Current Psychiatry

With the rapid emergence of novel therapies, psychiatrists face the challenge of deciphering the clinical application of published clinical trials. Although double-blind, randomized, placebo-controlled trials are the gold standard, their validity should be carefully examined.¹ The FRISBEE mnemonic from Duke University’s psychiatry residency program can help you incorporate evidence-based medicine into your patient care.

Follow-up. Carefully interpret studies with inadequate follow-up or high drop-out rates. The reason for patient discontinuation might not be related to the studied intervention.

Randomization. To control for unknown confounding variables, patient assignment must be randomized.

Intent-to-treat analysis. ITT assumes that complete data are available during final analysis on every subject, but subjects often drop out. To compensate for drop-outs, researchers could:

• carry forward the last available measurement as the final result, known as last observation carried forward (LOCF).
  
• use data only from patients who complete entire study protocol (completer analysis method).
  

Both methods have statistical limitations, but LOCF generally is preferred because it accounts for every subject who enrolled in the study.²

Similar baseline. Compare known characteristics of the treatment and placebo groups at baseline. Confounding variables, such as illness severity or medical or psychiatric comorbidities, should appear equally among randomized patient groups. Not all variables will be similar because of random effects, however.

Blinding. With ineffective blinding, patients or researchers can tell which treatment was administered. If this occurs, the study’s outcome likely is biased by treatment expectations. To detect faulty blinding, some studies ask patients and/or providers if they can guess the intervention that was delivered.

Equal treatment. Even with proper randomization and blinding, other intervention-related treatments—such as blood work to monitor side effects or the duration or frequency of provider contact—might not be administered equally among patient groups. This can clue patients and researchers into which intervention was administered and create bias.

Equivalence to your patient. A typical study patient often has few medical and psychiatric comorbidities or psychosocial risk factors. Your patient might be substantially different. Carefully compare the patients in the study with the patient in your office before choosing a treatment.

With the rapid emergence of novel therapies, psychiatrists face the challenge of deciphering the clinical application of published clinical trials. Although double-blind, randomized, placebo-controlled trials are the gold standard, their validity should be carefully examined.¹ The FRISBEE mnemonic from Duke University’s psychiatry residency program can help you incorporate evidence-based medicine into your patient care.

Follow-up. Carefully interpret studies with inadequate follow-up or high drop-out rates. The reason for patient discontinuation might not be related to the studied intervention.

Randomization. To control for unknown confounding variables, patient assignment must be randomized.

Intent-to-treat analysis. ITT assumes that complete data are available during final analysis on every subject, but subjects often drop out. To compensate for drop-outs, researchers could:

• carry forward the last available measurement as the final result, known as last observation carried forward (LOCF).
  
• use data only from patients who complete entire study protocol (completer analysis method).
  

Both methods have statistical limitations, but LOCF generally is preferred because it accounts for every subject who enrolled in the study.²

Similar baseline. Compare known characteristics of the treatment and placebo groups at baseline. Confounding variables, such as illness severity or medical or psychiatric comorbidities, should appear equally among randomized patient groups. Not all variables will be similar because of random effects, however.

Blinding. With ineffective blinding, patients or researchers can tell which treatment was administered. If this occurs, the study’s outcome likely is biased by treatment expectations. To detect faulty blinding, some studies ask patients and/or providers if they can guess the intervention that was delivered.

Equal treatment. Even with proper randomization and blinding, other intervention-related treatments—such as blood work to monitor side effects or the duration or frequency of provider contact—might not be administered equally among patient groups. This can clue patients and researchers into which intervention was administered and create bias.

Equivalence to your patient. A typical study patient often has few medical and psychiatric comorbidities or psychosocial risk factors. Your patient might be substantially different. Carefully compare the patients in the study with the patient in your office before choosing a treatment.

With the rapid emergence of novel therapies, psychiatrists face the challenge of deciphering the clinical application of published clinical trials. Although double-blind, randomized, placebo-controlled trials are the gold standard, their validity should be carefully examined.¹ The FRISBEE mnemonic from Duke University’s psychiatry residency program can help you incorporate evidence-based medicine into your patient care.

Follow-up. Carefully interpret studies with inadequate follow-up or high drop-out rates. The reason for patient discontinuation might not be related to the studied intervention.

Randomization. To control for unknown confounding variables, patient assignment must be randomized.

Intent-to-treat analysis. ITT assumes that complete data are available during final analysis on every subject, but subjects often drop out. To compensate for drop-outs, researchers could:

• carry forward the last available measurement as the final result, known as last observation carried forward (LOCF).
  
• use data only from patients who complete entire study protocol (completer analysis method).
  

Both methods have statistical limitations, but LOCF generally is preferred because it accounts for every subject who enrolled in the study.²

Similar baseline. Compare known characteristics of the treatment and placebo groups at baseline. Confounding variables, such as illness severity or medical or psychiatric comorbidities, should appear equally among randomized patient groups. Not all variables will be similar because of random effects, however.

Blinding. With ineffective blinding, patients or researchers can tell which treatment was administered. If this occurs, the study’s outcome likely is biased by treatment expectations. To detect faulty blinding, some studies ask patients and/or providers if they can guess the intervention that was delivered.

Equal treatment. Even with proper randomization and blinding, other intervention-related treatments—such as blood work to monitor side effects or the duration or frequency of provider contact—might not be administered equally among patient groups. This can clue patients and researchers into which intervention was administered and create bias.

Equivalence to your patient. A typical study patient often has few medical and psychiatric comorbidities or psychosocial risk factors. Your patient might be substantially different. Carefully compare the patients in the study with the patient in your office before choosing a treatment.

Patients’ failure to keep appointments is a common problem. On average, patients miss approximately 15% of follow-up psychiatric appointments,¹ but the percentage is much higher in some patient populations, such as patients with significant socioeconomic difficulties. Those who miss appointments often have worse outcomes and even a higher likelihood of psychiatric readmission.²

We present strategies to help patients keep appointments and to handle occasional and repeated absences. Although the problem of missed appointments will never go away, following these suggestions could help minimize it.

Prevent the problem

Explain to the patient why regular appointments are important. The most important point is that clinician and patient must agree that—to best help the patient—treatment requires that all appointments be kept, barring emergencies.

Communicate clearly. Avoid emphasizing rules, such as that patients must keep 80% of appointments, give 48-hours’ notice for cancellations, or pay a no-show fee. These suggest that patients may miss appointments as long as they follow the rules.

Fix structural problems in your practice that may be barriers to making, rescheduling, or cancelling appointments. Be clear with patients about:

• the phone number they should call for appointments
  
• if they or you must cancel, that person is to reschedule at the earliest opportunity.
  

If the patient is missing appointments because the frequency is too burdensome, in many cases less frequent but more regular visits may be better.

During your early sessions with patients, be sure they understand that you reserve specific times for them. Make sure, however, that patients don’t interpret this to mean that attending every appointment is for your benefit, rather than important for their treatment.

Emphasize responsibility. At the end of each session, set a goal with patients for the next appointment. With a patient who has missed appointments, ask for a commitment that he or she will come to the next session. We have found that stating that you are concerned the patient might not come to the next session can paradoxically be helpful.

Having your receptionist call and remind patients the day before their visits might not be a good idea in many cases. Patients might think these calls relieve them of the responsibility for remembering to keep appointments.

With patients you think might miss appointments—especially those on a medication that requires careful monitoring—consider writing prescriptions to last no longer than the next appointment.

Occasional missed appointments

Don’t just let it go when patients occasionally miss appointments without adequate reason. Ignoring the problem lets it progress.

Resist the temptation to be courteous and say, “That’s all right” when patients apologize or give a reason for missing the session. Doing so gives a subtle message that missing appointments is acceptable.

Discussing the patients’ reasons for missing appointments might solve the problem at times. For example, patients might not mention transportation or child care problems.

Note in the chart when a patient does not come to an appointment so you can calculate how many have been missed. This notation also will remind you to address these missed appointments during the next visit. Because discussing missed appointments at the start of the session might seem confrontational or punitive, inquire about the reasons for missing the previous appointment in a gentle manner and later in the session.

