Current Psychiatry

Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.

Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.

CHARTING DREAM SEQUENCES

The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.¹

Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories² than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.

Dreams’ emotional tone tends to shift from negative to positive as the night goes on:³

• Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
• Conversely, a dream sequence may show no progress within the night⁴—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.

This “sequential hypothesis”⁵ holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.

Figure REM sleep: Dreaming’s prime time

CASE EXAMPLE: NIGHTMARES FOR 13 YEARS

Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.

Her therapist gives Ms. R four rules—the RISC method⁶—for shifting her dreams from negative to positive:

• Recognize that the dream is not going well.
• Identify what about it is frightening.
• Stop the dream, even if she must force her eyes open.
• Change the action to something positive.

At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.

After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.

CLINICAL USES OF DREAM THERAPY

Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:

• Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.⁷
• Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.⁸
• Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.⁹

Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.

After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.⁵ Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.

Box

WHAT TURNED US OFF ABOUT DREAMS

Prolonged therapy. Freud’s The Interpretation of Dreams ¹⁰ was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.

From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson¹¹ suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”

In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.

Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.^12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.

After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis¹⁴ wiped out dream research funding.

Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.¹⁵

Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.

WHAT BROUGHT DREAMS BACK

Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.

Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,¹⁶ for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.

Neuropsychological testing. Solms² used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.

COMING SOON: AT-HOME SLEEP MONITORS

In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.^17-19 This cumbersome and expensive procedure is being simplified for home use.

Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,^20,21 can easily record three or four dreams each night.

Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.

What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.

Related resources

• Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
• American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.

Disclosures

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

Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.

Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.

CHARTING DREAM SEQUENCES

The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.¹

Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories² than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.

Dreams’ emotional tone tends to shift from negative to positive as the night goes on:³

• Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
• Conversely, a dream sequence may show no progress within the night⁴—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.

This “sequential hypothesis”⁵ holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.

Figure REM sleep: Dreaming’s prime time

CASE EXAMPLE: NIGHTMARES FOR 13 YEARS

Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.

Her therapist gives Ms. R four rules—the RISC method⁶—for shifting her dreams from negative to positive:

• Recognize that the dream is not going well.
• Identify what about it is frightening.
• Stop the dream, even if she must force her eyes open.
• Change the action to something positive.

At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.

After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.

CLINICAL USES OF DREAM THERAPY

Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:

• Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.⁷
• Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.⁸
• Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.⁹

Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.

After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.⁵ Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.

Box

WHAT TURNED US OFF ABOUT DREAMS

Prolonged therapy. Freud’s The Interpretation of Dreams ¹⁰ was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.

From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson¹¹ suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”

In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.

Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.^12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.

After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis¹⁴ wiped out dream research funding.

Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.¹⁵

Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.

WHAT BROUGHT DREAMS BACK

Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.

Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,¹⁶ for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.

Neuropsychological testing. Solms² used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.

COMING SOON: AT-HOME SLEEP MONITORS

In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.^17-19 This cumbersome and expensive procedure is being simplified for home use.

Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,^20,21 can easily record three or four dreams each night.

Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.

What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.

Related resources

• Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
• American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.

Disclosures

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

Dreams are a rich resource for understanding how the mind integrates waking experience into older memory networks. Any psychiatrist who doubts dreams’ therapeutic value has probably not attended closely to his or her own dreams or become aware of exciting new evidence.

Recent understandings of how memory is processed during sleep are bringing dreams back into clinical importance. Patients can gather clinically useful data while sleeping—not in laboratories but in their own beds. Detecting and interpreting patterns in that data can help you treat patients not responding adequately to other therapies.

CHARTING DREAM SEQUENCES

The rate at which the eyes move during rapid-eye movement (REM) sleep (Figure) has been associated with memory consolidation. Eye movements increase during REM sleep, and waking performance improves after intensive learning periods. When eye movements are sparse, patients report dreams with less visual imagery and blander emotional content.¹

Though all sleep stages contribute to learning and memory, REM sleep appears to allow wider, easier access to memories² than does slow-wave sleep or waking. In other words, dreams are far from meaningless. They constitute a continuing mental operation that allows us to modify memory networks of emotional importance to us.

Dreams’ emotional tone tends to shift from negative to positive as the night goes on:³

• Dream-to-dream down-regulation of negative feelings is seen when a person’s waking concerns are strong but not overwhelming.
• Conversely, a dream sequence may show no progress within the night⁴—and the last dream may be as negative as the first—if the person has reached a point of resignation while awake.

This “sequential hypothesis”⁵ holds that knowledge of dreams as they occur—one after the other within the night—is a valuable resource for observing how a person is relating waking experience to the past. Dreams thus can give the therapist a “heads up” about a patient’s progress in organizing troublesome feelings.

Figure REM sleep: Dreaming’s prime time

CASE EXAMPLE: NIGHTMARES FOR 13 YEARS

Ms. R, a newlywed at age 30, presents for help with repetitive nightmares that prevent her from sharing a bed with her husband. She was raped at age 17 and has suffered nightmares since then. Once or more nightly she dreams of being attacked and awakens in terror, with profuse sweating. She usually has to change her nightclothes and sometimes the sheets.

Her therapist gives Ms. R four rules—the RISC method⁶—for shifting her dreams from negative to positive:

• Recognize that the dream is not going well.
• Identify what about it is frightening.
• Stop the dream, even if she must force her eyes open.
• Change the action to something positive.

At the third therapy session, Ms. R reports she had a successful dream. She was lying on her back on an open elevator platform. The elevator was rising dangerously high over the cityscape. She realized she was afraid and got up to see what was happening. As she arose, the elevator walls rose up to protect her. The patient says she learned if she “stands up for herself” all would be well.

After two more sessions with successful practice of this skill, she terminates therapy. When called 1 year later, she says she is expecting a child and has only an occasional nightmare, which she feels she can handle.

CLINICAL USES OF DREAM THERAPY

Dream interpretation may help us understand emotional programs that underlie patients’ unsatisfactory waking behavior. For example:

• Victims of posttraumatic stress disorder (PTSD) such as Ms. R may suffer repetitive nightmares with recurrent themes and excessive negative feelings. We can encourage them to shift their dream scripts from negative to positive.⁷
• Uninsightful, alexythymic patients, who often leave treatment before deriving any benefit, may learn to understand themselves by becoming aware of their dreams.⁸
• Severely depressed patientsoften have limited dream recall during sleep studies—even when every REM period is interrupted. They may be taught to improve their dream recall.⁹

Rules for improving dream recall are few, simple, and effective when the sleeper is motivated to remember them (Box). Just as one can learn to awaken before the morning alarm clock goes off, patients can learn to awaken to recall a dream.

After you have enough of a patient’s dreams to work from—20 is a good start—look for repeated dimensions that are the dreams’ building blocks.⁵ Look for polar opposites—such as safe-at risk, foolish-clever, exposed-hidden, strong-weak, attractive-ugly—that describe major characteristics of the self figure. Each has a positive or negative emotional value that can be explored.

Box

WHAT TURNED US OFF ABOUT DREAMS

Prolonged therapy. Freud’s The Interpretation of Dreams ¹⁰ was a major influence on how therapists used dreams to understand their patients in the early 20th century. Freud concluded that dreams —however strange—represent hallucinated fulfillment of repressed early wishes and tie up psychic energy to conceal unacceptable desires.

From this point of view, dreams provide a road map to understand persistent, nonrational, sometimes self-defeating behaviors that bring patients to therapy. The map, however, was more maze than speedway, full of detours and requiring much time to navigate the boulevards of associations that lead from one dream element to the next. Erik Erickson¹¹ suggested that dreams fell into disuse as therapeutic tools in the 1930s because psychoanalysis in general—and dream interpretation in particular—did not fit the American value of “the faster the better.”

In retrospect, the unconscious mind’s defenses may not have been what prolonged efforts to understand dream meaning. Rather, it may have been that the analyst had to work from whatever scraps the patient could remember of past dreams, to say nothing of new ones that occurred since the last appointment. That one dream could occupy many treatment hours did not trouble the Freudians, however, as—they argued—any-thing the patient does remember is proof of its importance.

Sleep research dealt the worst blow to the pursuit of dreams’ meaning and function.^12,13 Contrary to Freud’s view, dreams are not elusive if caught in the act. They can be reliably retrieved from REM episodes, which occur three to five times nightly with great regularity.

