upper chest beneath the patient’s collarbone or abdominal muscles. Each lead is threaded through the subclavian or cephalic vein, passed into the appropriate cardiac chamber, and anchored with a soft prong or screw.

Table 2

Self-rated Florida Shock Anxiety Scale for ICD patients*

Frequent assessment is key

ICD patients should be assessed for psychiatric symptoms soon after the device is implanted and consistently as a part of routine medical care. At all follow-up visits, primary care clinicians should screen patients for anxiety, depression, and difficulty adjusting to receiving an ICD, and refer those who exhibit signs and symptoms of emotional distress to a mental health professional for evaluation and treatment.

ICD patients might not readily report psychiatric symptoms because of embarrassment, lack of insight, or the circumscribed nature of their symptoms. Because patients may have symptoms that do not meet diagnostic criteria for a specific DSM-IV-TR disorder but impair quality of life and functioning, assess for subclinical distress. Assess patients regularly even if they have not experienced a shock because device-related distress can occur in the absence of shock.

Frequently used screening instruments for anxiety and depression—such as the Beck Depression Inventory, Beck Anxiety Inventory, Brief Symptom Inventory-18 Item, and the Patient Health Questionnaire—can be helpful. Some patients’ distress is limited to their ICDs, however, and cannot be identified by more general measures.

As with Mr. W, traditional inventories might not detect the severity of ICD patients’ psychiatric symptoms until symptoms are severe. Moreover, initial symptoms can be very specific to the ICD and, to some clinicians, may seem relatively benign. Using an instrument designed specifically for assessing ICD patients can lead to earlier diagnosis and treatment.

ICD-specific tools. The Florida Shock Anxiety Scale (FSAS) is a 10-item questionnaire measuring ICD-specific fears about shock (Table 2).¹² The FSAS contains statements, such as “I have unwanted thoughts of my ICD firing” and “When I note my heart beating rapidly, I worry that the ICD will fire,” that patients rate on a scale of 1 (Not at all) to 5 (All of the time). A patient who scores 3 or higher on any item should receive counseling related to his specific concerns.

Another useful instrument is the ICD Patient Concerns Questionnaire,¹³ a 20-item questionnaire to assess the number and severity of ICD recipients’ concerns. Both instruments can help identify targets for intervention.

Targeting underlying beliefs

The initial treatment goal is to relieve anxiety and depressive symptoms. These are likely to persist, however, if the patient’s irrational beliefs, avoidance, and conditioning are not addressed.

Treatment often involves a combination of medication, psychotherapy, and support. Anxiolytics and antidepressants may prove helpful. Choose medications—in collaboration with the patient’s electrophysiologist— based on the patient’s medical history, psychiatric history, and other factors.

Cognitive-behavioral therapy (CBT) often is used to identify and correct maladaptive or irrational beliefs about ICDs and shocks and to eliminate avoidance behaviors that serve as negative reinforcement. CBT typically begins with psychoeducation about the ICD to help patients realize their thoughts about the device might be irrational. Strategies include keeping a daily log of ICD-related thoughts and cognitive re-structuring. Exposure therapy can help patients re-engage in activities they have been avoiding because of irrational fears.

One study found that ICD patients who received CBT that included psychoeducation, stress management, addressing distorted cognitions and avoidance behavior, and resuming work and social activities had less depression and anxiety and better overall adjustment than those who did not get CBT, whether or not their ICD had ever delivered a shock.¹⁴

Smith et al¹⁵ demonstrated the effectiveness of CBT in patients with ICDs who suffer from panic disorder with agoraphobia and depression. This treatment included:

• interoceptive exposure to target somatic hypervigilance
• relaxation techniques
• cognitive restructuring.

Other therapeutic interventions that can help patients cope and improve their quality of life include support groups, relaxation training, biofeedback, and couples’ counseling.^16-19

CASE CONTINUED: CBT helps patient resume activities CBT helps patient resume activities

During 8 CBT sessions, Mr. W learns to identify and challenge the irrational and maladaptive beliefs that were leading him to avoid numerous activities. He eventually accepts that watching television is not likely by itself to trigger an ICD discharge. Through a combination of exposure therapy and relaxation training, Mr. W can resume most activities, which improves his personal relationships and quality of life.

Related resources

• Frizelle D, Lewin B, Kaye G, Moniz-Cook E. Development of a measure of the concerns held by people with implanted cardioverter defibrillators: the ICDC. Br J Health Psychol 2006;11:293-301.
• Hecksel KA, Bostwick JM. Getting to the heart of his 'shocking' trauma. Current Psychiatry 2007;6(6):84-95.
• Kuhl E, Dixit N, Walker R, et al. Measurement of patient fears about implantable cardioverter defibrillator shock: an initial evaluation of the Florida Shock Anxiety Scale. Pacing Clin Electrophysiol 2006;29:614-8.
• Thomas S, Friedmann E, Kao C, et al. Quality of life and psychological status of patients with implantable cardioverter defibrillators. Am J Crit Care 2006;15(4):389-98.

Disclosure

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

Mr. W, age 51, received an implantable cardioverter defibrillator (ICD) after a diagnosis of ventricular tachycardia. He has lived more than 2 years without an ICD discharge and had been functioning well.

One evening, while watching his favorite football team lose a close, intense game on television, Mr. W receives his first ICD “shock.” He becomes extremely anxious and immediately associates the shock with the anger and frustration he was feeling while watching the game. He also suspects he might have caused the shock by using the remote control to change channels when he realized his team would lose.

Anxiety, depression, and feeling a “loss of control” are common among ICD patients. Although the devices provide cardiac patients with a better quality of life than the use of antiarrhythmia drugs,¹ ICD recipients may live in fear of receiving a powerful shock at any moment.

This article explains how to break the “fear of fear” cycle that causes ICD patients to avoid activities they associate with ICD activation. To help you preserve ICD patients’ functioning, we describe:

• common psychiatric symptoms in ICD recipients
• when and how to assess for ICD-related anxiety
• cognitive-behavioral and pharmacotherapeutic options.

A psychological jolt

An ICD acts to prevent sudden cardiac death (Box 1)^2-7 when a patient develops a sustained, potentially life-threatening arrhythmia. The device restores normal cardiac rhythm by delivering high-energy electrical pulses (shocks) to the appropriate chamber in the patient’s heart (Box 2).

Patients usually perceive ICD shocks as painful and unpleasant, which can cause fear, anger, anxiety, helplessness, and depression.^8-11 The ICD recipient’s cardiac status, history of psychiatric illness, and other factors increase the risk of experiencing these symptoms (Table 1).^8,9

Undergoing the implantation of an ICD may cause patients to feel a loss of personal, social, and material resources. The higher the ICD recipient’s sense of loss of financial or physical well-being, the higher the risk of depression and anxiety.⁹

Inadequate social support, poor physical functioning, a
history of depression, and greater length of time
since ICD implantation also may contribute
to emotional distress.⁹

Besides having undergone cardiac surgery, patients with newly implanted ICDs face other stressors, including:

• expensive medical bills
• possible disability
• driving restrictions.

Patients’ personal relationships may become strained because of changes in their ability to maintain previous physical, social, and sexual activity. Depression or anxiety can cause patients to be withdrawn or irritable.

Some ICD recipients become concerned with body image because the silhouette of the device may be visible under the skin. After ICD implantation, patients may become more aware that they may experience life-threatening arrhythmias.

Finally—and perhaps most important to the patient and psychiatrist—a recipient might be constantly afraid that the device is about to deliver a shock.⁸

Box 1

Table 1

5 risk factors for ICD-related psychiatric symptoms

Fear impairs functioning

Experiencing an ICD discharge can affect patients’ appraisal of their situation and impair functioning.

CASE CONTINUED: Anxiety leads to avoidance

After receiving the ICD shock, Mr. W stops watching his favorite teams on television. He later ceases viewing sporting events, and over the next several months stops watching television altogether.

Mr. W continues to experience severe anxiety and ruminates about potential shocks. He believes that as long as he avoids becoming “excited” he can reduce his risk of shock. He comes to believe that his avoidance accounts for the absence of subsequent shocks and therefore continues to alter his lifestyle. Mr. W begins to eliminate other behaviors, including sex and exercise, that he fears might induce an ICD shock.

Avoiding activities. After receiving a shock, patients often develop fear that causes them to avoid the activity they were doing when the discharge occurred. This classical conditioning process often leads patients to continually avoid the activity, which may reduce anxiety but is negatively reinforcing (operant conditioning).

These fears and subsequent avoidance behaviors may increase with the number of shocks.⁸ Over time, fear and avoidance may adversely alter lifestyle and diminish quality of life.

Hypervigilance to physical sensations. Patients typically are troubled by ICDs’ uncontrollable, unpredictable nature and feel compelled to try to predict when the device will fire. Often patients become attuned to minor physical sensations and incorrectly interpret normal sympathetic sensations as precursors of an ICD discharge. Fearful assessment of these symptoms can activate anxiety-related sympathetic arousal, creating a “fear of fear” cycle that mimics the catastrophic interpretation of panic disorder patients.¹⁰

Cognitive distortions. After receiving an ICD discharge, patients commonly “catastrophize” about future events. They might overestimate the negative consequences of a discharge by, for example, thinking that if they are shocked during an important event, it will ruin the event for everyone.