Remind patients that therapy is the tool to solve their emotional problems and thus has a special place in their lives. If patients want to solve other problems, they must start by regularly attending therapy.

Repeatedly missed appointments

When a patient misses appointments repeatedly, take 1 or more sessions to discuss it. This has to be done before therapy can proceed effectively (of course you might need to postpone this discussion if the patient has experienced major stressful events or has other pressing clinical issues).

When doing this, resist the temptation to become sidetracked by other issues the patient brings up. You can let the patient vent for a few minutes, but don’t let most of the session go by before addressing the missed appointments.

Patients’ failure to keep appointments is a common problem. On average, patients miss approximately 15% of follow-up psychiatric appointments,¹ but the percentage is much higher in some patient populations, such as patients with significant socioeconomic difficulties. Those who miss appointments often have worse outcomes and even a higher likelihood of psychiatric readmission.²

We present strategies to help patients keep appointments and to handle occasional and repeated absences. Although the problem of missed appointments will never go away, following these suggestions could help minimize it.

Prevent the problem

Explain to the patient why regular appointments are important. The most important point is that clinician and patient must agree that—to best help the patient—treatment requires that all appointments be kept, barring emergencies.

Communicate clearly. Avoid emphasizing rules, such as that patients must keep 80% of appointments, give 48-hours’ notice for cancellations, or pay a no-show fee. These suggest that patients may miss appointments as long as they follow the rules.

Fix structural problems in your practice that may be barriers to making, rescheduling, or cancelling appointments. Be clear with patients about:

• the phone number they should call for appointments
  
• if they or you must cancel, that person is to reschedule at the earliest opportunity.
  

If the patient is missing appointments because the frequency is too burdensome, in many cases less frequent but more regular visits may be better.

During your early sessions with patients, be sure they understand that you reserve specific times for them. Make sure, however, that patients don’t interpret this to mean that attending every appointment is for your benefit, rather than important for their treatment.

Emphasize responsibility. At the end of each session, set a goal with patients for the next appointment. With a patient who has missed appointments, ask for a commitment that he or she will come to the next session. We have found that stating that you are concerned the patient might not come to the next session can paradoxically be helpful.

Having your receptionist call and remind patients the day before their visits might not be a good idea in many cases. Patients might think these calls relieve them of the responsibility for remembering to keep appointments.

With patients you think might miss appointments—especially those on a medication that requires careful monitoring—consider writing prescriptions to last no longer than the next appointment.

Occasional missed appointments

Don’t just let it go when patients occasionally miss appointments without adequate reason. Ignoring the problem lets it progress.

Resist the temptation to be courteous and say, “That’s all right” when patients apologize or give a reason for missing the session. Doing so gives a subtle message that missing appointments is acceptable.

Discussing the patients’ reasons for missing appointments might solve the problem at times. For example, patients might not mention transportation or child care problems.

Note in the chart when a patient does not come to an appointment so you can calculate how many have been missed. This notation also will remind you to address these missed appointments during the next visit. Because discussing missed appointments at the start of the session might seem confrontational or punitive, inquire about the reasons for missing the previous appointment in a gentle manner and later in the session.

Remind patients that therapy is the tool to solve their emotional problems and thus has a special place in their lives. If patients want to solve other problems, they must start by regularly attending therapy.

Repeatedly missed appointments

When a patient misses appointments repeatedly, take 1 or more sessions to discuss it. This has to be done before therapy can proceed effectively (of course you might need to postpone this discussion if the patient has experienced major stressful events or has other pressing clinical issues).

When doing this, resist the temptation to become sidetracked by other issues the patient brings up. You can let the patient vent for a few minutes, but don’t let most of the session go by before addressing the missed appointments.

Patients’ failure to keep appointments is a common problem. On average, patients miss approximately 15% of follow-up psychiatric appointments,¹ but the percentage is much higher in some patient populations, such as patients with significant socioeconomic difficulties. Those who miss appointments often have worse outcomes and even a higher likelihood of psychiatric readmission.²

We present strategies to help patients keep appointments and to handle occasional and repeated absences. Although the problem of missed appointments will never go away, following these suggestions could help minimize it.

Prevent the problem

Explain to the patient why regular appointments are important. The most important point is that clinician and patient must agree that—to best help the patient—treatment requires that all appointments be kept, barring emergencies.

Communicate clearly. Avoid emphasizing rules, such as that patients must keep 80% of appointments, give 48-hours’ notice for cancellations, or pay a no-show fee. These suggest that patients may miss appointments as long as they follow the rules.

Fix structural problems in your practice that may be barriers to making, rescheduling, or cancelling appointments. Be clear with patients about:

• the phone number they should call for appointments
  
• if they or you must cancel, that person is to reschedule at the earliest opportunity.
  

If the patient is missing appointments because the frequency is too burdensome, in many cases less frequent but more regular visits may be better.

During your early sessions with patients, be sure they understand that you reserve specific times for them. Make sure, however, that patients don’t interpret this to mean that attending every appointment is for your benefit, rather than important for their treatment.

Emphasize responsibility. At the end of each session, set a goal with patients for the next appointment. With a patient who has missed appointments, ask for a commitment that he or she will come to the next session. We have found that stating that you are concerned the patient might not come to the next session can paradoxically be helpful.

Having your receptionist call and remind patients the day before their visits might not be a good idea in many cases. Patients might think these calls relieve them of the responsibility for remembering to keep appointments.

With patients you think might miss appointments—especially those on a medication that requires careful monitoring—consider writing prescriptions to last no longer than the next appointment.

Occasional missed appointments

Don’t just let it go when patients occasionally miss appointments without adequate reason. Ignoring the problem lets it progress.

Resist the temptation to be courteous and say, “That’s all right” when patients apologize or give a reason for missing the session. Doing so gives a subtle message that missing appointments is acceptable.

Discussing the patients’ reasons for missing appointments might solve the problem at times. For example, patients might not mention transportation or child care problems.

Note in the chart when a patient does not come to an appointment so you can calculate how many have been missed. This notation also will remind you to address these missed appointments during the next visit. Because discussing missed appointments at the start of the session might seem confrontational or punitive, inquire about the reasons for missing the previous appointment in a gentle manner and later in the session.

Remind patients that therapy is the tool to solve their emotional problems and thus has a special place in their lives. If patients want to solve other problems, they must start by regularly attending therapy.

Repeatedly missed appointments

When a patient misses appointments repeatedly, take 1 or more sessions to discuss it. This has to be done before therapy can proceed effectively (of course you might need to postpone this discussion if the patient has experienced major stressful events or has other pressing clinical issues).

When doing this, resist the temptation to become sidetracked by other issues the patient brings up. You can let the patient vent for a few minutes, but don’t let most of the session go by before addressing the missed appointments.

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

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

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

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

HISTORY: ‘Unusual behavior’

Ms. L, age 44, has severe cerebral palsy and has used a wheelchair since childhood. Her mother, who had been her primary caretaker, died 12 years ago, and her stepsister has been caring for her since.

Ms. L’s primary care physician reports that the patient has been “acting out” lately and asks us to evaluate her “unusual behavior.” Six months ago, the physician prescribed escitalopram, 30 mg/d, to treat depressive symptoms stemming from her chronic neurologic disorder.

We interview Ms. L and her stepsister together. The patient says she has been depressed, irritable, and moody, and her stepsister confirms this. The patient shows no signs of distress during the interview, and her answers appear short and guarded.

The stepsister says she typically spends her day turning Ms. L to prevent bedsores, feeding and bathing her, replacing her urinary catheter and emptying her urinary bag, and helping her to the bathroom. At day’s end, the stepsister has little time to spend with her husband or for other activities. She says at times she resents tending to Ms. L’s constant needs and feels “stressed out.”

We diagnose Ms. L with a mood disorder caused by a general medical condition. We continue escitalopram, 30 mg/d, and add oxcarbazepine, 150 mg bid, to treat her irritability and lability.

FOLLOW-UP: ‘She’s abusing me’

At Ms. L’s follow-up visit 2 weeks later, we ask her stepsister to leave the examination room and interview the patient alone to gauge her emotional condition and insight.