After REM sleep was found to initiate from the “unthinking pons,” dreams were proclaimed to have no inherent meaning worthy of serious effort. At best, they were explained as the result of random stimuli producing images to which we add meaning as we awaken. Thus, they offer no unique contribution to understanding psychic life. This “activation-synthesis” hypothesis¹⁴ wiped out dream research funding.

Medications. The pharmacologic revolution allowed more-rapid relief of anxiety and depression symptoms than did dream interpretation. Clinicians may feel that “we can forget about dreams because we now have better options.” This ignores research showing that psychiatric medication plus psychotherapy is more effective for a longer time than either alone.¹⁵

Evidence-based medicine. Dream content is inherently subjective and not open to objective observation, the heart of scientific methods. Only the dreamer can say what was dreamed.

WHAT BROUGHT DREAMS BACK

Better methods and more-sophisticated models renewed dream interpretation as a useful adjunct to other psychotherapies. In addition to research in memory processing, imaging methods and neuropsychological testing have changed our understanding of brain activity during sleep.

Brain imaging. Early sleep study was limited to recordings from the scalp surface. Now positron emission tomography and functional magnetic imagery allow researchers to see changes in brain activity and to study patterns during waking, non-REM sleep, and REM sleep and among clinical groups. Nofzinger et al,¹⁶ for example, showed differences in areas of high and low brain activation in persons with major depression, compared with normal controls.

Neuropsychological testing. Solms² used neuropsychological testing and interviewing to identify waking cognitive deficits and changes in dream experience in persons with brain damage from surgery or accident. Contrary to the “activation-synthesis” model, he concluded that dreams “are both generated and represented by some of the highest mental mechanisms.” He also argued that although dreams often coincide with the REM state, they also occur beyond REM.

COMING SOON: AT-HOME SLEEP MONITORS

In a sleep laboratory, awakening sleepers during REM periods and asking them to tell what they remember is the classic method for examining the relation among a night’s dreams.^17-19 This cumbersome and expensive procedure is being simplified for home use.

Computer-linked monitors are being developed that awaken the sleeper after a pre-set number of rapid eye movements and start a tape recorder to which the person can tell his or her dream. This system, which preserves the dream story from memory loss or distortion,^20,21 can easily record three or four dreams each night.

Translating this sensory data into verbal reports remains difficult. Although repeated elements give clues to dream structure, a repeated theme within a night might be an artifact induced by waking the sleeper to ask for a report. If a sleeper reports dreaming about being in an accident, for example, he may be influenced to continue that line of thought as he is falling back to sleep. This, in turn, may influence the next dream.

What else can we do? Because dream recall is ephemeral at best, patients may need training before a therapist has a sample large enough to extract repeating elements and be confident of its reliability.

Related resources

• Schneider A, Domhoff GW. Psychology department, University of California, Santa Cruz. Web site for collecting dream reports. www.DreamBank.net.
• American Psychological Association. Dreaming. Quarterly multidisciplinary journal. www.apa.org/journals/drm/.

Disclosures

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

HISTORY: ‘THEY’RE TRYING TO KILL ME’

For the past 7 months Ms. G, age 47, has had worsening paranoid thoughts and sleep disturbances. She sleeps 4 hours or less a night, and her appetite and energy are diminished.

Her mother reports that Ms. G, who lives in an extended-care facility, believes the staff has injected embalming fluid into her body and is plotting to kill her. She says her daughter also has “fits” during which she hears a deafening noise that sounds like a vacuum cleaner, followed by a feeling of being pushed to the ground. Ms. G tells us that someone or something invisible is trying to control her.

Ms. G was diagnosed 2 years ago as having Parkinson’s disease and has chronically high liver transaminase enzymes. She also has moderate mental retardation secondary to cerebral palsy. She fears she will be harmed if she stays at the extendedcare facility, but we find no evidence that she has been abused or mistreated there.

Three months before presenting to us, Ms. G was hospitalized for 3 days to treat symptoms that suggested neuroleptic malignant syndrome (NMS) but were apparently caused by her inadvertently stopping her antiparkinson agents.

One month later, Ms. G was hospitalized again, this time for acute psychosis. Quetiapine, which she had been taking for antiparkinson medication-induced psychosis, was increased from 100 mg nightly to 75 mg bid, with reportedly good effect.

Shortly afterward, however, Ms. G’s paranoia worsened. At the facility, she has called 911 several times to report imagined threats from staff members. After referral from her primary care physician, we evaluate Ms. G and admit her to the adult inpatient psychiatric unit.

At intake, Ms. G is anxious and uncomfortable with notable muscle spasticity and twitching of her arms and legs. Mostly wheelchair-bound, she has longstanding physical abnormalities (shuffling gait; dystonia; drooling; slowed, dysarthric speech) secondary to comorbid Parkinson’s and cerebral palsy. She is agitated at first but grows calmer and cooperative.

Mental status examination shows a disorganized, tangential thought process and evidence of paranoid delusions and auditory hallucinations, but she denies visual hallucinations. She has poor insight into her illness but is oriented to time, place, and person. She can recall two of three objects after 3 minutes of distraction. Attention and concentration are intact.

Ms. G denies depressed mood, anhedonia, mania, or suicidal or homicidal thoughts. Her mother says no stressors other than the imagined threats to her life have affected her daughter.

The patient ’s temperature at admission is 98.0°F, her pulse is 108 beats per minute, and her blood pressure is 150/88 mm Hg. Laboratory workup shows a white blood cell count of 10,100/mm³ (normal range: 4,000 to 10,000/mm³), sodium level of 132 mEq/L (normal range: 135 to 145 mEq/L), and aspartate (AST) and alanine (ALT) transaminase levels of 611 U/L and 79 U/L, respectively (normal range for each: 0 to 35 U/L).

Aside from quetiapine, Ms. G also has been taking carbidopa/levodopa, seven 25/100-mg tablets daily, and pramipexole, 3 mg/d, for parkinsonism; citalopram, 20 mg/d, for depression; trazodone, 300 mg nightly, and lorazepam, 0.5 mg nightly, for insomnia; lopressor, 25 mg every 12 hours, for hypertension; and tolterodine, 1 mg bid, for urinary incontinence.

The authors’ observations

Parkinsonism typically responds to dopaminergic treatment. Excess dopamine agonism is believed to contribute to medication-induced psychosis, a common and often disabling complication of Parkinson’s disease^1,2 that often necessitates nursing home placement and may increase mortality.^2,3

Paranoia occurs in approximately 8% of patients treated for drug-induced Parkinson’s psychosis, and hallucinations (typically visual) may occur in as many as 30%.² Quetiapine, 50 to 225 mg/d, is considered a good first-line treatment for psychosis in Parkinson’s, although the agent has been tested for this use only in open-label trials.^2,3

Mental retardation and pre-existing parkinsonism, however, may increase Ms. G’s risk for NMS, a rare but potentially fatal reaction to antipsychotics believed to be caused by a sudden D₂ dopamine receptor blockade.^4,5 Signs include autonomic instability, extrapyramidal symptoms, hyperpyrexia, and altered mental status.

Of 68 patients with NMS studied by Ananth et al,⁴ 13.2% were mentally retarded, and uncontrolled studies⁶ have proposed mental retardation as a potential risk factor (Table 1). A 2003 case control study⁶ found a higher incidence of NMS among mentally retarded patients than among nonretarded persons, but the difference was not statistically significant. There are no known links between specific causes of mental retardation and NMS.

Even so, Ms. G’s psychosis is compromising her already diminished quality of life. We will increase her quetiapine dosage slightly and watch for early signs of NMS, including fever, confusion, and increased muscle rigidity.

Table 1

Factors that increase risk of neuroleptic malignant syndrome*

TREATMENT: MEDICATION CHANGE

Upon admission, quetiapine is increased to 75 mg in the morning and 125 mg at bedtime—still well below the dosage at which quetiapine increases the risk of NMS (Table 2). Trazodone is decreased to 100 mg/d because of quetiapine’s sedating properties. Citalopram and tolterodine are stopped for fear that either agent would aggravate her psychosis. We continue all other drugs as previously prescribed. Her paranoia begins to subside.

Three days later, Ms. G’s is increasingly confused and agitated, and her temperature rises to 101.3°F. Physical exam shows increased muscle rigidity. She is given lorazepam, 1 mg, and transferred to the emergency room for evaluation.