“Overgeneralizing” occurs when patients believe a rare occurrence (an ICD discharge) will happen frequently, which may contribute to avoidance. For example, patients might think they should avoid the grocery store if they previously received a shock while shopping.

Phantom shocks. A patient with an ICD may insist he has experienced a shock even though the device provides no evidence of delivering one. Patients may report feeling kicked, shaken, or jolted out of sleep.

Because re-experiencing an event (in this case, through phantom shocks), avoidance, and hyperarousal are part of DSM-IV-TR criteria for posttraumatic stress disorder (PTSD), some clinicians equate patients’ post-shock experience to PTSD.¹¹ The more often patients are shocked, the more likely they will experience these outcomes.

CASE CONTINUED: Delayed diagnosis

As a result of his drastic lifestyle changes, Mr. W experiences considerable relationship, vocational, and financial problems. Unfortunately, Mr. W’s primary care physician doesn’t recognize the impact of these symptoms until Mr. W becomes severely depressed. Then Mr. W is referred for psychiatric treatment.

Box 2

Placement of an implantable cardioverter defibrillator

During implantation, the surgeon places the ICD under the skin in the upper chest beneath the patient’s collarbone or abdominal muscles. Each lead is threaded through the subclavian or cephalic vein, passed into the appropriate cardiac chamber, and anchored with a soft prong or screw.

Table 2

Self-rated Florida Shock Anxiety Scale for ICD patients*

Frequent assessment is key

ICD patients should be assessed for psychiatric symptoms soon after the device is implanted and consistently as a part of routine medical care. At all follow-up visits, primary care clinicians should screen patients for anxiety, depression, and difficulty adjusting to receiving an ICD, and refer those who exhibit signs and symptoms of emotional distress to a mental health professional for evaluation and treatment.

ICD patients might not readily report psychiatric symptoms because of embarrassment, lack of insight, or the circumscribed nature of their symptoms. Because patients may have symptoms that do not meet diagnostic criteria for a specific DSM-IV-TR disorder but impair quality of life and functioning, assess for subclinical distress. Assess patients regularly even if they have not experienced a shock because device-related distress can occur in the absence of shock.

Frequently used screening instruments for anxiety and depression—such as the Beck Depression Inventory, Beck Anxiety Inventory, Brief Symptom Inventory-18 Item, and the Patient Health Questionnaire—can be helpful. Some patients’ distress is limited to their ICDs, however, and cannot be identified by more general measures.

As with Mr. W, traditional inventories might not detect the severity of ICD patients’ psychiatric symptoms until symptoms are severe. Moreover, initial symptoms can be very specific to the ICD and, to some clinicians, may seem relatively benign. Using an instrument designed specifically for assessing ICD patients can lead to earlier diagnosis and treatment.

ICD-specific tools. The Florida Shock Anxiety Scale (FSAS) is a 10-item questionnaire measuring ICD-specific fears about shock (Table 2).¹² The FSAS contains statements, such as “I have unwanted thoughts of my ICD firing” and “When I note my heart beating rapidly, I worry that the ICD will fire,” that patients rate on a scale of 1 (Not at all) to 5 (All of the time). A patient who scores 3 or higher on any item should receive counseling related to his specific concerns.

Another useful instrument is the ICD Patient Concerns Questionnaire,¹³ a 20-item questionnaire to assess the number and severity of ICD recipients’ concerns. Both instruments can help identify targets for intervention.

Targeting underlying beliefs

The initial treatment goal is to relieve anxiety and depressive symptoms. These are likely to persist, however, if the patient’s irrational beliefs, avoidance, and conditioning are not addressed.

Treatment often involves a combination of medication, psychotherapy, and support. Anxiolytics and antidepressants may prove helpful. Choose medications—in collaboration with the patient’s electrophysiologist— based on the patient’s medical history, psychiatric history, and other factors.

Cognitive-behavioral therapy (CBT) often is used to identify and correct maladaptive or irrational beliefs about ICDs and shocks and to eliminate avoidance behaviors that serve as negative reinforcement. CBT typically begins with psychoeducation about the ICD to help patients realize their thoughts about the device might be irrational. Strategies include keeping a daily log of ICD-related thoughts and cognitive re-structuring. Exposure therapy can help patients re-engage in activities they have been avoiding because of irrational fears.

One study found that ICD patients who received CBT that included psychoeducation, stress management, addressing distorted cognitions and avoidance behavior, and resuming work and social activities had less depression and anxiety and better overall adjustment than those who did not get CBT, whether or not their ICD had ever delivered a shock.¹⁴

Smith et al¹⁵ demonstrated the effectiveness of CBT in patients with ICDs who suffer from panic disorder with agoraphobia and depression. This treatment included:

• interoceptive exposure to target somatic hypervigilance
• relaxation techniques
• cognitive restructuring.

Other therapeutic interventions that can help patients cope and improve their quality of life include support groups, relaxation training, biofeedback, and couples’ counseling.^16-19

CASE CONTINUED: CBT helps patient resume activities CBT helps patient resume activities

During 8 CBT sessions, Mr. W learns to identify and challenge the irrational and maladaptive beliefs that were leading him to avoid numerous activities. He eventually accepts that watching television is not likely by itself to trigger an ICD discharge. Through a combination of exposure therapy and relaxation training, Mr. W can resume most activities, which improves his personal relationships and quality of life.

Related resources

• Frizelle D, Lewin B, Kaye G, Moniz-Cook E. Development of a measure of the concerns held by people with implanted cardioverter defibrillators: the ICDC. Br J Health Psychol 2006;11:293-301.
• Hecksel KA, Bostwick JM. Getting to the heart of his 'shocking' trauma. Current Psychiatry 2007;6(6):84-95.
• Kuhl E, Dixit N, Walker R, et al. Measurement of patient fears about implantable cardioverter defibrillator shock: an initial evaluation of the Florida Shock Anxiety Scale. Pacing Clin Electrophysiol 2006;29:614-8.
• Thomas S, Friedmann E, Kao C, et al. Quality of life and psychological status of patients with implantable cardioverter defibrillators. Am J Crit Care 2006;15(4):389-98.

Disclosure

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

Mr. W, age 51, received an implantable cardioverter defibrillator (ICD) after a diagnosis of ventricular tachycardia. He has lived more than 2 years without an ICD discharge and had been functioning well.

One evening, while watching his favorite football team lose a close, intense game on television, Mr. W receives his first ICD “shock.” He becomes extremely anxious and immediately associates the shock with the anger and frustration he was feeling while watching the game. He also suspects he might have caused the shock by using the remote control to change channels when he realized his team would lose.

Anxiety, depression, and feeling a “loss of control” are common among ICD patients. Although the devices provide cardiac patients with a better quality of life than the use of antiarrhythmia drugs,¹ ICD recipients may live in fear of receiving a powerful shock at any moment.

This article explains how to break the “fear of fear” cycle that causes ICD patients to avoid activities they associate with ICD activation. To help you preserve ICD patients’ functioning, we describe:

• common psychiatric symptoms in ICD recipients
• when and how to assess for ICD-related anxiety
• cognitive-behavioral and pharmacotherapeutic options.

A psychological jolt

An ICD acts to prevent sudden cardiac death (Box 1)^2-7 when a patient develops a sustained, potentially life-threatening arrhythmia. The device restores normal cardiac rhythm by delivering high-energy electrical pulses (shocks) to the appropriate chamber in the patient’s heart (Box 2).

Patients usually perceive ICD shocks as painful and unpleasant, which can cause fear, anger, anxiety, helplessness, and depression.^8-11 The ICD recipient’s cardiac status, history of psychiatric illness, and other factors increase the risk of experiencing these symptoms (Table 1).^8,9

Undergoing the implantation of an ICD may cause patients to feel a loss of personal, social, and material resources. The higher the ICD recipient’s sense of loss of financial or physical well-being, the higher the risk of depression and anxiety.⁹

Inadequate social support, poor physical functioning, a
history of depression, and greater length of time
since ICD implantation also may contribute
to emotional distress.⁹

Besides having undergone cardiac surgery, patients with newly implanted ICDs face other stressors, including:

• expensive medical bills
• possible disability
• driving restrictions.

Patients’ personal relationships may become strained because of changes in their ability to maintain previous physical, social, and sexual activity. Depression or anxiety can cause patients to be withdrawn or irritable.

Some ICD recipients become concerned with body image because the silhouette of the device may be visible under the skin. After ICD implantation, patients may become more aware that they may experience life-threatening arrhythmias.

Finally—and perhaps most important to the patient and psychiatrist—a recipient might be constantly afraid that the device is about to deliver a shock.⁸

Box 1

Table 1

5 risk factors for ICD-related psychiatric symptoms

Fear impairs functioning

Experiencing an ICD discharge can affect patients’ appraisal of their situation and impair functioning.