Seconds later, Ms. L starts crying hysterically, then reports that for 12 years her stepsister has been beating her, usually after she requests something. Yesterday, she says, her stepsister started punching her after she asked to be taken to the park.

Ms. L says the abuse is escalating and now occurs daily. She says she is covered with bruises from the last beating, although no bruises are visible at first glance. Afraid to go home with her stepsister, she pleads for help.

1. call the primary care physician for collateral information
   
2. examine Ms. L for bruises
   
3. get the stepsister’s side of the story
   
4. contact state protective services
   
5. all of the above
   

The authors’ observations

Is Ms. L being physically abused, or is a psychiatric condition driving her to fabricate these allegations?

We saw nothing suspicious during the first interview with the stepsister, although she acknowledged difficulty coping with Ms. L’s constant requests (Box 1).¹ Caring for a severely disabled person day in and day out can be trying for both the caregiver and her family, and the stepsister could be taking her frustrations out on Ms. L.

Until proven otherwise, we must assume Ms. L is being harmed and seek more information. We also must watch for signs of a delusional or factitious disorder or malingering—any of which would suggest the allegations are false.

Box 1

HISTORY: A second opinion

We ask Ms. L if we can discuss the allegations with her and her stepsister, but she fears retaliation and insists that we not speak to the caretaker.

We then call Ms. L’s primary care physician, who has been managing her care for several years. He says the patient has begged him numerous times for protection from her stepsister, but adds he has found no evidence of abuse. He notes that he has witnessed tension between the 2 women during office visits and cannot dismiss the possibility of abuse.

The attending psychiatrist performs a brief physical exam with the resident looking on but finds no bruises, excoriations, or unusual scarring on her arms and legs. Because our outpatient clinic lacks an examination room, we do not perform a whole-body exam.

We then notify state protective services. There, an agent tells us that in the past year, Ms. L has made 4 allegations of caretaker abuse, none of which were substantiated after extensive investigation. The agent says her office will assign a case worker but considers the case a low priority.

When we inform Ms. L of our findings, she frantically insists that her caretaker is beating her once a week and that the abuse has gone undetected. We become skeptical, recalling that Ms. L earlier said the beatings were daily.

Ms. L says she is afraid to go home and wonders where she can stay. Having no friends or other family members nearby, she requests hospitalization.

At this point, I would:

1. discharge Ms. L to a safe house with close follow-up
   
2. hospitalize her for safety and diagnostic clarification
   
3. discharge her to her stepsister with close follow-up
   

The authors’ observations

Ms. L’s allegations pose a medical, ethical, and legal challenge. Physical examination and input from a protective services officer suggest Ms. L is fabricating the allegations. On the other hand, if the accusations are true, sending Ms. L home with her stepsister would endanger her.

We could hospitalize the patient and substantiate the allegations later, but we cannot justify taxing limited hospital resources when the need is questionable. We cannot send her to a safe house because of her severe physical disability, nor can we discuss the allegations with her stepsister because Ms. L instructed us not to.

Box 2

DISPOSITION: Going home

After meeting with hospital officials and clinic staff, we decide that Ms. L does not meet admission criteria. We discharge her to her stepsister and see the patient again the next day.

The authors’ observations

Legal duty. Our legal duty to protect a suspected abuse victim depends on the jurisdiction in which treatment is delivered.

Many states do not require physicians to report suspected abuse, but this complicates the decision process. If the suspicion is correct, not reporting it might constitute malpractice or negligence and could provoke future lawsuits or complaints to the state medical board. Worse, the abuse may escalate and cause irreparable harm to the patient. Conversely, reporting unfounded suspicions of abuse can destroy the doctor-patient relationship, prompt the caregiver to retaliate against the patient, or inspire patients or caregivers to sue the physician.

If you suspect patient abuse and your state mandates reporting, contact the state protective services agency at once (seeRelated Resources,). Base your report on a thorough history and physical, psychiatric evaluation, and—when available—collateral information.

If your state does not mandate reporting, obtain the patient’s consent to file a complaint with state protective services. By providing informed consent, the patient gives permission to disclose protected health information, and confidentiality is not breached.

Be careful when obtaining informed consent, especially when the patient is ambivalent about reporting because of:

• fear of retaliation from the abuser
  
• fear of the social stigma associated with abuse
  
• or the patient’s false belief that she deserves the abuse.
  

Ethical responsibility. Even if our legal responsibility is minimal, we should go further to do what is best for the patient.

Texas, for example, does not require physicians to hospitalize or find a safe environment for a suspected abuse victim.² But if you see evidence of abuse, notify authorities and offer the patient information about local safe houses, support groups, and social services—even if not mandated by law. If resources are available, consider hospitalizing the patient and work with his or her social worker, therapist, or clergy to orchestrate outpatient services.

Whether or not abuse has occurred, empathizing with the caretaker about the difficulty of caring for the patient could diminish the caretaker’s stress and reduce the risk of abuse.

FOLLOW-UP: Truth or delusion?

At her appointment the next day, Ms. L says things are fine at home and does not bring up the abuse allegations. We then see her every 3 days for 2 weeks, weekly for 4 weeks, and every 3 weeks thereafter as the apparent risk of abuse diminishes. At each visit, she says her caretaker is not beating her but occasionally complains that she is verbally abusive.

Three weeks after her first follow-up, Ms. L enters the examination room agitated and frightened; she says another patient in the waiting room has just tried to strangle her for no apparent reason. Upon questioning, office staff say they saw no attack and note that the accused patient is a feeble woman with no history of violence; we doubt she assaulted Ms. L.

Ms. L suffers from:

1. repeated physical abuse
   
2. delusional disorder
   
3. factitious disorder
   
4. malingering
   

The authors’ observations

Although Ms. L clearly was not assaulted in the waiting room, this complaint is key to understanding her case. Although whether she is being abused at home remains unclear, evidence increasingly suggests that she suffers from delusions.

Delusions are beliefs that are fixed, false, and not ordinarily accepted by others in a patient’s culture or subculture.³ Delusional disorder is characterized by nonbizarre delusions lasting >1 month (>3 months according to ICD-10 criteria)⁴ with relatively preserved functioning and without prominent hallucinations. DSM-IV-TR defines bizarre delusions as “clearly implausible, not understandable, and not derived from ordinary life experience.”^4,5

Ms. L most likely has a paranoid or persecutory type delusional disorder in which she is convinced she is being harmed. Her delusional thoughts might yield mood symptoms such as anger and irritability, and she might become assaultive. Often, such patients are extraordinarily determined to succeed against “the conspirators” and frequently appeal to the legal system or law enforcement.³

Differentiating between a patient’s delusions and reality can be difficult, leading clinicians to seek collateral information from family, past medical records, or providers to establish a diagnosis. The delusions might become less circumscribed over time, or additional information might clear the clinical picture.

Ms. L’s psychological makeup might help us rule out other diagnoses. Her request for hospitalization, for example, could suggest factitious illness, but she is disabled enough to play the sick role without manufacturing symptoms. Also, she seeks hospitalization because she has no family or friends to turn to. We rule out malingering because Ms. L has nothing to gain by accusing a stranger of choking her in the waiting room.

Treating delusional disorder

Pharmacotherapy and psychotherapy typically are used together to treat delusional disorder.

Pharmacotherapy. Antipsychotics such as olanzapine, 5 to 10 mg nightly, or risperidone, 1 to 2 mg nightly, can decrease the delusional thoughts’ intensity and frequency, allowing patients to function more appropriately.³ If 2 or more antipsychotic trials do not control delusional thoughts, consider starting clozapine at 300 mg/d and titrating to 900 mg/d.

Add an antidepressant if delusional thinking causes depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, 10 to 20 mg/d, or fluoxetine, 20 to 40 mg/d, are a good starting point. Consider other antidepressant types if SSRIs do not work.

Adjunctive benzodiazepines such as clonazepam, 1 to 2 mg/d, or lorazepam, 1 to 2 mg bid as needed, can help manage acute anxiety or agitation stemming from delusions.