In the ER, Ms. G’s temperature rises to 102.3°F. Other vital signs include:

• heart rate, 112 to 120 beats per minute
  
• respiratory rate, 18 to 20 breaths per minute
  
• oxygen saturation, 98% in room air
  
• blood pressure, 131/61 mm Hg while seated and 92/58 mm Hg while standing.
  

CNS or systemic infection and myocardial infarction are considered less likely because of her reactive pupils, lack of nuchal rigidity, troponin 3. Additionally, CSF shows normal glucose and protein levels, ALT and AST are 217 and 261 U/L, respectively, and chest x-ray shows no acute cardiopulmonary abnormality.

Ms. G is admitted to the medical intensive care unit and given IV fluids. All psychotropic and antiparkinson medications are stopped for 12 hours. Ms. G is then transferred to the general medical service for continued observation and IV hydration.

Six hours later, lorazepam, 0.5 mg every 8 hours, is resumed to control Ms. G’s anxiety. Carbidopa/levodopa is resumed at the previous dosage; all other medications remain on hold.

Renal damage is not apparent, but repeat chest x-ray taken 2 days after admission to the ER shows right middle lobe pneumonia, which resolved with antibiotics.

Six days after entering the medical unit, Ms. G is no longer agitated or paranoid. She is discharged that day and continued on lorazepam, 1 mg every 8 hours as needed to control her anxiety and prevent paranoia, and carbidopa/levidopa 8-¹/₂ 25/100-mg tablets daily for her parkinsonism. Trazodone, 100 mg nightly, is continued for 3 days to help her sleep, as is amoxicillin/clavulanate, 500 mg every 8 hours, in case an underlying infection exists. Quetiapine, citalopram, and tolterodine are discontinued; all other medications are resumed as previously prescribed.

Table 2

Antipsychotic-related NMS risk increases at these dosages

The authors’ observations

Ms. G’s NMS symptoms surfaced 3 days after her quetiapine dosage was increased, suggesting that the antipsychotic may have caused this episode.

We ruled out antiparkinson agent withdrawal malignant syndrome—usually caused by abrupt cessation of Parkinson’s medications. Ms. G’s carbidopa/levodopa had not been adjusted before the symptoms emerged, and she did not worsen after the agent was stopped temporarily. Her brief pneumonia episode, however, could have caused symptoms that mimicked this withdrawal syndrome.

Antiparkinson agent withdrawal malignant syndrome symptoms resemble those of NMS.^9,10 Worsening parkinsonism, dehydration, and infection increase the risk.¹⁰ Some research suggests that leukocytosis or elevated inflammation-related cytokines may accelerate withdrawal syndrome.¹⁰

The authors’ observations

Ms. G’s case illustrates the difficulty of treating psychosis in a patient at risk for NMS.

Of the 68 patients in the Ananth et al study with atypical antipsychotic-induced NMS, 11 were rechallenged after an NMS episode with the same agent and 8 were switched to another atypical. NMS recurred in 4 of these 19 patients.⁴

Ms. G was stable on lorazepam at discharge, but we would consider rechallenging with quetiapine or another antipsychotic if necessary. NMS recurs in 30% to 50%¹¹ of patients after antipsychotic rechallenge, but waiting 2 weeks to resume antipsychotic therapy appears to reduce this risk.¹² Benzodiazepines and electroconvulsive therapy are acceptable—though unproven—second-line therapies if antipsychotic rechallenge is deemed too risky,^11,13 such as in some patients with a previous severe NMS episode; evidence of stroke, Parkinson’s or other neurodegenerative disease; or multiple acute medical problems.

CONTINUED TREATMENT: A RELAPSE

Three months later, Ms. G is readmitted to the neurology service for 3 weeks after being diagnosed with elevated CK, possibly caused by NMS or rhabdomyolysis secondary to persistent dyskinesia. We believe an inadvertent decrease in her carbidopa/levodopa caused the episode, as she had taken no neuroleptics between hospitalizations.

Ms. G is discharged on quetiapine, 25 mg nightly, along with her other medications. Her current psychiatric and neurologic status is unknown.

The authors’ observations

Detecting NMS symptoms early is critical to preventing mortality. Although NMS risk with atypical and typical antipsychotics is similar,⁴ fewer deaths from NMS have been reported after use of atypicals (3 deaths among 68 cases) than typical neuroleptics (30% mortality rate in the 1960s and 70s, and 10% mortality from 1980-87).¹⁴ Earlier recognition and treatment may be decreasing NMS-related mortality.⁴

Consider NMS in the differential diagnosis when the patient’s mental status changes.

Related resources

• Emedicine: Neuroleptic malignant syndrome. www.emedicine.com/med/topic2614.htm.
  
• Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin 2004;22:389-411.
  
• Susman VL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q 2001;72:325-36.
  

• Amoxicillin/clavulanate • Augmentin
  
• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Sinemet
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Lopressor • Toprol
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Pramipexole • Mirapex
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Tolterodine • Detrol
  
• Trazodone • Desyrel
  
• Ziprasidone • Geodon
  

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

Acknowledgments

The authors wish to thank Robert B. Milstein, MD, PhD, and Benjamin Zigun, MD, JD, for their help in preparing this article for publication.

This project is supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant number 1 K01 HP 00071-02 and Geriatric Academic Career Award ($58,009). The content and conclusion are those of Dr. Tampi and are not the official position or policy of, nor should be any endorsements be inferred by, the Bureau of Health Professions, HRSA, DHHS or the United States Government.

HISTORY: ‘THEY’RE TRYING TO KILL ME’

For the past 7 months Ms. G, age 47, has had worsening paranoid thoughts and sleep disturbances. She sleeps 4 hours or less a night, and her appetite and energy are diminished.

Her mother reports that Ms. G, who lives in an extended-care facility, believes the staff has injected embalming fluid into her body and is plotting to kill her. She says her daughter also has “fits” during which she hears a deafening noise that sounds like a vacuum cleaner, followed by a feeling of being pushed to the ground. Ms. G tells us that someone or something invisible is trying to control her.

Ms. G was diagnosed 2 years ago as having Parkinson’s disease and has chronically high liver transaminase enzymes. She also has moderate mental retardation secondary to cerebral palsy. She fears she will be harmed if she stays at the extendedcare facility, but we find no evidence that she has been abused or mistreated there.

Three months before presenting to us, Ms. G was hospitalized for 3 days to treat symptoms that suggested neuroleptic malignant syndrome (NMS) but were apparently caused by her inadvertently stopping her antiparkinson agents.

One month later, Ms. G was hospitalized again, this time for acute psychosis. Quetiapine, which she had been taking for antiparkinson medication-induced psychosis, was increased from 100 mg nightly to 75 mg bid, with reportedly good effect.

Shortly afterward, however, Ms. G’s paranoia worsened. At the facility, she has called 911 several times to report imagined threats from staff members. After referral from her primary care physician, we evaluate Ms. G and admit her to the adult inpatient psychiatric unit.

At intake, Ms. G is anxious and uncomfortable with notable muscle spasticity and twitching of her arms and legs. Mostly wheelchair-bound, she has longstanding physical abnormalities (shuffling gait; dystonia; drooling; slowed, dysarthric speech) secondary to comorbid Parkinson’s and cerebral palsy. She is agitated at first but grows calmer and cooperative.

Mental status examination shows a disorganized, tangential thought process and evidence of paranoid delusions and auditory hallucinations, but she denies visual hallucinations. She has poor insight into her illness but is oriented to time, place, and person. She can recall two of three objects after 3 minutes of distraction. Attention and concentration are intact.

Ms. G denies depressed mood, anhedonia, mania, or suicidal or homicidal thoughts. Her mother says no stressors other than the imagined threats to her life have affected her daughter.

The patient ’s temperature at admission is 98.0°F, her pulse is 108 beats per minute, and her blood pressure is 150/88 mm Hg. Laboratory workup shows a white blood cell count of 10,100/mm³ (normal range: 4,000 to 10,000/mm³), sodium level of 132 mEq/L (normal range: 135 to 145 mEq/L), and aspartate (AST) and alanine (ALT) transaminase levels of 611 U/L and 79 U/L, respectively (normal range for each: 0 to 35 U/L).