CASE CONTINUED: Anxiety leads to avoidance

After receiving the ICD shock, Mr. W stops watching his favorite teams on television. He later ceases viewing sporting events, and over the next several months stops watching television altogether.

Mr. W continues to experience severe anxiety and ruminates about potential shocks. He believes that as long as he avoids becoming “excited” he can reduce his risk of shock. He comes to believe that his avoidance accounts for the absence of subsequent shocks and therefore continues to alter his lifestyle. Mr. W begins to eliminate other behaviors, including sex and exercise, that he fears might induce an ICD shock.

Avoiding activities. After receiving a shock, patients often develop fear that causes them to avoid the activity they were doing when the discharge occurred. This classical conditioning process often leads patients to continually avoid the activity, which may reduce anxiety but is negatively reinforcing (operant conditioning).

These fears and subsequent avoidance behaviors may increase with the number of shocks.⁸ Over time, fear and avoidance may adversely alter lifestyle and diminish quality of life.

Hypervigilance to physical sensations. Patients typically are troubled by ICDs’ uncontrollable, unpredictable nature and feel compelled to try to predict when the device will fire. Often patients become attuned to minor physical sensations and incorrectly interpret normal sympathetic sensations as precursors of an ICD discharge. Fearful assessment of these symptoms can activate anxiety-related sympathetic arousal, creating a “fear of fear” cycle that mimics the catastrophic interpretation of panic disorder patients.¹⁰

Cognitive distortions. After receiving an ICD discharge, patients commonly “catastrophize” about future events. They might overestimate the negative consequences of a discharge by, for example, thinking that if they are shocked during an important event, it will ruin the event for everyone.

“Overgeneralizing” occurs when patients believe a rare occurrence (an ICD discharge) will happen frequently, which may contribute to avoidance. For example, patients might think they should avoid the grocery store if they previously received a shock while shopping.

Phantom shocks. A patient with an ICD may insist he has experienced a shock even though the device provides no evidence of delivering one. Patients may report feeling kicked, shaken, or jolted out of sleep.

Because re-experiencing an event (in this case, through phantom shocks), avoidance, and hyperarousal are part of DSM-IV-TR criteria for posttraumatic stress disorder (PTSD), some clinicians equate patients’ post-shock experience to PTSD.¹¹ The more often patients are shocked, the more likely they will experience these outcomes.

CASE CONTINUED: Delayed diagnosis

As a result of his drastic lifestyle changes, Mr. W experiences considerable relationship, vocational, and financial problems. Unfortunately, Mr. W’s primary care physician doesn’t recognize the impact of these symptoms until Mr. W becomes severely depressed. Then Mr. W is referred for psychiatric treatment.

Box 2

Placement of an implantable cardioverter defibrillator

During implantation, the surgeon places the ICD under the skin in the upper chest beneath the patient’s collarbone or abdominal muscles. Each lead is threaded through the subclavian or cephalic vein, passed into the appropriate cardiac chamber, and anchored with a soft prong or screw.

Table 2

Self-rated Florida Shock Anxiety Scale for ICD patients*

Frequent assessment is key

ICD patients should be assessed for psychiatric symptoms soon after the device is implanted and consistently as a part of routine medical care. At all follow-up visits, primary care clinicians should screen patients for anxiety, depression, and difficulty adjusting to receiving an ICD, and refer those who exhibit signs and symptoms of emotional distress to a mental health professional for evaluation and treatment.

ICD patients might not readily report psychiatric symptoms because of embarrassment, lack of insight, or the circumscribed nature of their symptoms. Because patients may have symptoms that do not meet diagnostic criteria for a specific DSM-IV-TR disorder but impair quality of life and functioning, assess for subclinical distress. Assess patients regularly even if they have not experienced a shock because device-related distress can occur in the absence of shock.

Frequently used screening instruments for anxiety and depression—such as the Beck Depression Inventory, Beck Anxiety Inventory, Brief Symptom Inventory-18 Item, and the Patient Health Questionnaire—can be helpful. Some patients’ distress is limited to their ICDs, however, and cannot be identified by more general measures.

As with Mr. W, traditional inventories might not detect the severity of ICD patients’ psychiatric symptoms until symptoms are severe. Moreover, initial symptoms can be very specific to the ICD and, to some clinicians, may seem relatively benign. Using an instrument designed specifically for assessing ICD patients can lead to earlier diagnosis and treatment.

ICD-specific tools. The Florida Shock Anxiety Scale (FSAS) is a 10-item questionnaire measuring ICD-specific fears about shock (Table 2).¹² The FSAS contains statements, such as “I have unwanted thoughts of my ICD firing” and “When I note my heart beating rapidly, I worry that the ICD will fire,” that patients rate on a scale of 1 (Not at all) to 5 (All of the time). A patient who scores 3 or higher on any item should receive counseling related to his specific concerns.

Another useful instrument is the ICD Patient Concerns Questionnaire,¹³ a 20-item questionnaire to assess the number and severity of ICD recipients’ concerns. Both instruments can help identify targets for intervention.

Targeting underlying beliefs

The initial treatment goal is to relieve anxiety and depressive symptoms. These are likely to persist, however, if the patient’s irrational beliefs, avoidance, and conditioning are not addressed.

Treatment often involves a combination of medication, psychotherapy, and support. Anxiolytics and antidepressants may prove helpful. Choose medications—in collaboration with the patient’s electrophysiologist— based on the patient’s medical history, psychiatric history, and other factors.

Cognitive-behavioral therapy (CBT) often is used to identify and correct maladaptive or irrational beliefs about ICDs and shocks and to eliminate avoidance behaviors that serve as negative reinforcement. CBT typically begins with psychoeducation about the ICD to help patients realize their thoughts about the device might be irrational. Strategies include keeping a daily log of ICD-related thoughts and cognitive re-structuring. Exposure therapy can help patients re-engage in activities they have been avoiding because of irrational fears.

One study found that ICD patients who received CBT that included psychoeducation, stress management, addressing distorted cognitions and avoidance behavior, and resuming work and social activities had less depression and anxiety and better overall adjustment than those who did not get CBT, whether or not their ICD had ever delivered a shock.¹⁴

Smith et al¹⁵ demonstrated the effectiveness of CBT in patients with ICDs who suffer from panic disorder with agoraphobia and depression. This treatment included:

• interoceptive exposure to target somatic hypervigilance
• relaxation techniques
• cognitive restructuring.

Other therapeutic interventions that can help patients cope and improve their quality of life include support groups, relaxation training, biofeedback, and couples’ counseling.^16-19

CASE CONTINUED: CBT helps patient resume activities CBT helps patient resume activities

During 8 CBT sessions, Mr. W learns to identify and challenge the irrational and maladaptive beliefs that were leading him to avoid numerous activities. He eventually accepts that watching television is not likely by itself to trigger an ICD discharge. Through a combination of exposure therapy and relaxation training, Mr. W can resume most activities, which improves his personal relationships and quality of life.

Related resources

• Frizelle D, Lewin B, Kaye G, Moniz-Cook E. Development of a measure of the concerns held by people with implanted cardioverter defibrillators: the ICDC. Br J Health Psychol 2006;11:293-301.
• Hecksel KA, Bostwick JM. Getting to the heart of his 'shocking' trauma. Current Psychiatry 2007;6(6):84-95.
• Kuhl E, Dixit N, Walker R, et al. Measurement of patient fears about implantable cardioverter defibrillator shock: an initial evaluation of the Florida Shock Anxiety Scale. Pacing Clin Electrophysiol 2006;29:614-8.
• Thomas S, Friedmann E, Kao C, et al. Quality of life and psychological status of patients with implantable cardioverter defibrillators. Am J Crit Care 2006;15(4):389-98.

Disclosure

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

When second-generation antipsychotics (SGAs) were introduced, clinicians hoped the drugs would not have the potential to cause neuroleptic malignant syndrome (NMS).¹ Since then, however, case reports have made it clear that SGAs—like first-generation antipsychotics (FGAs)—can precipitate this life-threatening neurologic emergency.

To help you protect your patients receiving SGAs, this article explains how to:

• identify those at risk
• recognize the different NMS presentations associated with each SGA
• continue antipsychotic treatment for a patient with a history of NMS.

CASE STUDY: A drug-induced disorder

Mrs. Z, age 39, has a history of multiple hospitalizations for schizoaffective disorder complicated by poor compliance and a history of benzodiazepine abuse. This time she was admitted with increased auditory hallucinations and paranoid delusions of her family trying to poison her. Despite multiple haloperidol injections (5 mg IM q4h prn), Mrs. Z continued to have hallucinations and remained agitated.

Haloperidol was discontinued and ziprasidone (20 mg IM q4h prn) was started. After 3 days, Mrs. Z became less agitated and had fewer hallucinations. The IM route was discontinued and oral ziprasidone was started at 40 mg bid, then titrated to 80 mg bid after 2 days. On the third day after titration, Mrs. Z fell twice. She hit her head in one fall, but a brain CT to rule out bleeding was normal.

The next day, Mrs. Z became more confused and developed fever, tremor, urinary incontinence, and a severe headache. She became obtunded, was intubated, and was transferred to the intensive care unit of a tertiary care center.