Once rapport is established, consider challenging delusional beliefs by having the patient list evidence supporting or refuting the delusions. Be careful not to confront delusional thinking too quickly or aggressively, as this approach often does not change the patient’s beliefs and weakens the therapeutic alliance.³

TREATMENT: Fewer complaints

We still see Ms. L every 3 weeks for supportive psychotherapy and medication management. We continue oxcarbazepine, 150 mg bid, and escitalopram, 30 mg/d, and add risperidone, 1 mg at bedtime, to target her delusional thinking, lability, and irritability.

Over 6 months, Ms. L’s complaints of abuse become less emphatic. She endorses the abuse less frequently—every 3 to 4 visits—and only if the clinician specifically asks about it. Most often, she denies abuse is occurring but says it happened previously. At each visit, we document her statements and explain in her chart why we have not notified adult protective services or police.

Related resources

• National Adult Protective Services Association. Links to adult protection agencies nationwide. www.apsnetwork.org.
  
• National Center on Elder Abuse. www.elderabusecenter.org.
  

• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Oxcarbazepine • Trileptal
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  

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

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

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

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

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

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

A wide differential diagnosis

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

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

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

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

Table 1

HIV-associated CNS infections

Neuropsychiatric side effects of antiretroviral medications

STEP 1 Perform initial exams

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

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

CASE CONTINUED

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

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

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

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

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

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

CASE CONTINUED

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

STEP 2 Evaluate lab results

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

CASE CONTINUED

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

Box

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

STEP 3 Order neuroimaging

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

CASE CONTINUED

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

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

STEP 4 Perform neuropsychological testing

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

CASE CONTINUED

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

STEP 5 Synthesize all data to make a diagnosis

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

CASE CONTINUED

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

Table 3

Staging system for HIV-associated dementia

CASE CONTINUED

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

Related Resources

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

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

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

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

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

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

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

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

A wide differential diagnosis

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

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

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

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

Table 1

HIV-associated CNS infections

Neuropsychiatric side effects of antiretroviral medications

STEP 1 Perform initial exams

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

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

CASE CONTINUED

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

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

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

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

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

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

CASE CONTINUED

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

STEP 2 Evaluate lab results

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

CASE CONTINUED

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

Box

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

STEP 3 Order neuroimaging

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

CASE CONTINUED

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

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

STEP 4 Perform neuropsychological testing

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

CASE CONTINUED

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

STEP 5 Synthesize all data to make a diagnosis

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

CASE CONTINUED

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

Table 3

Staging system for HIV-associated dementia

CASE CONTINUED

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

Related Resources

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

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

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

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

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

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

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

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

A wide differential diagnosis

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

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

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

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

Table 1

HIV-associated CNS infections

Neuropsychiatric side effects of antiretroviral medications

STEP 1 Perform initial exams

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

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

CASE CONTINUED

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

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

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

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

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

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

CASE CONTINUED

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

STEP 2 Evaluate lab results

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

CASE CONTINUED

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

Box

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

STEP 3 Order neuroimaging

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

CASE CONTINUED

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

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

STEP 4 Perform neuropsychological testing

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

CASE CONTINUED

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

STEP 5 Synthesize all data to make a diagnosis

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

CASE CONTINUED

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

Table 3

Staging system for HIV-associated dementia

CASE CONTINUED

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

Related Resources

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

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

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

Although many patients with insomnia respond to standard treatments, some continue to experience insufficient sleep. When your patient appears “treatment-resistant,” you may be tempted to add another therapy or try an unorthodox medication. But choosing an appropriate next treatment is impossible without first looking back for a rationale:

• Have you overlooked one of insomnia’s many causes?
  
• Have you customized treatment for this patient?
  
• Is he or she unaware of behaviors that may be undermining attempts to sleep?
  

Refreshing sleep may elude some thoroughly evaluated and optimally treated patients, but they comprise a small minority. You can help most chronic insomnia sufferers by re-evaluating their behaviors, comorbidities, sleep-wake cycles, and medications (Table 1).

Table 1

Recommended approach to treatment-resistant insomnia

‘3 Ps’ and 8 questions

Thirty percent of adults experience insomnia at least occasionally, and 10% have persistent insomnia. Women, older persons, and patients with chronic medical conditions such as diabetes mellitus and lung disease have higher insomnia rates than the general population.¹

An enormous variety of psychological and physiologic processes may influence sleep (Box 1). Multiple factors may contribute to an individual’s inability to achieve sufficient sleep, and the relative significance of these influences can shift over time. Factors that might trigger an insomnia episode are not necessarily those that maintain sleeplessness.

1 Does the patient have realistic goals for falling asleep and remaining asleep?

Patients view insomnia as being unable to sleep when they believe they should be sleeping. To be diagnosed as a disorder, insomnia must have daytime consequences associated with:

• difficulty falling asleep
  
• difficulty maintaining sleep
  
• awakening excessively early
  
• or experiencing nonrestorative sleep.
  

Recommendation. Determine how the patient defines “having insomnia” (there are no absolute thresholds). Ask how he or she is functioning during the day. Those who complain of imperfect nighttime sleep may admit that treatment has helped with the daytime symptoms that prompted them to seek treatment.

If daytime symptoms have diminished, reassure the patient that treatment apparently is helping. Patients are less likely to focus on perceived nighttime impairment when their distress about daytime functioning has eased.

Also determine if the patient has followed recommended treatment. Cognitive-behavioral therapy (CBT) may increase adherence to behavioral changes, sleep hygiene, and medication schedules.

2 Have I identified and optimally managed comorbidities?

Identifying comorbidities that may contribute to chronic insomnia is particularly important because managing these conditions may alleviate the sleep disturbance. Pain or discomfort caused by a medical condition may undermine sleep quality. Certain cardiovascular, pulmonary, endocrine, neurologic, rheumatologic, and orthopedic disorders are associated with insomnia.

Most patients experiencing exacerbations of mood and anxiety disorders suffer insomnia, and many other psychiatric disorders are associated with sleep disruption.

Box 1

Insomnia often accompanies substance abuse and may continue after the patient stops abusing drugs or alcohol. Abused stimulants and sedatives can worsen sleep quality, and discontinuation can cause acute and chronic sleep disruption.

Recommendation. Treat mood and anxiety disorders independently of insomnia. Minimize pain and discomfort from medical conditions. Address substance abuse, and dispel patients’ notion that alcohol is a sleep aid.

Order sleep laboratory testing for patients at risk for sleep apnea, based on their history, physical exam—including obesity, upper airway anatomy, and neck circumference (collar size ≥17 inches)—and informant reports of snoring and breathing patterns.

3 Is the patient taking medications with stimulating effects?

Because insomnia is highly comorbid with mood and anxiety disorders, patients with insomnia often are prescribed antidepressants. Although some are sedating, antidepressants such as selective serotonin reuptake inhibitors are likely to be stimulating.

Recommendation. When insomnia persists, assess the potential effects of prescribed and over-the-counter (OTC) medications. Consider possible pharmacologic effects of aging that can make patients more sensitive to medications.

Also educate patients about the long-acting effects of caffeine and its varied sources, such as energy drinks and OTC products. Some patients will benefit from completely avoiding caffeine, whereas others may do fine restricting coffee to 1 or 2 cups in the morning. A good general practice is to avoid all caffeine after lunchtime.

Box 2

4 Does the patient’s insomnia have a homeostatic component?

Circadian rhythms and a homeostatic sleep drive are temporally linked in regulating the normal routine of nighttime sleep alternating with day and evening wakefulness.^5,6 The sleep drive promotes a sleep-to-waking ratio of approximately 1:2 (an average of 8 hours sleep per 24 hours). Adequate sleep, from the homeostatic perspective, could be achieved during any hours of the day or night.

Acute sleep deprivation may result from extended wakefulness—such as staying up all night to study for an exam. Chronic sleep deprivation may occur during successive 24-hour periods with insufficient sleep. Both patterns are associated with increasing subjective sleepiness and ultimately with cognitive impairment.

• is low throughout the daytime
  
• rises during the evening as bedtime approaches
  
• plateaus during nighttime sleep hours
  
• decreases as the normal morning wake time approaches.
  

Typically, people are more alert in the evening than at any other time in the 24-hour cycle. As bedtime approaches, rising melatonin interacts with SCN melatonin receptors and decreases circadian arousal. Normal sleep onset then can occur rapidly at bedtime, when the homeostatic sleep drive is unopposed.