Aside from quetiapine, Ms. G also has been taking carbidopa/levodopa, seven 25/100-mg tablets daily, and pramipexole, 3 mg/d, for parkinsonism; citalopram, 20 mg/d, for depression; trazodone, 300 mg nightly, and lorazepam, 0.5 mg nightly, for insomnia; lopressor, 25 mg every 12 hours, for hypertension; and tolterodine, 1 mg bid, for urinary incontinence.

The authors’ observations

Parkinsonism typically responds to dopaminergic treatment. Excess dopamine agonism is believed to contribute to medication-induced psychosis, a common and often disabling complication of Parkinson’s disease^1,2 that often necessitates nursing home placement and may increase mortality.^2,3

Paranoia occurs in approximately 8% of patients treated for drug-induced Parkinson’s psychosis, and hallucinations (typically visual) may occur in as many as 30%.² Quetiapine, 50 to 225 mg/d, is considered a good first-line treatment for psychosis in Parkinson’s, although the agent has been tested for this use only in open-label trials.^2,3

Mental retardation and pre-existing parkinsonism, however, may increase Ms. G’s risk for NMS, a rare but potentially fatal reaction to antipsychotics believed to be caused by a sudden D₂ dopamine receptor blockade.^4,5 Signs include autonomic instability, extrapyramidal symptoms, hyperpyrexia, and altered mental status.

Of 68 patients with NMS studied by Ananth et al,⁴ 13.2% were mentally retarded, and uncontrolled studies⁶ have proposed mental retardation as a potential risk factor (Table 1). A 2003 case control study⁶ found a higher incidence of NMS among mentally retarded patients than among nonretarded persons, but the difference was not statistically significant. There are no known links between specific causes of mental retardation and NMS.

Even so, Ms. G’s psychosis is compromising her already diminished quality of life. We will increase her quetiapine dosage slightly and watch for early signs of NMS, including fever, confusion, and increased muscle rigidity.

Table 1

Factors that increase risk of neuroleptic malignant syndrome*

TREATMENT: MEDICATION CHANGE

Upon admission, quetiapine is increased to 75 mg in the morning and 125 mg at bedtime—still well below the dosage at which quetiapine increases the risk of NMS (Table 2). Trazodone is decreased to 100 mg/d because of quetiapine’s sedating properties. Citalopram and tolterodine are stopped for fear that either agent would aggravate her psychosis. We continue all other drugs as previously prescribed. Her paranoia begins to subside.

Three days later, Ms. G’s is increasingly confused and agitated, and her temperature rises to 101.3°F. Physical exam shows increased muscle rigidity. She is given lorazepam, 1 mg, and transferred to the emergency room for evaluation.

In the ER, Ms. G’s temperature rises to 102.3°F. Other vital signs include:

• heart rate, 112 to 120 beats per minute
  
• respiratory rate, 18 to 20 breaths per minute
  
• oxygen saturation, 98% in room air
  
• blood pressure, 131/61 mm Hg while seated and 92/58 mm Hg while standing.
  

CNS or systemic infection and myocardial infarction are considered less likely because of her reactive pupils, lack of nuchal rigidity, troponin 3. Additionally, CSF shows normal glucose and protein levels, ALT and AST are 217 and 261 U/L, respectively, and chest x-ray shows no acute cardiopulmonary abnormality.

Ms. G is admitted to the medical intensive care unit and given IV fluids. All psychotropic and antiparkinson medications are stopped for 12 hours. Ms. G is then transferred to the general medical service for continued observation and IV hydration.

Six hours later, lorazepam, 0.5 mg every 8 hours, is resumed to control Ms. G’s anxiety. Carbidopa/levodopa is resumed at the previous dosage; all other medications remain on hold.

Renal damage is not apparent, but repeat chest x-ray taken 2 days after admission to the ER shows right middle lobe pneumonia, which resolved with antibiotics.

Six days after entering the medical unit, Ms. G is no longer agitated or paranoid. She is discharged that day and continued on lorazepam, 1 mg every 8 hours as needed to control her anxiety and prevent paranoia, and carbidopa/levidopa 8-¹/₂ 25/100-mg tablets daily for her parkinsonism. Trazodone, 100 mg nightly, is continued for 3 days to help her sleep, as is amoxicillin/clavulanate, 500 mg every 8 hours, in case an underlying infection exists. Quetiapine, citalopram, and tolterodine are discontinued; all other medications are resumed as previously prescribed.

Table 2

Antipsychotic-related NMS risk increases at these dosages

The authors’ observations

Ms. G’s NMS symptoms surfaced 3 days after her quetiapine dosage was increased, suggesting that the antipsychotic may have caused this episode.

We ruled out antiparkinson agent withdrawal malignant syndrome—usually caused by abrupt cessation of Parkinson’s medications. Ms. G’s carbidopa/levodopa had not been adjusted before the symptoms emerged, and she did not worsen after the agent was stopped temporarily. Her brief pneumonia episode, however, could have caused symptoms that mimicked this withdrawal syndrome.

Antiparkinson agent withdrawal malignant syndrome symptoms resemble those of NMS.^9,10 Worsening parkinsonism, dehydration, and infection increase the risk.¹⁰ Some research suggests that leukocytosis or elevated inflammation-related cytokines may accelerate withdrawal syndrome.¹⁰

The authors’ observations

Ms. G’s case illustrates the difficulty of treating psychosis in a patient at risk for NMS.

Of the 68 patients in the Ananth et al study with atypical antipsychotic-induced NMS, 11 were rechallenged after an NMS episode with the same agent and 8 were switched to another atypical. NMS recurred in 4 of these 19 patients.⁴

Ms. G was stable on lorazepam at discharge, but we would consider rechallenging with quetiapine or another antipsychotic if necessary. NMS recurs in 30% to 50%¹¹ of patients after antipsychotic rechallenge, but waiting 2 weeks to resume antipsychotic therapy appears to reduce this risk.¹² Benzodiazepines and electroconvulsive therapy are acceptable—though unproven—second-line therapies if antipsychotic rechallenge is deemed too risky,^11,13 such as in some patients with a previous severe NMS episode; evidence of stroke, Parkinson’s or other neurodegenerative disease; or multiple acute medical problems.

CONTINUED TREATMENT: A RELAPSE

Three months later, Ms. G is readmitted to the neurology service for 3 weeks after being diagnosed with elevated CK, possibly caused by NMS or rhabdomyolysis secondary to persistent dyskinesia. We believe an inadvertent decrease in her carbidopa/levodopa caused the episode, as she had taken no neuroleptics between hospitalizations.

Ms. G is discharged on quetiapine, 25 mg nightly, along with her other medications. Her current psychiatric and neurologic status is unknown.

The authors’ observations

Detecting NMS symptoms early is critical to preventing mortality. Although NMS risk with atypical and typical antipsychotics is similar,⁴ fewer deaths from NMS have been reported after use of atypicals (3 deaths among 68 cases) than typical neuroleptics (30% mortality rate in the 1960s and 70s, and 10% mortality from 1980-87).¹⁴ Earlier recognition and treatment may be decreasing NMS-related mortality.⁴

Consider NMS in the differential diagnosis when the patient’s mental status changes.

Related resources

• Emedicine: Neuroleptic malignant syndrome. www.emedicine.com/med/topic2614.htm.
  
• Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin 2004;22:389-411.
  
• Susman VL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q 2001;72:325-36.
  

• Amoxicillin/clavulanate • Augmentin
  
• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Sinemet
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Lopressor • Toprol
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Pramipexole • Mirapex
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Tolterodine • Detrol
  
• Trazodone • Desyrel
  
• Ziprasidone • Geodon
  

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

Acknowledgments

The authors wish to thank Robert B. Milstein, MD, PhD, and Benjamin Zigun, MD, JD, for their help in preparing this article for publication.

This project is supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant number 1 K01 HP 00071-02 and Geriatric Academic Career Award ($58,009). The content and conclusion are those of Dr. Tampi and are not the official position or policy of, nor should be any endorsements be inferred by, the Bureau of Health Professions, HRSA, DHHS or the United States Government.

HISTORY: ‘THEY’RE TRYING TO KILL ME’

For the past 7 months Ms. G, age 47, has had worsening paranoid thoughts and sleep disturbances. She sleeps 4 hours or less a night, and her appetite and energy are diminished.

Her mother reports that Ms. G, who lives in an extended-care facility, believes the staff has injected embalming fluid into her body and is plotting to kill her. She says her daughter also has “fits” during which she hears a deafening noise that sounds like a vacuum cleaner, followed by a feeling of being pushed to the ground. Ms. G tells us that someone or something invisible is trying to control her.