On admission, her temperature was 103° F (39.4° C); she had severe muscle rigidity and blood pressure of 85/60 mm Hg. Creatine phosphokinase (CPK) was 2,559 U/L (normal 24 to 170 U/L). Liver enzymes were elevated: alanine transaminase was 202 U/L (normal 13 to 50 U/L), and aspartate transaminase (AST) was 190 U/L (normal 15 to 46 U/L). At 140 μg/dL, Mrs. Z’s serum iron was within normal limits (40 to 150 μg/dL).

Neuroleptic malignant syndrome

Clinical manifestations of NMS range from typical—as defined by the DSM-IV-TR (Table 1)^2,3—to atypical, without:

• fever⁴
• rigidity⁵
• CPK elevation.

Table 1

DSM-IV-TR definition of NMS*

Many conditions resemble NMS (Table 2). Because NMS can be fatal without emergent diagnosis and treatment, maintain a high index of suspicion for this condition whenever you prescribe antipsychotics.

Table 2

NMS differential diagnosis

NMS is believed to be caused by reduced dopamine activity in the brain associated with dopamine antagonists, interruptions in nigrostriatal dopamine pathways, or withdrawal of dopaminergic medications.³ However, dopamine D₂ receptor blocking potential is not directly linked to the occurrence of NMS.⁶ Other mechanisms include genetic susceptibility and different CNS neurotransmitter disturbances.⁷

NMS develops in an estimated 0.02% to 2.5% of patients treated with antipsychotics.^8-10 The syndrome appears to occur slightly less frequently with SGAs than with FGAs.^6,10

Risk factors. NMS can develop at any age, in men and women, and in patients with psychiatric or medical illness.^11,12 In addition to antipsychotics, other medications—including antiemetics and sedatives—can cause NMS. The syndrome has been triggered when Parkinson’s disease patients stop taking or reduce the dose of a dopamine agonist or switch from 1 dopamine agonist to another.^13,14

Symptoms usually develop during the first 2 weeks of pharmacotherapy but may start after the initial dose or during long-term stable therapy.¹⁵ Although some studies found NMS development to be dose-independent, multiple cases have demonstrated an association with dose changes. Death occurs from dysautonomic manifestations and systemic complications.

An elevated risk for NMS may exist in patients with:

• mood disorders
• preexisting catatonia¹⁶
• complicated medical and neurologic disorders, such as encephalitis or mental retardation¹⁷
• poor functional and physiologic status³
• concurrent lithium treatment
• IM injection of an antipsychotic
• use of a high-potency antipsychotic, such as haloperidol
• psychomotor agitation.

Other potential risk factors include dehydration, adolescent age, male gender, low serum iron concentrations, relatively high antipsychotic dosages, and mental retardation or prior structural brain injury.^18-20

NMS and SGAs

We reviewed 88 reports of NMS cases associated with 6 SGAs: olanzapine, clozapine, risperidone, ziprasidone, quetiapine, and aripiprazole. In this article, we cite representative cases only; readers interested in the full literature search can find this evidence and its references in the Case Reports Table.

NMS cases were fairly evenly distributed across all age groups (Figure 1). SGAs were implicated in NMS when used as monotherapy in 9 cases (10%) and in combination with other psychotropics in 41 cases (47%). We could not find medication regimen data for 38 cases (43%).

Figure 1
NMS incidence across age groups

Incidence is dispersed fairly evenly; elderly patients may be less likely to be prescribed an antipsychotic than other age groups.

Source: Reference 5Our review suggests that a history of NMS is a risk factor for developing another episode. Twenty cases showed a clear history of NMS, and 2 cases reported 3 different NMS episodes in each patient.^19,21

In the cases we reviewed, NMS developed more often among men than women (Figure 2). The reason is not clear. One hypothesis suggests that men are more likely to present with severe agitation that requires aggressive antipsychotic treatment.^14,22

Figure 2
NMS: More common in men

Men may be at higher risk because they are more likely to present with severe agitation and receive larger doses of potent antipsychotics.

Source: References 14,22Previous reports suggested that parenteral antipsychotic administration might increase NMS risk. Most NMS cases in our review involved oral administration, perhaps because parenteral SGAs have become available only recently. In the future, increased use of parenteral SGAs might increase the incidence of NMS.

The NMS mortality rate associated with SGAs was lower than that linked to FGAs.⁶ This finding, however, may be influenced by increasing awareness of NMS among physicians, resulting in earlier diagnosis and treatment.⁶

Findings for specific SGAs

Aripiprazole. Because aripiprazole is the newest SGA, data on its association with NMS are limited. Our review looked at 2 cases. Both patients had atypical NMS features, including absence of fever and mild CPK elevation. In 1 case, aripiprazole was used to treat agitation in a 13-year-old girl with history of NMS. This resulted in a mild increase in tachycardia and brief worsening of serum CPK but did not significantly affect temperature, respiratory rate, or blood pressure.

Clozapine. Several NMS cases have been connected to clozapine monotherapy (6 cases) or combination therapy (22 cases). Compared with NMS caused by other antipsychotics, clozapine-induced NMS occurred sooner after patients started the drug or restarted it after discontinuation. NMS has developed in patients receiving chronic steady doses of clozapine, after dosage increases, and after other medications have been added.

Clozapine-treated patients need to be closely monitored for agranulocytosis symptoms, so any other adverse effects—such as initial symptoms of NMS—likely will be detected early. Some reports suggested that clozapine-induced NMS may feature fewer extrapyramidal side effects and a lower-than-typical increase in CPK. In the cases we reviewed, however, NMS presentations ranged from typical—with a highly elevated CPK—to mild with no rigidity and mild or no CPK elevation. Two of 28 cases reported neurologic sequelae, including severe truncal ataxia and dysmetria.

Clozapine has been used to treat patients with a history of NMS who experience psychotic relapse. In several cases, however, NMS recurred after clozapine was started. In 1 case, a third rechallenge with slow titration of clozapine was successful.

Olanzapine. Some studies have found olanzapine-induced NMS to be rare (rate ≤0.01%), but our review found 36 such cases. Ten patients (30%) had a history of NMS. Olanzapine dosing did not correlate with NMS—in 11 cases NMS occurred with daily doses ≤10 mg.

As with clozapine, the presentation of olanzapine-induced NMS varies widely. Onset from within 8 hours of starting olanzapine to after 2½ years of stable olanzapine dosing has been reported. Some cases have featured a typical NMS presentation. Atypical presentations have included:

• extremely elevated serum sodium
• absence of rigidity
• normal CPK
• generalized tonic-clonic seizures preceding NMS onset
• anterograde amnesia
• deficits in learning verbal information.

Olanzapine challenge for patients with a history of NMS often has triggered recurring NMS.

Quetiapine. NMS has been reported in patients receiving quetiapine monotherapy and combination therapy. Patients who previously experienced NMS after taking an FGA have developed quetiapine-induced NMS, as have some with a history of Lewy body disease. Two patients treated with quetiapine developed CPK elevations to almost 9,000 U/L (normal <171 U/L)—without other NMS features—that improved after discontinuing the medication.

Risperidone. NMS among patients taking risperidone occurs more frequently in those with history of NMS or who restart risperidone after discontinuation. Time to NMS occurrence after starting risperidone varies from hours to months. Atypical presentations include delayed fever, delayed muscle rigidity, massive intestinal bleeding, massive CPK elevation (such as 46,420 U/L), and hyponatremia instead of hypernatremia.

Ziprasidone. Administering IM ziprasidone or combining any form of the drug with other psychotropics increases NMS risk. Although most cases featured typical presentations, 1 case reported absence of muscle rigidity, which is present in >90% of patients with NMS associated with FGAs.

NMS sequelae related to SGAs

Brain injury following NMS can cause truncal ataxia, limb ataxia, athetosis, hemiballismus, dysmetria, dysarthria, sensory function problems, balance problems, persistent amnesia, difficulties comprehending commands, attention problems, and electroencephalograph or MRI abnormalities.^23,24 Postmortem studies of patients with NMS have revealed cerebellar degeneration, reduction of Purkinje and granule cells, and gliosis in the dentate nucleus.^25,26

Why some patients develop sequelae after NMS while others recover is unknown. Sustained hyperpyrexia, preexisting medical or neurologic disorders, polypharmacy, prolonged courses, and delayed diagnosis may play a role.^25-27

CASE CONTINUED: A complicated illness

Mrs. Z was diagnosed with NMS. Ziprasidone was discontinued, and supportive treatment, bromocriptine (2.5 mg po qid), and lorazepam (2 mg IV qid) were started. Temperatures of 101° to 103° F (38.3° to 39.4° C) persisted for the next 2 days. This hyperthermia was difficult to control because of suspected meningitis.

The team started ceftriaxone (2 gm IV q12h) while awaiting lumbar puncture results. CSF showed mild white blood cell elevation of 20/cu mm (normal 0 to 5/cu mm) with 62% neutrophils (normal 0 to 6%), normal protein, normal glucose, and negative cultures. After 2 days of antibiotic therapy, the patient developed diarrhea and was diagnosed with Clostridium difficile-associated colitis, a side effect of the antibiotic.