Nighttime sleep initially is promoted by the homeostatic sleep drive. However, the homeostatic sleep pressure is reversed by sleep and thus decreases as sleep continues during the night. The circadian system promotes minimum stimulation during the latter sleep hours, sustaining total sleep for approximately 8 hours.

Consequences. Individual circadian timing tendencies may affect when people experience alertness and sleepiness and may be associated with persistent complaints of sleep onset difficulty or early morning awakening.⁷ Napping may reduce the homeostatic sleepiness available to aid bedtime sleep onset. Mismatched homeostatic and circadian processes often prevent shift workers from achieving satisfactory sleep.

Recommendation. Have the patient keep a sleep log to identify the time and duration of sleep episodes throughout the 24-hour cycle. Actigraphy may provide useful information about sleep-wake patterns.

5 Are circadian rhythm patterns contributing to insomnia?

Overlooking circadian rhythms’ effects on insomnia can lead to apparent treatment failure.⁸ Although the circadian system typically promotes sleep from about 10 pm to midnight until about 6 to 8 am, some individuals have long-standing predispositions for earlier or later sleep episodes.

An advanced circadian phase leads to sleepiness and the ability to fall asleep early in the evening, followed by a tendency to awaken spontaneously relatively early in the morning. In extreme cases, patients with these “lark” tendencies may be diagnosed with advanced sleep phase disorder. Persistent early morning awakening insomnia and sleep maintenance complaints are common.

A delayed circadian phase is associated with inability to fall asleep at a typical late evening bedtime and difficulty awakening at a desired time the following morning. In extreme cases, individuals may sleep from very late at night until the following afternoon. These markedly delayed schedules may be obvious, but the circadian contribution may not be recognized in less severe cases.

People with this predisposition may achieve optimum sleep by following their delayed circadian tendency, but school and work demands often conflict with this approach. They may develop chronic sleep deprivation from late sleep onset coupled with forced morning awakenings. Complaints of chronic difficulty with sleep onset are common.

Recommendation. Have the patient keep a sleep log to demonstrate advanced or delayed circadian phase tendencies. Determine if the patient is a shift worker who is attempting to sleep in the daytime. Consider prescribing ramelteon—a melatonin agonist—and providing strategic bright light exposure:

• in the evening for advanced circadian phase patients
  
• in the morning for delayed circadian phase patients.⁸
  

6 Is the patient following appropriate sleep hygiene?

Sleep hygiene will not necessarily cure chronic insomnia, but inattention to basic guidelines (Table 2) can undermine other treatments. When re-evaluating patients with chronic insomnia, give special attention to their alcohol and caffeine intake, regularity of bedtime and wake-up times, meal times, and the bedroom environment. Advise patients to remove televisions from the bedroom, for example.

CBT that is effective for chronic insomnia typically blends sleep hygiene with education, cognitive psychotherapy, and specific instructions regarding bedtime schedules.^9,10 Relaxation techniques also may be beneficial.

Consider consulting with a sleep specialist if the patient has not been evaluated at a sleep center. Some sleep centers offer CBT.

Table 2

Patient education: Sleep hygiene guidelines

7 Does the patient regularly experience anxiety and tension as bedtime approaches or spend excessive wakeful time in bed?

Patients who tend to be anxious, depressive, or emotionally reactive are at increased risk for developing an insomnia episode. They then may develop conditioned hyperarousal associated with preparing for and getting into bed, which perpetuates insomnia.

Some patients spend long periods in bed, hoping to achieve any possible sleep that night. Extended time in bed can perpetuate insomnia by increasing frustrating time awake, thereby reinforcing the association between the bed and wakefulness.

Recommendation. CBT often helps ease these conditioned responses.

Stimulus control can help anxious individuals reassociate the bed, bedroom, and bedtime routines with sleep onset, rather than sleep-destructive tension. Advise patients to go to bed in the evening when they feel they can fall asleep. If they do not fall asleep within 10 to 15 minutes or experience their usual worry and frustration about not sleeping, instruct them to leave the bed and try again later. Also tell them to avoid daytime napping.

Sleep restriction therapy may help patients with excessive wakefulness in bed by limiting sleep opportunity to defined hours of the night. For example, a patient who reports getting 5 hours of sleep would be scheduled for 5 hours in bed. If his typical arising time is 7 am, he would not go to bed until 2 am. When his sleep log shows he has slept 90% of the time in bed for 5 consecutive nights, he can go to bed 15 to 30 minutes earlier. Over time, as this process is repeated, patients spend greater amounts of time sleeping while in bed.

Sleep restriction creates a degree of sleep deprivation that may enhance sleep onset and maintenance. Caution patients not to drive or perform hazardous activities while sleep-deprived.

8 Has the patient been prescribed appropriate doses of medications with appropriate indications?

Chronic insomnia sufferers often try to get more sleep by using alcohol, food supplement remedies, and OTC antihistamine sleep aids—none of which has demonstrated efficacy for treating insomnia. Although sedating prescription medications may be recommended for comorbid conditions, many also are prescribed off-label to promote sleep.

Examples include sedating antidepressants, antipsychotics, antihistamines, anticonvulsants, and benzodiazepines that are not indicated for insomnia. Little or no evidence supports these medications as safe and efficacious for treating insomnia, and important safety concerns are associated with their use.

The BZRA category includes 5 benzodiazepines and 4 nonbenzodiazepine formulations. Half-lives vary from approximately 1 hour to several days. Compared with benzodiazepines, nonbenzodiazepines have greater selectivity for GABAA receptor complexes incorporating the alpha-1 sub-unit subtype, which may confer some safety and tolerability advantages. One extended-release formulation is available. All may be beneficial for sleep onset, and some have indications for sleep maintenance difficulty.

Ramelteon is a nonsedating selective melatonin receptor agonist approved for treating insomnia characterized by sleep onset difficulty. This agent—which attenuates evening circadian arousal—may help promote sleep onset and enhance sleep during the early part of the night.

Administration. Inadequate dosing of insomnia medications may cause treatment to fail, but prescribing beyond approved ranges is rarely necessary. High sedative doses increase the risk of adverse effects, and patients may sleep no better. Adverse effects may include somnolence, headache, dizziness, nausea, diarrhea, and anterograde amnesia. Rarely patients may exhibit sleep walking or confused behaviors within a few hours after taking a hypnotic dose.

Recommendation. Customize your selection of FDA-approved insomnia medications. Consider whether your patient needs medication for sleep onset or sleep maintenance. In most cases, prescribe within dosing ranges listed in Table 3

Table 3

Insomnia treatment: FDA-approved medications

Related Resources

• American Academy of Sleep Medicine. www.aasmnet.org.
  
• National Sleep Foundation. www.sleepfoundation.org.
  
• NIH National Center for Sleep Disorders Research. www.nhlbi.nih.gov/about/ncsdr.
  

Drug brand names

• Estazolam • ProSom
  
• Eszopiclone • Lunesta
  
• Flurazepam • Dalmane
  
• Quazepam • Doral
  
• Ramelteon • Rozerem
  
• Temazepam • Restoril
  
• Triazolam • Halcion
  
• Zaleplon • Sonata
  
• Zolpidem • Ambien
  
• Zolpidem ER • Ambien CR
  

Disclosure

Dr. Neubauer is a consultant to Neurocrine Biosciences, sanofi-aventis, and Takeda Pharmaceuticals North America and a speaker for sanofi-aventis and Takeda Pharmaceuticals North America.

Although many patients with insomnia respond to standard treatments, some continue to experience insufficient sleep. When your patient appears “treatment-resistant,” you may be tempted to add another therapy or try an unorthodox medication. But choosing an appropriate next treatment is impossible without first looking back for a rationale:

• Have you overlooked one of insomnia’s many causes?
  
• Have you customized treatment for this patient?
  
• Is he or she unaware of behaviors that may be undermining attempts to sleep?
  

Refreshing sleep may elude some thoroughly evaluated and optimally treated patients, but they comprise a small minority. You can help most chronic insomnia sufferers by re-evaluating their behaviors, comorbidities, sleep-wake cycles, and medications (Table 1).