Ms. G was diagnosed 2 years ago as having Parkinson’s disease and has chronically high liver transaminase enzymes. She also has moderate mental retardation secondary to cerebral palsy. She fears she will be harmed if she stays at the extendedcare facility, but we find no evidence that she has been abused or mistreated there.

Three months before presenting to us, Ms. G was hospitalized for 3 days to treat symptoms that suggested neuroleptic malignant syndrome (NMS) but were apparently caused by her inadvertently stopping her antiparkinson agents.

One month later, Ms. G was hospitalized again, this time for acute psychosis. Quetiapine, which she had been taking for antiparkinson medication-induced psychosis, was increased from 100 mg nightly to 75 mg bid, with reportedly good effect.

Shortly afterward, however, Ms. G’s paranoia worsened. At the facility, she has called 911 several times to report imagined threats from staff members. After referral from her primary care physician, we evaluate Ms. G and admit her to the adult inpatient psychiatric unit.

At intake, Ms. G is anxious and uncomfortable with notable muscle spasticity and twitching of her arms and legs. Mostly wheelchair-bound, she has longstanding physical abnormalities (shuffling gait; dystonia; drooling; slowed, dysarthric speech) secondary to comorbid Parkinson’s and cerebral palsy. She is agitated at first but grows calmer and cooperative.

Mental status examination shows a disorganized, tangential thought process and evidence of paranoid delusions and auditory hallucinations, but she denies visual hallucinations. She has poor insight into her illness but is oriented to time, place, and person. She can recall two of three objects after 3 minutes of distraction. Attention and concentration are intact.

Ms. G denies depressed mood, anhedonia, mania, or suicidal or homicidal thoughts. Her mother says no stressors other than the imagined threats to her life have affected her daughter.

The patient ’s temperature at admission is 98.0°F, her pulse is 108 beats per minute, and her blood pressure is 150/88 mm Hg. Laboratory workup shows a white blood cell count of 10,100/mm³ (normal range: 4,000 to 10,000/mm³), sodium level of 132 mEq/L (normal range: 135 to 145 mEq/L), and aspartate (AST) and alanine (ALT) transaminase levels of 611 U/L and 79 U/L, respectively (normal range for each: 0 to 35 U/L).

Aside from quetiapine, Ms. G also has been taking carbidopa/levodopa, seven 25/100-mg tablets daily, and pramipexole, 3 mg/d, for parkinsonism; citalopram, 20 mg/d, for depression; trazodone, 300 mg nightly, and lorazepam, 0.5 mg nightly, for insomnia; lopressor, 25 mg every 12 hours, for hypertension; and tolterodine, 1 mg bid, for urinary incontinence.

The authors’ observations

Parkinsonism typically responds to dopaminergic treatment. Excess dopamine agonism is believed to contribute to medication-induced psychosis, a common and often disabling complication of Parkinson’s disease^1,2 that often necessitates nursing home placement and may increase mortality.^2,3

Paranoia occurs in approximately 8% of patients treated for drug-induced Parkinson’s psychosis, and hallucinations (typically visual) may occur in as many as 30%.² Quetiapine, 50 to 225 mg/d, is considered a good first-line treatment for psychosis in Parkinson’s, although the agent has been tested for this use only in open-label trials.^2,3

Mental retardation and pre-existing parkinsonism, however, may increase Ms. G’s risk for NMS, a rare but potentially fatal reaction to antipsychotics believed to be caused by a sudden D₂ dopamine receptor blockade.^4,5 Signs include autonomic instability, extrapyramidal symptoms, hyperpyrexia, and altered mental status.

Of 68 patients with NMS studied by Ananth et al,⁴ 13.2% were mentally retarded, and uncontrolled studies⁶ have proposed mental retardation as a potential risk factor (Table 1). A 2003 case control study⁶ found a higher incidence of NMS among mentally retarded patients than among nonretarded persons, but the difference was not statistically significant. There are no known links between specific causes of mental retardation and NMS.

Even so, Ms. G’s psychosis is compromising her already diminished quality of life. We will increase her quetiapine dosage slightly and watch for early signs of NMS, including fever, confusion, and increased muscle rigidity.

Table 1

Factors that increase risk of neuroleptic malignant syndrome*

TREATMENT: MEDICATION CHANGE

Upon admission, quetiapine is increased to 75 mg in the morning and 125 mg at bedtime—still well below the dosage at which quetiapine increases the risk of NMS (Table 2). Trazodone is decreased to 100 mg/d because of quetiapine’s sedating properties. Citalopram and tolterodine are stopped for fear that either agent would aggravate her psychosis. We continue all other drugs as previously prescribed. Her paranoia begins to subside.

Three days later, Ms. G’s is increasingly confused and agitated, and her temperature rises to 101.3°F. Physical exam shows increased muscle rigidity. She is given lorazepam, 1 mg, and transferred to the emergency room for evaluation.

In the ER, Ms. G’s temperature rises to 102.3°F. Other vital signs include:

• heart rate, 112 to 120 beats per minute
  
• respiratory rate, 18 to 20 breaths per minute
  
• oxygen saturation, 98% in room air
  
• blood pressure, 131/61 mm Hg while seated and 92/58 mm Hg while standing.
  

CNS or systemic infection and myocardial infarction are considered less likely because of her reactive pupils, lack of nuchal rigidity, troponin 3. Additionally, CSF shows normal glucose and protein levels, ALT and AST are 217 and 261 U/L, respectively, and chest x-ray shows no acute cardiopulmonary abnormality.

Ms. G is admitted to the medical intensive care unit and given IV fluids. All psychotropic and antiparkinson medications are stopped for 12 hours. Ms. G is then transferred to the general medical service for continued observation and IV hydration.

Six hours later, lorazepam, 0.5 mg every 8 hours, is resumed to control Ms. G’s anxiety. Carbidopa/levodopa is resumed at the previous dosage; all other medications remain on hold.

Renal damage is not apparent, but repeat chest x-ray taken 2 days after admission to the ER shows right middle lobe pneumonia, which resolved with antibiotics.

Six days after entering the medical unit, Ms. G is no longer agitated or paranoid. She is discharged that day and continued on lorazepam, 1 mg every 8 hours as needed to control her anxiety and prevent paranoia, and carbidopa/levidopa 8-¹/₂ 25/100-mg tablets daily for her parkinsonism. Trazodone, 100 mg nightly, is continued for 3 days to help her sleep, as is amoxicillin/clavulanate, 500 mg every 8 hours, in case an underlying infection exists. Quetiapine, citalopram, and tolterodine are discontinued; all other medications are resumed as previously prescribed.

Table 2

Antipsychotic-related NMS risk increases at these dosages

The authors’ observations

Ms. G’s NMS symptoms surfaced 3 days after her quetiapine dosage was increased, suggesting that the antipsychotic may have caused this episode.

We ruled out antiparkinson agent withdrawal malignant syndrome—usually caused by abrupt cessation of Parkinson’s medications. Ms. G’s carbidopa/levodopa had not been adjusted before the symptoms emerged, and she did not worsen after the agent was stopped temporarily. Her brief pneumonia episode, however, could have caused symptoms that mimicked this withdrawal syndrome.

Antiparkinson agent withdrawal malignant syndrome symptoms resemble those of NMS.^9,10 Worsening parkinsonism, dehydration, and infection increase the risk.¹⁰ Some research suggests that leukocytosis or elevated inflammation-related cytokines may accelerate withdrawal syndrome.¹⁰

The authors’ observations

Ms. G’s case illustrates the difficulty of treating psychosis in a patient at risk for NMS.

Of the 68 patients in the Ananth et al study with atypical antipsychotic-induced NMS, 11 were rechallenged after an NMS episode with the same agent and 8 were switched to another atypical. NMS recurred in 4 of these 19 patients.⁴

Ms. G was stable on lorazepam at discharge, but we would consider rechallenging with quetiapine or another antipsychotic if necessary. NMS recurs in 30% to 50%¹¹ of patients after antipsychotic rechallenge, but waiting 2 weeks to resume antipsychotic therapy appears to reduce this risk.¹² Benzodiazepines and electroconvulsive therapy are acceptable—though unproven—second-line therapies if antipsychotic rechallenge is deemed too risky,^11,13 such as in some patients with a previous severe NMS episode; evidence of stroke, Parkinson’s or other neurodegenerative disease; or multiple acute medical problems.