Treatment is mainly supportive

Recognizing NMS signs is the first and most important step to quick diagnosis and early medical intervention. Recommendations for medical treatment of NMS vary widely, but most stress stopping the triggering drug and initiating supportive care (Table 3).^27-29

Several medications have been used off-label to treat NMS based on anecdotal clinical reports. Benzodiazepines such as parenteral lorazepam, 1 to 2 mg every 6 to 8 hours, have been used to treat catatonic symptoms.³⁰ Dopamine agonists—including bromocriptine, 2.5 mg every 8 hours—have reduced the duration and mortality of NMS but have the potential to worsen psychotic symptoms and cause hypotension and emesis.³⁰

Table 3

Treating NMS: Where to start

CASE CONTINUED: Resuming antipsychotic Tx

Five days after intubation, Mrs. Z started to improve and was extubated successfully. However, she developed severe truncal ataxia, upper extremity tremors (resting and intentional), athetosis, hemiballismus, dysmetria, and dystonia. She continued to experience hallucinations after transfer back to the psychiatric floor.

Oral olanzapine challenge was started at 2.5 mg/d and titrated up to 10 mg/d over the next 7 days. Her psychotic symptoms showed mild improvement but her ataxic movements worsened and she fell frequently. Benztropine, 1 mg po bid, was added to her regimen and helped with the tremor. She was transferred for rehabilitation and eventually discharged home.

If a patient needs antipsychotics

If a patient who has experienced NMS continues to need pharmacotherapy for psychosis, wait 1 or 2 weeks after NMS symptoms resolve before restarting any antipsychotic.³¹ Although most patients can be treated safely with an antipsychotic after having NMS, clearly document the indications and your discussions with the patients and their families.

No conclusive evidence indicates which antipsychotic might lower a patient’s risk of recurrent NMS. Using an FGA in patients who recover from NMS carries a 30% risk of recurrent episodes.³ Data on the recurrence of NMS with SGAs are inconclusive. No relationship was found between relapse rate and patients’ age or sex.³²

Regardless of which drug you choose, start with a low dosage and titrate slowly. You also can protect patients by reducing risk factors for NMS, such as dehydration, and considering alternate therapies such as electroconvulsive therapy, when appropriate.

Related resources

• Neuroleptic Malignant Syndrome Information Service. http://nmsis.org.
• National Institute of Neurological Disorders and Stroke. Neuroleptic malignant syndrome information page www.ninds.nih.gov/disorders/neuroleptic_syndrome/neuroleptic_syndrome.htm.

Drug brand names

• Aripiprazole • Abilify
• Benztropine • Cogentin
• Bromocriptine • Parlodel
• Ceftriaxone • Rocephin
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosure

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

When second-generation antipsychotics (SGAs) were introduced, clinicians hoped the drugs would not have the potential to cause neuroleptic malignant syndrome (NMS).¹ Since then, however, case reports have made it clear that SGAs—like first-generation antipsychotics (FGAs)—can precipitate this life-threatening neurologic emergency.

To help you protect your patients receiving SGAs, this article explains how to:

• identify those at risk
• recognize the different NMS presentations associated with each SGA
• continue antipsychotic treatment for a patient with a history of NMS.

CASE STUDY: A drug-induced disorder

Mrs. Z, age 39, has a history of multiple hospitalizations for schizoaffective disorder complicated by poor compliance and a history of benzodiazepine abuse. This time she was admitted with increased auditory hallucinations and paranoid delusions of her family trying to poison her. Despite multiple haloperidol injections (5 mg IM q4h prn), Mrs. Z continued to have hallucinations and remained agitated.

Haloperidol was discontinued and ziprasidone (20 mg IM q4h prn) was started. After 3 days, Mrs. Z became less agitated and had fewer hallucinations. The IM route was discontinued and oral ziprasidone was started at 40 mg bid, then titrated to 80 mg bid after 2 days. On the third day after titration, Mrs. Z fell twice. She hit her head in one fall, but a brain CT to rule out bleeding was normal.

The next day, Mrs. Z became more confused and developed fever, tremor, urinary incontinence, and a severe headache. She became obtunded, was intubated, and was transferred to the intensive care unit of a tertiary care center.

On admission, her temperature was 103° F (39.4° C); she had severe muscle rigidity and blood pressure of 85/60 mm Hg. Creatine phosphokinase (CPK) was 2,559 U/L (normal 24 to 170 U/L). Liver enzymes were elevated: alanine transaminase was 202 U/L (normal 13 to 50 U/L), and aspartate transaminase (AST) was 190 U/L (normal 15 to 46 U/L). At 140 μg/dL, Mrs. Z’s serum iron was within normal limits (40 to 150 μg/dL).

Neuroleptic malignant syndrome

Clinical manifestations of NMS range from typical—as defined by the DSM-IV-TR (Table 1)^2,3—to atypical, without:

• fever⁴
• rigidity⁵
• CPK elevation.

Table 1

DSM-IV-TR definition of NMS*

Many conditions resemble NMS (Table 2). Because NMS can be fatal without emergent diagnosis and treatment, maintain a high index of suspicion for this condition whenever you prescribe antipsychotics.

Table 2

NMS differential diagnosis

NMS is believed to be caused by reduced dopamine activity in the brain associated with dopamine antagonists, interruptions in nigrostriatal dopamine pathways, or withdrawal of dopaminergic medications.³ However, dopamine D₂ receptor blocking potential is not directly linked to the occurrence of NMS.⁶ Other mechanisms include genetic susceptibility and different CNS neurotransmitter disturbances.⁷

NMS develops in an estimated 0.02% to 2.5% of patients treated with antipsychotics.^8-10 The syndrome appears to occur slightly less frequently with SGAs than with FGAs.^6,10

Risk factors. NMS can develop at any age, in men and women, and in patients with psychiatric or medical illness.^11,12 In addition to antipsychotics, other medications—including antiemetics and sedatives—can cause NMS. The syndrome has been triggered when Parkinson’s disease patients stop taking or reduce the dose of a dopamine agonist or switch from 1 dopamine agonist to another.^13,14

Symptoms usually develop during the first 2 weeks of pharmacotherapy but may start after the initial dose or during long-term stable therapy.¹⁵ Although some studies found NMS development to be dose-independent, multiple cases have demonstrated an association with dose changes. Death occurs from dysautonomic manifestations and systemic complications.

An elevated risk for NMS may exist in patients with:

• mood disorders
• preexisting catatonia¹⁶
• complicated medical and neurologic disorders, such as encephalitis or mental retardation¹⁷
• poor functional and physiologic status³
• concurrent lithium treatment
• IM injection of an antipsychotic
• use of a high-potency antipsychotic, such as haloperidol
• psychomotor agitation.

Other potential risk factors include dehydration, adolescent age, male gender, low serum iron concentrations, relatively high antipsychotic dosages, and mental retardation or prior structural brain injury.^18-20

NMS and SGAs

We reviewed 88 reports of NMS cases associated with 6 SGAs: olanzapine, clozapine, risperidone, ziprasidone, quetiapine, and aripiprazole. In this article, we cite representative cases only; readers interested in the full literature search can find this evidence and its references in the Case Reports Table.

NMS cases were fairly evenly distributed across all age groups (Figure 1). SGAs were implicated in NMS when used as monotherapy in 9 cases (10%) and in combination with other psychotropics in 41 cases (47%). We could not find medication regimen data for 38 cases (43%).

Figure 1
NMS incidence across age groups

Incidence is dispersed fairly evenly; elderly patients may be less likely to be prescribed an antipsychotic than other age groups.

Source: Reference 5Our review suggests that a history of NMS is a risk factor for developing another episode. Twenty cases showed a clear history of NMS, and 2 cases reported 3 different NMS episodes in each patient.^19,21

In the cases we reviewed, NMS developed more often among men than women (Figure 2). The reason is not clear. One hypothesis suggests that men are more likely to present with severe agitation that requires aggressive antipsychotic treatment.^14,22

Figure 2
NMS: More common in men

Men may be at higher risk because they are more likely to present with severe agitation and receive larger doses of potent antipsychotics.

Source: References 14,22Previous reports suggested that parenteral antipsychotic administration might increase NMS risk. Most NMS cases in our review involved oral administration, perhaps because parenteral SGAs have become available only recently. In the future, increased use of parenteral SGAs might increase the incidence of NMS.

The NMS mortality rate associated with SGAs was lower than that linked to FGAs.⁶ This finding, however, may be influenced by increasing awareness of NMS among physicians, resulting in earlier diagnosis and treatment.⁶

Findings for specific SGAs

Aripiprazole. Because aripiprazole is the newest SGA, data on its association with NMS are limited. Our review looked at 2 cases. Both patients had atypical NMS features, including absence of fever and mild CPK elevation. In 1 case, aripiprazole was used to treat agitation in a 13-year-old girl with history of NMS. This resulted in a mild increase in tachycardia and brief worsening of serum CPK but did not significantly affect temperature, respiratory rate, or blood pressure.