Table 1

Recommended approach to treatment-resistant insomnia

‘3 Ps’ and 8 questions

Thirty percent of adults experience insomnia at least occasionally, and 10% have persistent insomnia. Women, older persons, and patients with chronic medical conditions such as diabetes mellitus and lung disease have higher insomnia rates than the general population.¹

An enormous variety of psychological and physiologic processes may influence sleep (Box 1). Multiple factors may contribute to an individual’s inability to achieve sufficient sleep, and the relative significance of these influences can shift over time. Factors that might trigger an insomnia episode are not necessarily those that maintain sleeplessness.

1 Does the patient have realistic goals for falling asleep and remaining asleep?

Patients view insomnia as being unable to sleep when they believe they should be sleeping. To be diagnosed as a disorder, insomnia must have daytime consequences associated with:

• difficulty falling asleep
  
• difficulty maintaining sleep
  
• awakening excessively early
  
• or experiencing nonrestorative sleep.
  

Recommendation. Determine how the patient defines “having insomnia” (there are no absolute thresholds). Ask how he or she is functioning during the day. Those who complain of imperfect nighttime sleep may admit that treatment has helped with the daytime symptoms that prompted them to seek treatment.

If daytime symptoms have diminished, reassure the patient that treatment apparently is helping. Patients are less likely to focus on perceived nighttime impairment when their distress about daytime functioning has eased.

Also determine if the patient has followed recommended treatment. Cognitive-behavioral therapy (CBT) may increase adherence to behavioral changes, sleep hygiene, and medication schedules.

2 Have I identified and optimally managed comorbidities?

Identifying comorbidities that may contribute to chronic insomnia is particularly important because managing these conditions may alleviate the sleep disturbance. Pain or discomfort caused by a medical condition may undermine sleep quality. Certain cardiovascular, pulmonary, endocrine, neurologic, rheumatologic, and orthopedic disorders are associated with insomnia.

Most patients experiencing exacerbations of mood and anxiety disorders suffer insomnia, and many other psychiatric disorders are associated with sleep disruption.

Box 1

Insomnia often accompanies substance abuse and may continue after the patient stops abusing drugs or alcohol. Abused stimulants and sedatives can worsen sleep quality, and discontinuation can cause acute and chronic sleep disruption.

Recommendation. Treat mood and anxiety disorders independently of insomnia. Minimize pain and discomfort from medical conditions. Address substance abuse, and dispel patients’ notion that alcohol is a sleep aid.

Order sleep laboratory testing for patients at risk for sleep apnea, based on their history, physical exam—including obesity, upper airway anatomy, and neck circumference (collar size ≥17 inches)—and informant reports of snoring and breathing patterns.

3 Is the patient taking medications with stimulating effects?

Because insomnia is highly comorbid with mood and anxiety disorders, patients with insomnia often are prescribed antidepressants. Although some are sedating, antidepressants such as selective serotonin reuptake inhibitors are likely to be stimulating.

Recommendation. When insomnia persists, assess the potential effects of prescribed and over-the-counter (OTC) medications. Consider possible pharmacologic effects of aging that can make patients more sensitive to medications.

Also educate patients about the long-acting effects of caffeine and its varied sources, such as energy drinks and OTC products. Some patients will benefit from completely avoiding caffeine, whereas others may do fine restricting coffee to 1 or 2 cups in the morning. A good general practice is to avoid all caffeine after lunchtime.

Box 2

4 Does the patient’s insomnia have a homeostatic component?

Circadian rhythms and a homeostatic sleep drive are temporally linked in regulating the normal routine of nighttime sleep alternating with day and evening wakefulness.^5,6 The sleep drive promotes a sleep-to-waking ratio of approximately 1:2 (an average of 8 hours sleep per 24 hours). Adequate sleep, from the homeostatic perspective, could be achieved during any hours of the day or night.

Acute sleep deprivation may result from extended wakefulness—such as staying up all night to study for an exam. Chronic sleep deprivation may occur during successive 24-hour periods with insufficient sleep. Both patterns are associated with increasing subjective sleepiness and ultimately with cognitive impairment.

• is low throughout the daytime
  
• rises during the evening as bedtime approaches
  
• plateaus during nighttime sleep hours
  
• decreases as the normal morning wake time approaches.
  

Typically, people are more alert in the evening than at any other time in the 24-hour cycle. As bedtime approaches, rising melatonin interacts with SCN melatonin receptors and decreases circadian arousal. Normal sleep onset then can occur rapidly at bedtime, when the homeostatic sleep drive is unopposed.

Nighttime sleep initially is promoted by the homeostatic sleep drive. However, the homeostatic sleep pressure is reversed by sleep and thus decreases as sleep continues during the night. The circadian system promotes minimum stimulation during the latter sleep hours, sustaining total sleep for approximately 8 hours.

Consequences. Individual circadian timing tendencies may affect when people experience alertness and sleepiness and may be associated with persistent complaints of sleep onset difficulty or early morning awakening.⁷ Napping may reduce the homeostatic sleepiness available to aid bedtime sleep onset. Mismatched homeostatic and circadian processes often prevent shift workers from achieving satisfactory sleep.

Recommendation. Have the patient keep a sleep log to identify the time and duration of sleep episodes throughout the 24-hour cycle. Actigraphy may provide useful information about sleep-wake patterns.

5 Are circadian rhythm patterns contributing to insomnia?

Overlooking circadian rhythms’ effects on insomnia can lead to apparent treatment failure.⁸ Although the circadian system typically promotes sleep from about 10 pm to midnight until about 6 to 8 am, some individuals have long-standing predispositions for earlier or later sleep episodes.

An advanced circadian phase leads to sleepiness and the ability to fall asleep early in the evening, followed by a tendency to awaken spontaneously relatively early in the morning. In extreme cases, patients with these “lark” tendencies may be diagnosed with advanced sleep phase disorder. Persistent early morning awakening insomnia and sleep maintenance complaints are common.

A delayed circadian phase is associated with inability to fall asleep at a typical late evening bedtime and difficulty awakening at a desired time the following morning. In extreme cases, individuals may sleep from very late at night until the following afternoon. These markedly delayed schedules may be obvious, but the circadian contribution may not be recognized in less severe cases.

People with this predisposition may achieve optimum sleep by following their delayed circadian tendency, but school and work demands often conflict with this approach. They may develop chronic sleep deprivation from late sleep onset coupled with forced morning awakenings. Complaints of chronic difficulty with sleep onset are common.

Recommendation. Have the patient keep a sleep log to demonstrate advanced or delayed circadian phase tendencies. Determine if the patient is a shift worker who is attempting to sleep in the daytime. Consider prescribing ramelteon—a melatonin agonist—and providing strategic bright light exposure:

• in the evening for advanced circadian phase patients
  
• in the morning for delayed circadian phase patients.⁸
  

6 Is the patient following appropriate sleep hygiene?

Sleep hygiene will not necessarily cure chronic insomnia, but inattention to basic guidelines (Table 2) can undermine other treatments. When re-evaluating patients with chronic insomnia, give special attention to their alcohol and caffeine intake, regularity of bedtime and wake-up times, meal times, and the bedroom environment. Advise patients to remove televisions from the bedroom, for example.

CBT that is effective for chronic insomnia typically blends sleep hygiene with education, cognitive psychotherapy, and specific instructions regarding bedtime schedules.^9,10 Relaxation techniques also may be beneficial.

Consider consulting with a sleep specialist if the patient has not been evaluated at a sleep center. Some sleep centers offer CBT.

Table 2

Patient education: Sleep hygiene guidelines

7 Does the patient regularly experience anxiety and tension as bedtime approaches or spend excessive wakeful time in bed?

Patients who tend to be anxious, depressive, or emotionally reactive are at increased risk for developing an insomnia episode. They then may develop conditioned hyperarousal associated with preparing for and getting into bed, which perpetuates insomnia.

Some patients spend long periods in bed, hoping to achieve any possible sleep that night. Extended time in bed can perpetuate insomnia by increasing frustrating time awake, thereby reinforcing the association between the bed and wakefulness.

Recommendation. CBT often helps ease these conditioned responses.