CONTINUED TREATMENT: A RELAPSE

Three months later, Ms. G is readmitted to the neurology service for 3 weeks after being diagnosed with elevated CK, possibly caused by NMS or rhabdomyolysis secondary to persistent dyskinesia. We believe an inadvertent decrease in her carbidopa/levodopa caused the episode, as she had taken no neuroleptics between hospitalizations.

Ms. G is discharged on quetiapine, 25 mg nightly, along with her other medications. Her current psychiatric and neurologic status is unknown.

The authors’ observations

Detecting NMS symptoms early is critical to preventing mortality. Although NMS risk with atypical and typical antipsychotics is similar,⁴ fewer deaths from NMS have been reported after use of atypicals (3 deaths among 68 cases) than typical neuroleptics (30% mortality rate in the 1960s and 70s, and 10% mortality from 1980-87).¹⁴ Earlier recognition and treatment may be decreasing NMS-related mortality.⁴

Consider NMS in the differential diagnosis when the patient’s mental status changes.

Related resources

• Emedicine: Neuroleptic malignant syndrome. www.emedicine.com/med/topic2614.htm.
  
• Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin 2004;22:389-411.
  
• Susman VL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q 2001;72:325-36.
  

• Amoxicillin/clavulanate • Augmentin
  
• Aripiprazole • Abilify
  
• Carbidopa/levodopa • Sinemet
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Lopressor • Toprol
  
• Lorazepam • Ativan
  
• Olanzapine • Zyprexa
  
• Pramipexole • Mirapex
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Tolterodine • Detrol
  
• Trazodone • Desyrel
  
• Ziprasidone • Geodon
  

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

Acknowledgments

The authors wish to thank Robert B. Milstein, MD, PhD, and Benjamin Zigun, MD, JD, for their help in preparing this article for publication.

This project is supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant number 1 K01 HP 00071-02 and Geriatric Academic Career Award ($58,009). The content and conclusion are those of Dr. Tampi and are not the official position or policy of, nor should be any endorsements be inferred by, the Bureau of Health Professions, HRSA, DHHS or the United States Government.

Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).^1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.

For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:

• clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
  
• how to address comorbidities that pose acute danger or would prevent effective psychotherapy
  
• how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)^7-9—to also manage most comorbid disorders.
  

Table 1

Common psychiatric comorbidities with OCD

IS OCD PRIMARY?

OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.

Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.

To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.

ASSESSING OCD, COMORBID CONDITIONS

When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).^10-14

In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)¹⁵ or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)¹⁰ are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.

An alternative may be the Mini International Neuropsychiatric Interview (MINI).¹¹ The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.

Table 2

Common assessment tools for patients with suspected OCD

The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.^12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.

The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.¹⁶

TREATING UNCOMPLICATED OCD

CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.¹⁷ Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.¹⁸

In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,¹⁸ it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.¹⁹

Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.²⁰

Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.²¹ The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.

High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.

Table 3

Serotonin reuptake inhibitors indicated for treating OCD*

Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.²²

The up to 40% of patients who do not respond to SRI therapy require alternate strategies:

• Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.^23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
  
• The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.²⁵
  
• Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.²⁴
  

FACTORING IN COMORBIDITIES

Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.¹⁷

Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.

Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.

Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.²⁶ For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.¹⁷

Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.²⁷ Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.³

Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.²⁷ Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:

• constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
  
• instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
  

Related resources

• Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
  
• Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
  
• Obsessive-Compulsive Foundation. www.ocfoundation.org.
  

• Buspirone • BuSpar
  
• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  
• Venlafaxine • Effexor
  

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

Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).^1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.

For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:

• clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
  
• how to address comorbidities that pose acute danger or would prevent effective psychotherapy
  
• how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)^7-9—to also manage most comorbid disorders.
  

Table 1

Common psychiatric comorbidities with OCD

IS OCD PRIMARY?

OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.

Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.

To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.

ASSESSING OCD, COMORBID CONDITIONS

When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).^10-14

In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)¹⁵ or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)¹⁰ are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.

An alternative may be the Mini International Neuropsychiatric Interview (MINI).¹¹ The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.

Table 2

Common assessment tools for patients with suspected OCD

The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.^12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.

The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.¹⁶

TREATING UNCOMPLICATED OCD

CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.¹⁷ Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.¹⁸

In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,¹⁸ it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.¹⁹

Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.²⁰

Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.²¹ The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.

High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.

Table 3

Serotonin reuptake inhibitors indicated for treating OCD*

Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.²²

The up to 40% of patients who do not respond to SRI therapy require alternate strategies:

• Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.^23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
  
• The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.²⁵
  
• Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.²⁴
  

FACTORING IN COMORBIDITIES

Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.¹⁷

Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.

Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.

Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.²⁶ For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.¹⁷

Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.²⁷ Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.³

Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.²⁷ Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:

• constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
  
• instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
  

Related resources

• Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
  
• Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
  
• Obsessive-Compulsive Foundation. www.ocfoundation.org.
  

• Buspirone • BuSpar
  
• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  
• Venlafaxine • Effexor
  

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

Psychiatric comorbidities complicate the treatment of obsessive-compulsive disorder (OCD) and are much more the rule than the exception in clinical practice (Table 1).^1-6 Even so, surprisingly few studies have examined comorbidities’ effects on OCD treatment, and results have been mixed.

For the typical patient with obsessive-compulsive symptoms, we discuss our experience and evidence that supports:

• clinically useful tools to differentiate OCD from other obsessive and anxiety disorders
  
• how to address comorbidities that pose acute danger or would prevent effective psychotherapy
  
• how to modify first-line OCD treatments—cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs)^7-9—to also manage most comorbid disorders.
  

Table 1

Common psychiatric comorbidities with OCD

IS OCD PRIMARY?

OCD-like obsessive thoughts or repetitive behaviors may be evident in a number of psychiatric disorders. Distinguishing OCD from masquerading or co-occurring conditions is important because interventions can differ.

Patients with generalized anxiety disorder (GAD), for example, may experience ruminative, anxious thoughts that mimic obsessions. Somatoform conditions such as hypochondriasis or body dysmorphic disorder are characterized by intense preoccupation with illness or appearance, respectively. Repetitive or compulsive behaviors may be seen in impulse control or developmental disorders such as pathologic gambling, trichotillomania, and Asperger’s disorder.

To help differentiate OCD from these conditions, consider the function of a patient’s symptoms. In OCD, obsessions are experienced as ego-dystonic and generally cause great anxiety. OCD patients perform compulsive rituals to alleviate anxiety but do not gain pleasure from their actions. Contrast this with trichotillomania’s repetitive behavior—commonly experienced as pleasurable or gratifying—or with GAD’s ruminative thoughts—seen as ego-syntonic worries about real-life situations.

ASSESSING OCD, COMORBID CONDITIONS

When you suspect psychiatric comorbidity with OCD, an accurate and thorough assessment is key to successful treatment (Table 2).^10-14

In specialty OCD clinics, the Structured Clinical Interview for DSM-IV (SCID-IV)¹⁵ or Anxiety Disorders Interview Schedule for the DSM-IV (ADIS-IV)¹⁰ are routinely given to assess the most common comorbid conditions. In clinical practice, however, these instruments can take up to several hours to perform, especially for patients who meet criteria for several disorders.

An alternative may be the Mini International Neuropsychiatric Interview (MINI).¹¹ The MINI is a short, structured, diagnostic interview for DSM-IV and ICD-10 that takes about 15 minutes and screens for most conditions commonly comorbid with OCD. The MINI provides less-detailed information than the SCID-IV or the ADIS-IV but allows for a quick, accurate diagnosis while using a structured format.

Table 2

Common assessment tools for patients with suspected OCD

The Yale-Brown Obsessive Compulsive Scale (YBOCS) is widely used.^12,13 It includes a checklist of common obsessions and compulsions plus 10 items measuring interference with daily living, distress, resistance, control, and time spent on symptoms. Each item is scored from 0 to 4, for a total score of 0 to 40.