Clozapine. Several NMS cases have been connected to clozapine monotherapy (6 cases) or combination therapy (22 cases). Compared with NMS caused by other antipsychotics, clozapine-induced NMS occurred sooner after patients started the drug or restarted it after discontinuation. NMS has developed in patients receiving chronic steady doses of clozapine, after dosage increases, and after other medications have been added.

Clozapine-treated patients need to be closely monitored for agranulocytosis symptoms, so any other adverse effects—such as initial symptoms of NMS—likely will be detected early. Some reports suggested that clozapine-induced NMS may feature fewer extrapyramidal side effects and a lower-than-typical increase in CPK. In the cases we reviewed, however, NMS presentations ranged from typical—with a highly elevated CPK—to mild with no rigidity and mild or no CPK elevation. Two of 28 cases reported neurologic sequelae, including severe truncal ataxia and dysmetria.

Clozapine has been used to treat patients with a history of NMS who experience psychotic relapse. In several cases, however, NMS recurred after clozapine was started. In 1 case, a third rechallenge with slow titration of clozapine was successful.

Olanzapine. Some studies have found olanzapine-induced NMS to be rare (rate ≤0.01%), but our review found 36 such cases. Ten patients (30%) had a history of NMS. Olanzapine dosing did not correlate with NMS—in 11 cases NMS occurred with daily doses ≤10 mg.

As with clozapine, the presentation of olanzapine-induced NMS varies widely. Onset from within 8 hours of starting olanzapine to after 2½ years of stable olanzapine dosing has been reported. Some cases have featured a typical NMS presentation. Atypical presentations have included:

• extremely elevated serum sodium
• absence of rigidity
• normal CPK
• generalized tonic-clonic seizures preceding NMS onset
• anterograde amnesia
• deficits in learning verbal information.

Olanzapine challenge for patients with a history of NMS often has triggered recurring NMS.

Quetiapine. NMS has been reported in patients receiving quetiapine monotherapy and combination therapy. Patients who previously experienced NMS after taking an FGA have developed quetiapine-induced NMS, as have some with a history of Lewy body disease. Two patients treated with quetiapine developed CPK elevations to almost 9,000 U/L (normal <171 U/L)—without other NMS features—that improved after discontinuing the medication.

Risperidone. NMS among patients taking risperidone occurs more frequently in those with history of NMS or who restart risperidone after discontinuation. Time to NMS occurrence after starting risperidone varies from hours to months. Atypical presentations include delayed fever, delayed muscle rigidity, massive intestinal bleeding, massive CPK elevation (such as 46,420 U/L), and hyponatremia instead of hypernatremia.

Ziprasidone. Administering IM ziprasidone or combining any form of the drug with other psychotropics increases NMS risk. Although most cases featured typical presentations, 1 case reported absence of muscle rigidity, which is present in >90% of patients with NMS associated with FGAs.

NMS sequelae related to SGAs

Brain injury following NMS can cause truncal ataxia, limb ataxia, athetosis, hemiballismus, dysmetria, dysarthria, sensory function problems, balance problems, persistent amnesia, difficulties comprehending commands, attention problems, and electroencephalograph or MRI abnormalities.^23,24 Postmortem studies of patients with NMS have revealed cerebellar degeneration, reduction of Purkinje and granule cells, and gliosis in the dentate nucleus.^25,26

Why some patients develop sequelae after NMS while others recover is unknown. Sustained hyperpyrexia, preexisting medical or neurologic disorders, polypharmacy, prolonged courses, and delayed diagnosis may play a role.^25-27

CASE CONTINUED: A complicated illness

Mrs. Z was diagnosed with NMS. Ziprasidone was discontinued, and supportive treatment, bromocriptine (2.5 mg po qid), and lorazepam (2 mg IV qid) were started. Temperatures of 101° to 103° F (38.3° to 39.4° C) persisted for the next 2 days. This hyperthermia was difficult to control because of suspected meningitis.

The team started ceftriaxone (2 gm IV q12h) while awaiting lumbar puncture results. CSF showed mild white blood cell elevation of 20/cu mm (normal 0 to 5/cu mm) with 62% neutrophils (normal 0 to 6%), normal protein, normal glucose, and negative cultures. After 2 days of antibiotic therapy, the patient developed diarrhea and was diagnosed with Clostridium difficile-associated colitis, a side effect of the antibiotic.

Treatment is mainly supportive

Recognizing NMS signs is the first and most important step to quick diagnosis and early medical intervention. Recommendations for medical treatment of NMS vary widely, but most stress stopping the triggering drug and initiating supportive care (Table 3).^27-29

Several medications have been used off-label to treat NMS based on anecdotal clinical reports. Benzodiazepines such as parenteral lorazepam, 1 to 2 mg every 6 to 8 hours, have been used to treat catatonic symptoms.³⁰ Dopamine agonists—including bromocriptine, 2.5 mg every 8 hours—have reduced the duration and mortality of NMS but have the potential to worsen psychotic symptoms and cause hypotension and emesis.³⁰

Table 3

Treating NMS: Where to start

CASE CONTINUED: Resuming antipsychotic Tx

Five days after intubation, Mrs. Z started to improve and was extubated successfully. However, she developed severe truncal ataxia, upper extremity tremors (resting and intentional), athetosis, hemiballismus, dysmetria, and dystonia. She continued to experience hallucinations after transfer back to the psychiatric floor.

Oral olanzapine challenge was started at 2.5 mg/d and titrated up to 10 mg/d over the next 7 days. Her psychotic symptoms showed mild improvement but her ataxic movements worsened and she fell frequently. Benztropine, 1 mg po bid, was added to her regimen and helped with the tremor. She was transferred for rehabilitation and eventually discharged home.

If a patient needs antipsychotics

If a patient who has experienced NMS continues to need pharmacotherapy for psychosis, wait 1 or 2 weeks after NMS symptoms resolve before restarting any antipsychotic.³¹ Although most patients can be treated safely with an antipsychotic after having NMS, clearly document the indications and your discussions with the patients and their families.

No conclusive evidence indicates which antipsychotic might lower a patient’s risk of recurrent NMS. Using an FGA in patients who recover from NMS carries a 30% risk of recurrent episodes.³ Data on the recurrence of NMS with SGAs are inconclusive. No relationship was found between relapse rate and patients’ age or sex.³²

Regardless of which drug you choose, start with a low dosage and titrate slowly. You also can protect patients by reducing risk factors for NMS, such as dehydration, and considering alternate therapies such as electroconvulsive therapy, when appropriate.

Related resources

• Neuroleptic Malignant Syndrome Information Service. http://nmsis.org.
• National Institute of Neurological Disorders and Stroke. Neuroleptic malignant syndrome information page www.ninds.nih.gov/disorders/neuroleptic_syndrome/neuroleptic_syndrome.htm.

Drug brand names

• Aripiprazole • Abilify
• Benztropine • Cogentin
• Bromocriptine • Parlodel
• Ceftriaxone • Rocephin
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosure

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

When second-generation antipsychotics (SGAs) were introduced, clinicians hoped the drugs would not have the potential to cause neuroleptic malignant syndrome (NMS).¹ Since then, however, case reports have made it clear that SGAs—like first-generation antipsychotics (FGAs)—can precipitate this life-threatening neurologic emergency.

To help you protect your patients receiving SGAs, this article explains how to:

• identify those at risk
• recognize the different NMS presentations associated with each SGA
• continue antipsychotic treatment for a patient with a history of NMS.

CASE STUDY: A drug-induced disorder

Mrs. Z, age 39, has a history of multiple hospitalizations for schizoaffective disorder complicated by poor compliance and a history of benzodiazepine abuse. This time she was admitted with increased auditory hallucinations and paranoid delusions of her family trying to poison her. Despite multiple haloperidol injections (5 mg IM q4h prn), Mrs. Z continued to have hallucinations and remained agitated.

Haloperidol was discontinued and ziprasidone (20 mg IM q4h prn) was started. After 3 days, Mrs. Z became less agitated and had fewer hallucinations. The IM route was discontinued and oral ziprasidone was started at 40 mg bid, then titrated to 80 mg bid after 2 days. On the third day after titration, Mrs. Z fell twice. She hit her head in one fall, but a brain CT to rule out bleeding was normal.

The next day, Mrs. Z became more confused and developed fever, tremor, urinary incontinence, and a severe headache. She became obtunded, was intubated, and was transferred to the intensive care unit of a tertiary care center.

On admission, her temperature was 103° F (39.4° C); she had severe muscle rigidity and blood pressure of 85/60 mm Hg. Creatine phosphokinase (CPK) was 2,559 U/L (normal 24 to 170 U/L). Liver enzymes were elevated: alanine transaminase was 202 U/L (normal 13 to 50 U/L), and aspartate transaminase (AST) was 190 U/L (normal 15 to 46 U/L). At 140 μg/dL, Mrs. Z’s serum iron was within normal limits (40 to 150 μg/dL).