Stimulus control can help anxious individuals reassociate the bed, bedroom, and bedtime routines with sleep onset, rather than sleep-destructive tension. Advise patients to go to bed in the evening when they feel they can fall asleep. If they do not fall asleep within 10 to 15 minutes or experience their usual worry and frustration about not sleeping, instruct them to leave the bed and try again later. Also tell them to avoid daytime napping.

Sleep restriction therapy may help patients with excessive wakefulness in bed by limiting sleep opportunity to defined hours of the night. For example, a patient who reports getting 5 hours of sleep would be scheduled for 5 hours in bed. If his typical arising time is 7 am, he would not go to bed until 2 am. When his sleep log shows he has slept 90% of the time in bed for 5 consecutive nights, he can go to bed 15 to 30 minutes earlier. Over time, as this process is repeated, patients spend greater amounts of time sleeping while in bed.

Sleep restriction creates a degree of sleep deprivation that may enhance sleep onset and maintenance. Caution patients not to drive or perform hazardous activities while sleep-deprived.

8 Has the patient been prescribed appropriate doses of medications with appropriate indications?

Chronic insomnia sufferers often try to get more sleep by using alcohol, food supplement remedies, and OTC antihistamine sleep aids—none of which has demonstrated efficacy for treating insomnia. Although sedating prescription medications may be recommended for comorbid conditions, many also are prescribed off-label to promote sleep.

Examples include sedating antidepressants, antipsychotics, antihistamines, anticonvulsants, and benzodiazepines that are not indicated for insomnia. Little or no evidence supports these medications as safe and efficacious for treating insomnia, and important safety concerns are associated with their use.

The BZRA category includes 5 benzodiazepines and 4 nonbenzodiazepine formulations. Half-lives vary from approximately 1 hour to several days. Compared with benzodiazepines, nonbenzodiazepines have greater selectivity for GABAA receptor complexes incorporating the alpha-1 sub-unit subtype, which may confer some safety and tolerability advantages. One extended-release formulation is available. All may be beneficial for sleep onset, and some have indications for sleep maintenance difficulty.

Ramelteon is a nonsedating selective melatonin receptor agonist approved for treating insomnia characterized by sleep onset difficulty. This agent—which attenuates evening circadian arousal—may help promote sleep onset and enhance sleep during the early part of the night.

Administration. Inadequate dosing of insomnia medications may cause treatment to fail, but prescribing beyond approved ranges is rarely necessary. High sedative doses increase the risk of adverse effects, and patients may sleep no better. Adverse effects may include somnolence, headache, dizziness, nausea, diarrhea, and anterograde amnesia. Rarely patients may exhibit sleep walking or confused behaviors within a few hours after taking a hypnotic dose.

Recommendation. Customize your selection of FDA-approved insomnia medications. Consider whether your patient needs medication for sleep onset or sleep maintenance. In most cases, prescribe within dosing ranges listed in Table 3

Table 3

Insomnia treatment: FDA-approved medications

Related Resources

• American Academy of Sleep Medicine. www.aasmnet.org.
  
• National Sleep Foundation. www.sleepfoundation.org.
  
• NIH National Center for Sleep Disorders Research. www.nhlbi.nih.gov/about/ncsdr.
  

Drug brand names

• Estazolam • ProSom
  
• Eszopiclone • Lunesta
  
• Flurazepam • Dalmane
  
• Quazepam • Doral
  
• Ramelteon • Rozerem
  
• Temazepam • Restoril
  
• Triazolam • Halcion
  
• Zaleplon • Sonata
  
• Zolpidem • Ambien
  
• Zolpidem ER • Ambien CR
  

Disclosure

Dr. Neubauer is a consultant to Neurocrine Biosciences, sanofi-aventis, and Takeda Pharmaceuticals North America and a speaker for sanofi-aventis and Takeda Pharmaceuticals North America.

Although many patients with insomnia respond to standard treatments, some continue to experience insufficient sleep. When your patient appears “treatment-resistant,” you may be tempted to add another therapy or try an unorthodox medication. But choosing an appropriate next treatment is impossible without first looking back for a rationale:

• Have you overlooked one of insomnia’s many causes?
  
• Have you customized treatment for this patient?
  
• Is he or she unaware of behaviors that may be undermining attempts to sleep?
  

Refreshing sleep may elude some thoroughly evaluated and optimally treated patients, but they comprise a small minority. You can help most chronic insomnia sufferers by re-evaluating their behaviors, comorbidities, sleep-wake cycles, and medications (Table 1).

Table 1

Recommended approach to treatment-resistant insomnia

‘3 Ps’ and 8 questions

Thirty percent of adults experience insomnia at least occasionally, and 10% have persistent insomnia. Women, older persons, and patients with chronic medical conditions such as diabetes mellitus and lung disease have higher insomnia rates than the general population.¹

An enormous variety of psychological and physiologic processes may influence sleep (Box 1). Multiple factors may contribute to an individual’s inability to achieve sufficient sleep, and the relative significance of these influences can shift over time. Factors that might trigger an insomnia episode are not necessarily those that maintain sleeplessness.

1 Does the patient have realistic goals for falling asleep and remaining asleep?

Patients view insomnia as being unable to sleep when they believe they should be sleeping. To be diagnosed as a disorder, insomnia must have daytime consequences associated with:

• difficulty falling asleep
  
• difficulty maintaining sleep
  
• awakening excessively early
  
• or experiencing nonrestorative sleep.
  

Recommendation. Determine how the patient defines “having insomnia” (there are no absolute thresholds). Ask how he or she is functioning during the day. Those who complain of imperfect nighttime sleep may admit that treatment has helped with the daytime symptoms that prompted them to seek treatment.

If daytime symptoms have diminished, reassure the patient that treatment apparently is helping. Patients are less likely to focus on perceived nighttime impairment when their distress about daytime functioning has eased.

Also determine if the patient has followed recommended treatment. Cognitive-behavioral therapy (CBT) may increase adherence to behavioral changes, sleep hygiene, and medication schedules.

2 Have I identified and optimally managed comorbidities?

Identifying comorbidities that may contribute to chronic insomnia is particularly important because managing these conditions may alleviate the sleep disturbance. Pain or discomfort caused by a medical condition may undermine sleep quality. Certain cardiovascular, pulmonary, endocrine, neurologic, rheumatologic, and orthopedic disorders are associated with insomnia.

Most patients experiencing exacerbations of mood and anxiety disorders suffer insomnia, and many other psychiatric disorders are associated with sleep disruption.

Box 1

Insomnia often accompanies substance abuse and may continue after the patient stops abusing drugs or alcohol. Abused stimulants and sedatives can worsen sleep quality, and discontinuation can cause acute and chronic sleep disruption.

Recommendation. Treat mood and anxiety disorders independently of insomnia. Minimize pain and discomfort from medical conditions. Address substance abuse, and dispel patients’ notion that alcohol is a sleep aid.

Order sleep laboratory testing for patients at risk for sleep apnea, based on their history, physical exam—including obesity, upper airway anatomy, and neck circumference (collar size ≥17 inches)—and informant reports of snoring and breathing patterns.

3 Is the patient taking medications with stimulating effects?

Because insomnia is highly comorbid with mood and anxiety disorders, patients with insomnia often are prescribed antidepressants. Although some are sedating, antidepressants such as selective serotonin reuptake inhibitors are likely to be stimulating.

Recommendation. When insomnia persists, assess the potential effects of prescribed and over-the-counter (OTC) medications. Consider possible pharmacologic effects of aging that can make patients more sensitive to medications.

Also educate patients about the long-acting effects of caffeine and its varied sources, such as energy drinks and OTC products. Some patients will benefit from completely avoiding caffeine, whereas others may do fine restricting coffee to 1 or 2 cups in the morning. A good general practice is to avoid all caffeine after lunchtime.

Box 2

4 Does the patient’s insomnia have a homeostatic component?

Circadian rhythms and a homeostatic sleep drive are temporally linked in regulating the normal routine of nighttime sleep alternating with day and evening wakefulness.^5,6 The sleep drive promotes a sleep-to-waking ratio of approximately 1:2 (an average of 8 hours sleep per 24 hours). Adequate sleep, from the homeostatic perspective, could be achieved during any hours of the day or night.