Neuroleptic malignant syndrome

Clinical manifestations of NMS range from typical—as defined by the DSM-IV-TR (Table 1)^2,3—to atypical, without:

• fever⁴
• rigidity⁵
• CPK elevation.

Table 1

DSM-IV-TR definition of NMS*

Many conditions resemble NMS (Table 2). Because NMS can be fatal without emergent diagnosis and treatment, maintain a high index of suspicion for this condition whenever you prescribe antipsychotics.

Table 2

NMS differential diagnosis

NMS is believed to be caused by reduced dopamine activity in the brain associated with dopamine antagonists, interruptions in nigrostriatal dopamine pathways, or withdrawal of dopaminergic medications.³ However, dopamine D₂ receptor blocking potential is not directly linked to the occurrence of NMS.⁶ Other mechanisms include genetic susceptibility and different CNS neurotransmitter disturbances.⁷

NMS develops in an estimated 0.02% to 2.5% of patients treated with antipsychotics.^8-10 The syndrome appears to occur slightly less frequently with SGAs than with FGAs.^6,10

Risk factors. NMS can develop at any age, in men and women, and in patients with psychiatric or medical illness.^11,12 In addition to antipsychotics, other medications—including antiemetics and sedatives—can cause NMS. The syndrome has been triggered when Parkinson’s disease patients stop taking or reduce the dose of a dopamine agonist or switch from 1 dopamine agonist to another.^13,14

Symptoms usually develop during the first 2 weeks of pharmacotherapy but may start after the initial dose or during long-term stable therapy.¹⁵ Although some studies found NMS development to be dose-independent, multiple cases have demonstrated an association with dose changes. Death occurs from dysautonomic manifestations and systemic complications.

An elevated risk for NMS may exist in patients with:

• mood disorders
• preexisting catatonia¹⁶
• complicated medical and neurologic disorders, such as encephalitis or mental retardation¹⁷
• poor functional and physiologic status³
• concurrent lithium treatment
• IM injection of an antipsychotic
• use of a high-potency antipsychotic, such as haloperidol
• psychomotor agitation.

Other potential risk factors include dehydration, adolescent age, male gender, low serum iron concentrations, relatively high antipsychotic dosages, and mental retardation or prior structural brain injury.^18-20

NMS and SGAs

We reviewed 88 reports of NMS cases associated with 6 SGAs: olanzapine, clozapine, risperidone, ziprasidone, quetiapine, and aripiprazole. In this article, we cite representative cases only; readers interested in the full literature search can find this evidence and its references in the Case Reports Table.

NMS cases were fairly evenly distributed across all age groups (Figure 1). SGAs were implicated in NMS when used as monotherapy in 9 cases (10%) and in combination with other psychotropics in 41 cases (47%). We could not find medication regimen data for 38 cases (43%).

Figure 1
NMS incidence across age groups

Incidence is dispersed fairly evenly; elderly patients may be less likely to be prescribed an antipsychotic than other age groups.

Source: Reference 5Our review suggests that a history of NMS is a risk factor for developing another episode. Twenty cases showed a clear history of NMS, and 2 cases reported 3 different NMS episodes in each patient.^19,21

In the cases we reviewed, NMS developed more often among men than women (Figure 2). The reason is not clear. One hypothesis suggests that men are more likely to present with severe agitation that requires aggressive antipsychotic treatment.^14,22

Figure 2
NMS: More common in men

Men may be at higher risk because they are more likely to present with severe agitation and receive larger doses of potent antipsychotics.

Source: References 14,22Previous reports suggested that parenteral antipsychotic administration might increase NMS risk. Most NMS cases in our review involved oral administration, perhaps because parenteral SGAs have become available only recently. In the future, increased use of parenteral SGAs might increase the incidence of NMS.

The NMS mortality rate associated with SGAs was lower than that linked to FGAs.⁶ This finding, however, may be influenced by increasing awareness of NMS among physicians, resulting in earlier diagnosis and treatment.⁶

Findings for specific SGAs

Aripiprazole. Because aripiprazole is the newest SGA, data on its association with NMS are limited. Our review looked at 2 cases. Both patients had atypical NMS features, including absence of fever and mild CPK elevation. In 1 case, aripiprazole was used to treat agitation in a 13-year-old girl with history of NMS. This resulted in a mild increase in tachycardia and brief worsening of serum CPK but did not significantly affect temperature, respiratory rate, or blood pressure.

Clozapine. Several NMS cases have been connected to clozapine monotherapy (6 cases) or combination therapy (22 cases). Compared with NMS caused by other antipsychotics, clozapine-induced NMS occurred sooner after patients started the drug or restarted it after discontinuation. NMS has developed in patients receiving chronic steady doses of clozapine, after dosage increases, and after other medications have been added.

Clozapine-treated patients need to be closely monitored for agranulocytosis symptoms, so any other adverse effects—such as initial symptoms of NMS—likely will be detected early. Some reports suggested that clozapine-induced NMS may feature fewer extrapyramidal side effects and a lower-than-typical increase in CPK. In the cases we reviewed, however, NMS presentations ranged from typical—with a highly elevated CPK—to mild with no rigidity and mild or no CPK elevation. Two of 28 cases reported neurologic sequelae, including severe truncal ataxia and dysmetria.

Clozapine has been used to treat patients with a history of NMS who experience psychotic relapse. In several cases, however, NMS recurred after clozapine was started. In 1 case, a third rechallenge with slow titration of clozapine was successful.

Olanzapine. Some studies have found olanzapine-induced NMS to be rare (rate ≤0.01%), but our review found 36 such cases. Ten patients (30%) had a history of NMS. Olanzapine dosing did not correlate with NMS—in 11 cases NMS occurred with daily doses ≤10 mg.

As with clozapine, the presentation of olanzapine-induced NMS varies widely. Onset from within 8 hours of starting olanzapine to after 2½ years of stable olanzapine dosing has been reported. Some cases have featured a typical NMS presentation. Atypical presentations have included:

• extremely elevated serum sodium
• absence of rigidity
• normal CPK
• generalized tonic-clonic seizures preceding NMS onset
• anterograde amnesia
• deficits in learning verbal information.

Olanzapine challenge for patients with a history of NMS often has triggered recurring NMS.

Quetiapine. NMS has been reported in patients receiving quetiapine monotherapy and combination therapy. Patients who previously experienced NMS after taking an FGA have developed quetiapine-induced NMS, as have some with a history of Lewy body disease. Two patients treated with quetiapine developed CPK elevations to almost 9,000 U/L (normal <171 U/L)—without other NMS features—that improved after discontinuing the medication.

Risperidone. NMS among patients taking risperidone occurs more frequently in those with history of NMS or who restart risperidone after discontinuation. Time to NMS occurrence after starting risperidone varies from hours to months. Atypical presentations include delayed fever, delayed muscle rigidity, massive intestinal bleeding, massive CPK elevation (such as 46,420 U/L), and hyponatremia instead of hypernatremia.

Ziprasidone. Administering IM ziprasidone or combining any form of the drug with other psychotropics increases NMS risk. Although most cases featured typical presentations, 1 case reported absence of muscle rigidity, which is present in >90% of patients with NMS associated with FGAs.

NMS sequelae related to SGAs

Brain injury following NMS can cause truncal ataxia, limb ataxia, athetosis, hemiballismus, dysmetria, dysarthria, sensory function problems, balance problems, persistent amnesia, difficulties comprehending commands, attention problems, and electroencephalograph or MRI abnormalities.^23,24 Postmortem studies of patients with NMS have revealed cerebellar degeneration, reduction of Purkinje and granule cells, and gliosis in the dentate nucleus.^25,26

Why some patients develop sequelae after NMS while others recover is unknown. Sustained hyperpyrexia, preexisting medical or neurologic disorders, polypharmacy, prolonged courses, and delayed diagnosis may play a role.^25-27

CASE CONTINUED: A complicated illness

Mrs. Z was diagnosed with NMS. Ziprasidone was discontinued, and supportive treatment, bromocriptine (2.5 mg po qid), and lorazepam (2 mg IV qid) were started. Temperatures of 101° to 103° F (38.3° to 39.4° C) persisted for the next 2 days. This hyperthermia was difficult to control because of suspected meningitis.

The team started ceftriaxone (2 gm IV q12h) while awaiting lumbar puncture results. CSF showed mild white blood cell elevation of 20/cu mm (normal 0 to 5/cu mm) with 62% neutrophils (normal 0 to 6%), normal protein, normal glucose, and negative cultures. After 2 days of antibiotic therapy, the patient developed diarrhea and was diagnosed with Clostridium difficile-associated colitis, a side effect of the antibiotic.

Treatment is mainly supportive

Recognizing NMS signs is the first and most important step to quick diagnosis and early medical intervention. Recommendations for medical treatment of NMS vary widely, but most stress stopping the triggering drug and initiating supportive care (Table 3).^27-29

Several medications have been used off-label to treat NMS based on anecdotal clinical reports. Benzodiazepines such as parenteral lorazepam, 1 to 2 mg every 6 to 8 hours, have been used to treat catatonic symptoms.³⁰ Dopamine agonists—including bromocriptine, 2.5 mg every 8 hours—have reduced the duration and mortality of NMS but have the potential to worsen psychotic symptoms and cause hypotension and emesis.³⁰

Table 3

Treating NMS: Where to start

CASE CONTINUED: Resuming antipsychotic Tx

Five days after intubation, Mrs. Z started to improve and was extubated successfully. However, she developed severe truncal ataxia, upper extremity tremors (resting and intentional), athetosis, hemiballismus, dysmetria, and dystonia. She continued to experience hallucinations after transfer back to the psychiatric floor.

Oral olanzapine challenge was started at 2.5 mg/d and titrated up to 10 mg/d over the next 7 days. Her psychotic symptoms showed mild improvement but her ataxic movements worsened and she fell frequently. Benztropine, 1 mg po bid, was added to her regimen and helped with the tremor. She was transferred for rehabilitation and eventually discharged home.

If a patient needs antipsychotics

If a patient who has experienced NMS continues to need pharmacotherapy for psychosis, wait 1 or 2 weeks after NMS symptoms resolve before restarting any antipsychotic.³¹ Although most patients can be treated safely with an antipsychotic after having NMS, clearly document the indications and your discussions with the patients and their families.

No conclusive evidence indicates which antipsychotic might lower a patient’s risk of recurrent NMS. Using an FGA in patients who recover from NMS carries a 30% risk of recurrent episodes.³ Data on the recurrence of NMS with SGAs are inconclusive. No relationship was found between relapse rate and patients’ age or sex.³²

Regardless of which drug you choose, start with a low dosage and titrate slowly. You also can protect patients by reducing risk factors for NMS, such as dehydration, and considering alternate therapies such as electroconvulsive therapy, when appropriate.

Related resources

• Neuroleptic Malignant Syndrome Information Service. http://nmsis.org.
• National Institute of Neurological Disorders and Stroke. Neuroleptic malignant syndrome information page www.ninds.nih.gov/disorders/neuroleptic_syndrome/neuroleptic_syndrome.htm.

Drug brand names

• Aripiprazole • Abilify
• Benztropine • Cogentin
• Bromocriptine • Parlodel
• Ceftriaxone • Rocephin
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Disclosure

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

Patients with borderline personality disorder (BPD) exhibit a pattern of instability in interpersonal relation-ships, self-image, and affects, and marked impulsivity beginning in early adulthood.¹ These patients may experience other symptoms, such as mood swings or transient psychotic episodes, that are exacerbated by stress.

A BPD patient likely has additional diagnoses from previous clinicians—such as bipolar disorder, dysthymic disorder, panic disorder, major recurrent depression, substance abuse, posttraumatic stress disorder, intermittent explosive disorder, or any variety of adjustment, anxiety, eating, impulse control, mood, somatoform, or personality disorders.² However, a BPD diagnosis best describes many of these patients, and the mnemonic “DARE” enumerates the most commonly encountered clinical picture.

Depression, Destruction, Denial. Chronic low-grade depression is the baseline mood for BPD. The patients might not report suicidal ideation or might deny a desire to die. But the predilection and potential for risky behavior that could result in accidental injury or death tends to confirm the presence of an underlying self-destructive wish.

Anger, Abandonment, Abuse. Typically, BPD patients are angry at the world. Anger simmers just below the threshold of self-control. When it boils over, BPD patients are apt to take their anger out on themselves by committing suicide or a self-mutilative act, or on others with passive aggression or the kind of physical or emotional abuse they themselves suffered.

BPD patients’ histories often include physical or emotional abandonment or abuse.

Relationships, Regrets, Repetition. Repeated patterns of unstable relationships are characteristic. Often BPD patients have multiple romantic partners, frequent job turnover, interrupted education, and few long-term, mature friendships. These patients’ friends and partners frequently suffer from similar problematic personality characteristics. BPD patients seem unable to break free of their unsuccessful patterns and repeatedly fail to maintain healthy, productive relationships.

Extremes, Emergencies, Ennui. Overuse of prescription drugs, alcohol, or other substances result in frequent emergency room visits. Bulimia, sexual promiscuity, and multiple body piercings or tattoos are emblematic of BPD. Ennui—a feeling of weariness or discontent—is fought off by engaging in extreme behaviors, such as reckless driving.

Many BPD patients improve and show greater stability in jobs and relationships with therapeutic intervention, although they often have a lifelong tendency toward impulsivity and intense relationships and emotions.

Dr. Roth is attending psychiatrist, Department of Veterans Affairs Medical Center, North Chicago, IL.

Patients with borderline personality disorder (BPD) exhibit a pattern of instability in interpersonal relation-ships, self-image, and affects, and marked impulsivity beginning in early adulthood.¹ These patients may experience other symptoms, such as mood swings or transient psychotic episodes, that are exacerbated by stress.

A BPD patient likely has additional diagnoses from previous clinicians—such as bipolar disorder, dysthymic disorder, panic disorder, major recurrent depression, substance abuse, posttraumatic stress disorder, intermittent explosive disorder, or any variety of adjustment, anxiety, eating, impulse control, mood, somatoform, or personality disorders.² However, a BPD diagnosis best describes many of these patients, and the mnemonic “DARE” enumerates the most commonly encountered clinical picture.

Depression, Destruction, Denial. Chronic low-grade depression is the baseline mood for BPD. The patients might not report suicidal ideation or might deny a desire to die. But the predilection and potential for risky behavior that could result in accidental injury or death tends to confirm the presence of an underlying self-destructive wish.

Anger, Abandonment, Abuse. Typically, BPD patients are angry at the world. Anger simmers just below the threshold of self-control. When it boils over, BPD patients are apt to take their anger out on themselves by committing suicide or a self-mutilative act, or on others with passive aggression or the kind of physical or emotional abuse they themselves suffered.

BPD patients’ histories often include physical or emotional abandonment or abuse.

Relationships, Regrets, Repetition. Repeated patterns of unstable relationships are characteristic. Often BPD patients have multiple romantic partners, frequent job turnover, interrupted education, and few long-term, mature friendships. These patients’ friends and partners frequently suffer from similar problematic personality characteristics. BPD patients seem unable to break free of their unsuccessful patterns and repeatedly fail to maintain healthy, productive relationships.

Extremes, Emergencies, Ennui. Overuse of prescription drugs, alcohol, or other substances result in frequent emergency room visits. Bulimia, sexual promiscuity, and multiple body piercings or tattoos are emblematic of BPD. Ennui—a feeling of weariness or discontent—is fought off by engaging in extreme behaviors, such as reckless driving.

Many BPD patients improve and show greater stability in jobs and relationships with therapeutic intervention, although they often have a lifelong tendency toward impulsivity and intense relationships and emotions.

Dr. Roth is attending psychiatrist, Department of Veterans Affairs Medical Center, North Chicago, IL.

Patients with borderline personality disorder (BPD) exhibit a pattern of instability in interpersonal relation-ships, self-image, and affects, and marked impulsivity beginning in early adulthood.¹ These patients may experience other symptoms, such as mood swings or transient psychotic episodes, that are exacerbated by stress.

A BPD patient likely has additional diagnoses from previous clinicians—such as bipolar disorder, dysthymic disorder, panic disorder, major recurrent depression, substance abuse, posttraumatic stress disorder, intermittent explosive disorder, or any variety of adjustment, anxiety, eating, impulse control, mood, somatoform, or personality disorders.² However, a BPD diagnosis best describes many of these patients, and the mnemonic “DARE” enumerates the most commonly encountered clinical picture.

Depression, Destruction, Denial. Chronic low-grade depression is the baseline mood for BPD. The patients might not report suicidal ideation or might deny a desire to die. But the predilection and potential for risky behavior that could result in accidental injury or death tends to confirm the presence of an underlying self-destructive wish.

Anger, Abandonment, Abuse. Typically, BPD patients are angry at the world. Anger simmers just below the threshold of self-control. When it boils over, BPD patients are apt to take their anger out on themselves by committing suicide or a self-mutilative act, or on others with passive aggression or the kind of physical or emotional abuse they themselves suffered.

BPD patients’ histories often include physical or emotional abandonment or abuse.

Relationships, Regrets, Repetition. Repeated patterns of unstable relationships are characteristic. Often BPD patients have multiple romantic partners, frequent job turnover, interrupted education, and few long-term, mature friendships. These patients’ friends and partners frequently suffer from similar problematic personality characteristics. BPD patients seem unable to break free of their unsuccessful patterns and repeatedly fail to maintain healthy, productive relationships.

Extremes, Emergencies, Ennui. Overuse of prescription drugs, alcohol, or other substances result in frequent emergency room visits. Bulimia, sexual promiscuity, and multiple body piercings or tattoos are emblematic of BPD. Ennui—a feeling of weariness or discontent—is fought off by engaging in extreme behaviors, such as reckless driving.

Many BPD patients improve and show greater stability in jobs and relationships with therapeutic intervention, although they often have a lifelong tendency toward impulsivity and intense relationships and emotions.

Dr. Roth is attending psychiatrist, Department of Veterans Affairs Medical Center, North Chicago, IL.