Acute sleep deprivation may result from extended wakefulness—such as staying up all night to study for an exam. Chronic sleep deprivation may occur during successive 24-hour periods with insufficient sleep. Both patterns are associated with increasing subjective sleepiness and ultimately with cognitive impairment.

• is low throughout the daytime
  
• rises during the evening as bedtime approaches
  
• plateaus during nighttime sleep hours
  
• decreases as the normal morning wake time approaches.
  

Typically, people are more alert in the evening than at any other time in the 24-hour cycle. As bedtime approaches, rising melatonin interacts with SCN melatonin receptors and decreases circadian arousal. Normal sleep onset then can occur rapidly at bedtime, when the homeostatic sleep drive is unopposed.

Nighttime sleep initially is promoted by the homeostatic sleep drive. However, the homeostatic sleep pressure is reversed by sleep and thus decreases as sleep continues during the night. The circadian system promotes minimum stimulation during the latter sleep hours, sustaining total sleep for approximately 8 hours.

Consequences. Individual circadian timing tendencies may affect when people experience alertness and sleepiness and may be associated with persistent complaints of sleep onset difficulty or early morning awakening.⁷ Napping may reduce the homeostatic sleepiness available to aid bedtime sleep onset. Mismatched homeostatic and circadian processes often prevent shift workers from achieving satisfactory sleep.

Recommendation. Have the patient keep a sleep log to identify the time and duration of sleep episodes throughout the 24-hour cycle. Actigraphy may provide useful information about sleep-wake patterns.

5 Are circadian rhythm patterns contributing to insomnia?

Overlooking circadian rhythms’ effects on insomnia can lead to apparent treatment failure.⁸ Although the circadian system typically promotes sleep from about 10 pm to midnight until about 6 to 8 am, some individuals have long-standing predispositions for earlier or later sleep episodes.

An advanced circadian phase leads to sleepiness and the ability to fall asleep early in the evening, followed by a tendency to awaken spontaneously relatively early in the morning. In extreme cases, patients with these “lark” tendencies may be diagnosed with advanced sleep phase disorder. Persistent early morning awakening insomnia and sleep maintenance complaints are common.

A delayed circadian phase is associated with inability to fall asleep at a typical late evening bedtime and difficulty awakening at a desired time the following morning. In extreme cases, individuals may sleep from very late at night until the following afternoon. These markedly delayed schedules may be obvious, but the circadian contribution may not be recognized in less severe cases.

People with this predisposition may achieve optimum sleep by following their delayed circadian tendency, but school and work demands often conflict with this approach. They may develop chronic sleep deprivation from late sleep onset coupled with forced morning awakenings. Complaints of chronic difficulty with sleep onset are common.

Recommendation. Have the patient keep a sleep log to demonstrate advanced or delayed circadian phase tendencies. Determine if the patient is a shift worker who is attempting to sleep in the daytime. Consider prescribing ramelteon—a melatonin agonist—and providing strategic bright light exposure:

• in the evening for advanced circadian phase patients
  
• in the morning for delayed circadian phase patients.⁸
  

6 Is the patient following appropriate sleep hygiene?

Sleep hygiene will not necessarily cure chronic insomnia, but inattention to basic guidelines (Table 2) can undermine other treatments. When re-evaluating patients with chronic insomnia, give special attention to their alcohol and caffeine intake, regularity of bedtime and wake-up times, meal times, and the bedroom environment. Advise patients to remove televisions from the bedroom, for example.

CBT that is effective for chronic insomnia typically blends sleep hygiene with education, cognitive psychotherapy, and specific instructions regarding bedtime schedules.^9,10 Relaxation techniques also may be beneficial.

Consider consulting with a sleep specialist if the patient has not been evaluated at a sleep center. Some sleep centers offer CBT.

Table 2

Patient education: Sleep hygiene guidelines

7 Does the patient regularly experience anxiety and tension as bedtime approaches or spend excessive wakeful time in bed?

Patients who tend to be anxious, depressive, or emotionally reactive are at increased risk for developing an insomnia episode. They then may develop conditioned hyperarousal associated with preparing for and getting into bed, which perpetuates insomnia.

Some patients spend long periods in bed, hoping to achieve any possible sleep that night. Extended time in bed can perpetuate insomnia by increasing frustrating time awake, thereby reinforcing the association between the bed and wakefulness.

Recommendation. CBT often helps ease these conditioned responses.

Stimulus control can help anxious individuals reassociate the bed, bedroom, and bedtime routines with sleep onset, rather than sleep-destructive tension. Advise patients to go to bed in the evening when they feel they can fall asleep. If they do not fall asleep within 10 to 15 minutes or experience their usual worry and frustration about not sleeping, instruct them to leave the bed and try again later. Also tell them to avoid daytime napping.

Sleep restriction therapy may help patients with excessive wakefulness in bed by limiting sleep opportunity to defined hours of the night. For example, a patient who reports getting 5 hours of sleep would be scheduled for 5 hours in bed. If his typical arising time is 7 am, he would not go to bed until 2 am. When his sleep log shows he has slept 90% of the time in bed for 5 consecutive nights, he can go to bed 15 to 30 minutes earlier. Over time, as this process is repeated, patients spend greater amounts of time sleeping while in bed.

Sleep restriction creates a degree of sleep deprivation that may enhance sleep onset and maintenance. Caution patients not to drive or perform hazardous activities while sleep-deprived.

8 Has the patient been prescribed appropriate doses of medications with appropriate indications?

Chronic insomnia sufferers often try to get more sleep by using alcohol, food supplement remedies, and OTC antihistamine sleep aids—none of which has demonstrated efficacy for treating insomnia. Although sedating prescription medications may be recommended for comorbid conditions, many also are prescribed off-label to promote sleep.

Examples include sedating antidepressants, antipsychotics, antihistamines, anticonvulsants, and benzodiazepines that are not indicated for insomnia. Little or no evidence supports these medications as safe and efficacious for treating insomnia, and important safety concerns are associated with their use.

The BZRA category includes 5 benzodiazepines and 4 nonbenzodiazepine formulations. Half-lives vary from approximately 1 hour to several days. Compared with benzodiazepines, nonbenzodiazepines have greater selectivity for GABAA receptor complexes incorporating the alpha-1 sub-unit subtype, which may confer some safety and tolerability advantages. One extended-release formulation is available. All may be beneficial for sleep onset, and some have indications for sleep maintenance difficulty.

Ramelteon is a nonsedating selective melatonin receptor agonist approved for treating insomnia characterized by sleep onset difficulty. This agent—which attenuates evening circadian arousal—may help promote sleep onset and enhance sleep during the early part of the night.

Administration. Inadequate dosing of insomnia medications may cause treatment to fail, but prescribing beyond approved ranges is rarely necessary. High sedative doses increase the risk of adverse effects, and patients may sleep no better. Adverse effects may include somnolence, headache, dizziness, nausea, diarrhea, and anterograde amnesia. Rarely patients may exhibit sleep walking or confused behaviors within a few hours after taking a hypnotic dose.

Recommendation. Customize your selection of FDA-approved insomnia medications. Consider whether your patient needs medication for sleep onset or sleep maintenance. In most cases, prescribe within dosing ranges listed in Table 3

Table 3

Insomnia treatment: FDA-approved medications

Related Resources

• American Academy of Sleep Medicine. www.aasmnet.org.
  
• National Sleep Foundation. www.sleepfoundation.org.
  
• NIH National Center for Sleep Disorders Research. www.nhlbi.nih.gov/about/ncsdr.
  

Drug brand names

• Estazolam • ProSom
  
• Eszopiclone • Lunesta
  
• Flurazepam • Dalmane
  
• Quazepam • Doral
  
• Ramelteon • Rozerem
  
• Temazepam • Restoril
  
• Triazolam • Halcion
  
• Zaleplon • Sonata
  
• Zolpidem • Ambien
  
• Zolpidem ER • Ambien CR
  

Disclosure

Dr. Neubauer is a consultant to Neurocrine Biosciences, sanofi-aventis, and Takeda Pharmaceuticals North America and a speaker for sanofi-aventis and Takeda Pharmaceuticals North America.