The YBOCS has good reliability and validity, is available in both clinician-rated and self-rated versions, and can be given repeatedly to measure treatment progress. A Children’s Yale-Brown Obsessive-Compulsive Scale (CYBOCS) is useful for patients ages 6 to 17.¹⁶

TREATING UNCOMPLICATED OCD

CBT. When OCD is not concurrent with another diagnosis, expert consensus guidelines recommend CBT as first-line treatment.¹⁷ Most patients treated with exposure and response prevention (ERP) therapy—the specialized CBT for reducing anxiety that triggers obsessive-compulsive symptoms—report reduced symptoms and often maintain those gains over time.¹⁸

In specialty clinics, patients frequently engage in intensive ERP (2 hours per day, 3 to 5 times per week for about 3 weeks). Although studies find excellent outcomes with intensive OCD treatment,¹⁸ it is not always practical or indicated (as in patients with moderate symptoms). Less-intensive protocols, such as biweekly sessions, have also shown promise in studies examining how session frequency affects treatment outcome.¹⁹

Many studies supporting ERP’s efficacy in OCD have included relatively homogenous samples under well-controlled conditions. Some investigations have also found good effects for ERP when including patients with complex treatment histories, concomitant pharmacotherapy, and comorbid conditions.²⁰

Medication. Functional imaging studies suggest that OCD results from dysregulation in the socalled “OCD circuit”—the orbitofrontal cortex, anterior cingulate, and caudate nucleus. In patients with OCD, metabolic activity in this region is increased at rest relative to controls, increases further with symptoms, and decreases after successful treatment.²¹ The serotonin hypothesis—which emerged from observation that OCD symptoms responded to serotonergic medications but not to noradrenergic ones—suggests serotonin system dysregulation in patients with OCD.

High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.

Table 3

Serotonin reuptake inhibitors indicated for treating OCD*

Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.²²

The up to 40% of patients who do not respond to SRI therapy require alternate strategies:

• Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.^23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
  
• The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.²⁵
  
• Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.²⁴
  

FACTORING IN COMORBIDITIES

Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.¹⁷

Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.

Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.

Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.²⁶ For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.¹⁷

Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.²⁷ Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.³

Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.²⁷ Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:

• constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
  
• instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
  

Related resources

• Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
  
• Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
  
• Obsessive-Compulsive Foundation. www.ocfoundation.org.
  

• Buspirone • BuSpar
  
• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  
• Venlafaxine • Effexor
  

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

At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?

This article answers those questions by addressing:

• clinical guidelines for diagnosing metabolic syndrome
• suggested intervals for monitoring at-risk patients
• strategies for managing metabolic abnormalities with lifestyle changes or medication.

CASE REPORT: 'FAT' AND FRUSTRATED

Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.

Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.

Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.

The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).

The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.

Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?

IMPLICATIONS OF METABOLIC SYNDROME

Patients with metabolic syndrome are at increased risk for:

• type 2 diabetes¹
• CVD²
• increased mortality from CVD and all causes.³

In a prospective study that followed 1,209 Finnish men over an average 11.4 years,⁴ men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.

DEFINING METABOLIC SYNDROME

Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.

According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:

• abdominal obesity
• insulin resistance
• high blood pressure
• elevated triglycerides
• below-normal HDL.

This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).⁵ The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.

Table 1

5 defined risk factors* for metabolic syndrome

MONITORING FREQUENCY

Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.⁶

Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).

Table 2

Suggested monitoring intervals for patients taking atypical antipsychotics*

MANAGING METABOLIC PROBLEMS

Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:

• weight management, weight control education, and promoting regular exercise and a healthy diet
• switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
• working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.

Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.

Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.⁷ Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.⁷

Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.

Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,² triglycerides,¹⁷ blood pressure,¹⁸ and hyperglycemia.¹⁹

In one prospective study,²⁰ 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.

Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:

• 43% had lower triglycerides than at baseline
• 16% had higher HDL cholesterol
• 38% had lower blood pressure
• 9% had improved fasting glucose
• 28% reduced their waist circumference.

Table 3

Interventions for specific metabolic complications

Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.

By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.²¹

In a prospective 12-month trial,²² 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.²²

Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).

Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.

Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.^23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).⁶

Table 4

Atypical antipsychotics and their propensity for causing metabolic abnormalities

Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).

Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.²⁵ Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).

CASE CONTINUED: 10 LBS IN 10 WEEKS

At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).

Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.

Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.

Related resources

• National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
• Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
• National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
• Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.

Drug brand names

• Aripiprazole • Abilify
• Clozapine • Clozaril
• Metformin • Glucophage
• Olanzapine • Zyprexa
• Orlistat • Xenical
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sibutramine • Meridia
• Ziprasidone • Geodon

Disclosure

Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.

At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?

This article answers those questions by addressing:

• clinical guidelines for diagnosing metabolic syndrome
• suggested intervals for monitoring at-risk patients
• strategies for managing metabolic abnormalities with lifestyle changes or medication.

CASE REPORT: 'FAT' AND FRUSTRATED

Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.

Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.

Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.

The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).

The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.

Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?

IMPLICATIONS OF METABOLIC SYNDROME

Patients with metabolic syndrome are at increased risk for:

• type 2 diabetes¹
• CVD²
• increased mortality from CVD and all causes.³

In a prospective study that followed 1,209 Finnish men over an average 11.4 years,⁴ men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.

DEFINING METABOLIC SYNDROME

Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.

According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:

• abdominal obesity
• insulin resistance
• high blood pressure
• elevated triglycerides
• below-normal HDL.

This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).⁵ The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.

Table 1

5 defined risk factors* for metabolic syndrome

MONITORING FREQUENCY

Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.⁶

Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).

Table 2

Suggested monitoring intervals for patients taking atypical antipsychotics*

MANAGING METABOLIC PROBLEMS

Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:

• weight management, weight control education, and promoting regular exercise and a healthy diet
• switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
• working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.

Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.

Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.⁷ Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.⁷

Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.

Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,² triglycerides,¹⁷ blood pressure,¹⁸ and hyperglycemia.¹⁹

In one prospective study,²⁰ 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.

Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:

• 43% had lower triglycerides than at baseline
• 16% had higher HDL cholesterol
• 38% had lower blood pressure
• 9% had improved fasting glucose
• 28% reduced their waist circumference.

Table 3

Interventions for specific metabolic complications

Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.

By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.²¹

In a prospective 12-month trial,²² 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.²²

Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).

Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.

Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.^23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).⁶

Table 4

Atypical antipsychotics and their propensity for causing metabolic abnormalities

Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).

Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.²⁵ Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).

CASE CONTINUED: 10 LBS IN 10 WEEKS

At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).

Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.

Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.

Related resources

• National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
• Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
• National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
• Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.

Drug brand names

• Aripiprazole • Abilify
• Clozapine • Clozaril
• Metformin • Glucophage
• Olanzapine • Zyprexa
• Orlistat • Xenical
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sibutramine • Meridia
• Ziprasidone • Geodon

Disclosure

Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.

At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?

This article answers those questions by addressing:

• clinical guidelines for diagnosing metabolic syndrome
• suggested intervals for monitoring at-risk patients
• strategies for managing metabolic abnormalities with lifestyle changes or medication.

CASE REPORT: 'FAT' AND FRUSTRATED

Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.

Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.

Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.

The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).

The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.

Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?

IMPLICATIONS OF METABOLIC SYNDROME

Patients with metabolic syndrome are at increased risk for:

• type 2 diabetes¹
• CVD²
• increased mortality from CVD and all causes.³

In a prospective study that followed 1,209 Finnish men over an average 11.4 years,⁴ men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.

DEFINING METABOLIC SYNDROME

Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.

According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:

• abdominal obesity
• insulin resistance
• high blood pressure
• elevated triglycerides
• below-normal HDL.

This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).⁵ The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.

Table 1

5 defined risk factors* for metabolic syndrome

MONITORING FREQUENCY

Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.⁶

Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).

Table 2

Suggested monitoring intervals for patients taking atypical antipsychotics*

MANAGING METABOLIC PROBLEMS

Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:

• weight management, weight control education, and promoting regular exercise and a healthy diet
• switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
• working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.

Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.

Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.⁷ Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.⁷

Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.

Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,² triglycerides,¹⁷ blood pressure,¹⁸ and hyperglycemia.¹⁹

In one prospective study,²⁰ 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.

Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:

• 43% had lower triglycerides than at baseline
• 16% had higher HDL cholesterol
• 38% had lower blood pressure
• 9% had improved fasting glucose
• 28% reduced their waist circumference.

Table 3

Interventions for specific metabolic complications

Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.

By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.²¹

In a prospective 12-month trial,²² 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.²²

Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).

Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.

Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.^23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).⁶

Table 4

Atypical antipsychotics and their propensity for causing metabolic abnormalities

Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).

Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.²⁵ Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).

CASE CONTINUED: 10 LBS IN 10 WEEKS

At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).

Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.

Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.

Related resources

• National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
• Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
• National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
• Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.

Drug brand names

• Aripiprazole • Abilify
• Clozapine • Clozaril
• Metformin • Glucophage
• Olanzapine • Zyprexa
• Orlistat • Xenical
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sibutramine • Meridia
• Ziprasidone • Geodon

Disclosure

Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.

Cognitive-behavioral therapy (CBT) can help patients cope with auditory hallucinations and reshape delusional beliefs to make the voices less frequent.¹ Use the following CBT methods alone or with medication.

1. Engage the patient by showing interest in the voices. Ask: “When did the voices start? Where are they coming from? Can you bring them on or stop them? Do they tell you to do things? What happens when you ignore them?”

2. Normalize the hallucination. List scientifically plausible “reasons for hearing voices,”² including sleep deprivation, isolation, dehydration and/or starvation, extreme stress, strong thoughts or emotions, fever and illness, and drug/alcohol use.

Ask which reasons might apply. Patients often agree with several explanations and begin questioning their delusional interpretations. Your list should include the possibility that the voices are real, but only if the patient initially believes this.

3. Suggest coping strategies, such as:

• humming or singing a song several times
• listening to music
• reading (forwards and backwards)
• talking with others
• exercise
• ignoring the voices
• medication (important to include).

Ask which methods worked previously and have patients build on that list, if possible.

If a patient hears command hallucinations, assess their acuity and decide whether he or she is likely to act on them before starting CBT.

4. Use in-session voices to teach coping strategies. Ask the patient to hum a song with you (“Happy Birthday” works well). If unsuccessful, try reading a paragraph together forwards or backwards. If the voices stop—even for 2 minutes—tell the patient that he or she has begun to control them.³ Have the patient practice these exercises at home and notice if the voices stop for longer periods.

5. Briefly explain the neurology behind the voices. PET scans have shown that auditory hallucinations activate brain areas that regulate hearing and speaking,⁴ suggesting that people talk or think to themselves while hearing voices.

When patients ask why they hear strange voices, explain that many voices are buried inside our memory. When people hear voices, the brain’s speech, hearing, and memory centers interact.⁵

That said, calling auditory hallucinations “voice-thoughts,” rather than “voices,” reduces stigma and reinforces an alternate explanation behind the delusion. As the patient begins to understand that hallucinations are related to dysfunctional thoughts, we can help correct them.

Cognitive-behavioral therapy (CBT) can help patients cope with auditory hallucinations and reshape delusional beliefs to make the voices less frequent.¹ Use the following CBT methods alone or with medication.

1. Engage the patient by showing interest in the voices. Ask: “When did the voices start? Where are they coming from? Can you bring them on or stop them? Do they tell you to do things? What happens when you ignore them?”

2. Normalize the hallucination. List scientifically plausible “reasons for hearing voices,”² including sleep deprivation, isolation, dehydration and/or starvation, extreme stress, strong thoughts or emotions, fever and illness, and drug/alcohol use.

Ask which reasons might apply. Patients often agree with several explanations and begin questioning their delusional interpretations. Your list should include the possibility that the voices are real, but only if the patient initially believes this.

3. Suggest coping strategies, such as:

• humming or singing a song several times
• listening to music
• reading (forwards and backwards)
• talking with others
• exercise
• ignoring the voices
• medication (important to include).

Ask which methods worked previously and have patients build on that list, if possible.

If a patient hears command hallucinations, assess their acuity and decide whether he or she is likely to act on them before starting CBT.

4. Use in-session voices to teach coping strategies. Ask the patient to hum a song with you (“Happy Birthday” works well). If unsuccessful, try reading a paragraph together forwards or backwards. If the voices stop—even for 2 minutes—tell the patient that he or she has begun to control them.³ Have the patient practice these exercises at home and notice if the voices stop for longer periods.

5. Briefly explain the neurology behind the voices. PET scans have shown that auditory hallucinations activate brain areas that regulate hearing and speaking,⁴ suggesting that people talk or think to themselves while hearing voices.

When patients ask why they hear strange voices, explain that many voices are buried inside our memory. When people hear voices, the brain’s speech, hearing, and memory centers interact.⁵

That said, calling auditory hallucinations “voice-thoughts,” rather than “voices,” reduces stigma and reinforces an alternate explanation behind the delusion. As the patient begins to understand that hallucinations are related to dysfunctional thoughts, we can help correct them.

Cognitive-behavioral therapy (CBT) can help patients cope with auditory hallucinations and reshape delusional beliefs to make the voices less frequent.¹ Use the following CBT methods alone or with medication.

1. Engage the patient by showing interest in the voices. Ask: “When did the voices start? Where are they coming from? Can you bring them on or stop them? Do they tell you to do things? What happens when you ignore them?”

2. Normalize the hallucination. List scientifically plausible “reasons for hearing voices,”² including sleep deprivation, isolation, dehydration and/or starvation, extreme stress, strong thoughts or emotions, fever and illness, and drug/alcohol use.

Ask which reasons might apply. Patients often agree with several explanations and begin questioning their delusional interpretations. Your list should include the possibility that the voices are real, but only if the patient initially believes this.

3. Suggest coping strategies, such as:

• humming or singing a song several times
• listening to music
• reading (forwards and backwards)
• talking with others
• exercise
• ignoring the voices
• medication (important to include).

Ask which methods worked previously and have patients build on that list, if possible.

If a patient hears command hallucinations, assess their acuity and decide whether he or she is likely to act on them before starting CBT.

4. Use in-session voices to teach coping strategies. Ask the patient to hum a song with you (“Happy Birthday” works well). If unsuccessful, try reading a paragraph together forwards or backwards. If the voices stop—even for 2 minutes—tell the patient that he or she has begun to control them.³ Have the patient practice these exercises at home and notice if the voices stop for longer periods.

5. Briefly explain the neurology behind the voices. PET scans have shown that auditory hallucinations activate brain areas that regulate hearing and speaking,⁴ suggesting that people talk or think to themselves while hearing voices.

When patients ask why they hear strange voices, explain that many voices are buried inside our memory. When people hear voices, the brain’s speech, hearing, and memory centers interact.⁵

That said, calling auditory hallucinations “voice-thoughts,” rather than “voices,” reduces stigma and reinforces an alternate explanation behind the delusion. As the patient begins to understand that hallucinations are related to dysfunctional thoughts, we can help correct them.

Pharmaceutical companies, through detailers and assistance programs, offer resources for helping our financially strapped patients.

Drug company representatives. Doctors may consider visits from drug reps a waste of time, but we can give the coupons and free drug samples they offer to indigent, disabled, or working-poor patients who often cannot afford the psychotropics they need.

To make meetings with detailers more productive:

• Be clear about your needs, expectations, and how much time you are willing to spend.
  
• Be frank about whether you want to hear about studies. Tell the detailer that you’ll accept information by request only.
  
• State specific dates and times you are available.
  
• Request coupons for patients whose medication samples are likely to be lost or stolen.
  

Patient assistance programs. Pharmaceutical companies’ assistance programs provide deeply discounted drugs to patients in need (Box). The paperwork to qualify takes minutes for clinician and patient to fill out, and many forms are available online or via fax.

Box

Pharmaceutical companies, through detailers and assistance programs, offer resources for helping our financially strapped patients.

Drug company representatives. Doctors may consider visits from drug reps a waste of time, but we can give the coupons and free drug samples they offer to indigent, disabled, or working-poor patients who often cannot afford the psychotropics they need.

To make meetings with detailers more productive:

• Be clear about your needs, expectations, and how much time you are willing to spend.
  
• Be frank about whether you want to hear about studies. Tell the detailer that you’ll accept information by request only.
  
• State specific dates and times you are available.
  
• Request coupons for patients whose medication samples are likely to be lost or stolen.
  

Patient assistance programs. Pharmaceutical companies’ assistance programs provide deeply discounted drugs to patients in need (Box). The paperwork to qualify takes minutes for clinician and patient to fill out, and many forms are available online or via fax.

Box

Pharmaceutical companies, through detailers and assistance programs, offer resources for helping our financially strapped patients.

Drug company representatives. Doctors may consider visits from drug reps a waste of time, but we can give the coupons and free drug samples they offer to indigent, disabled, or working-poor patients who often cannot afford the psychotropics they need.

To make meetings with detailers more productive:

• Be clear about your needs, expectations, and how much time you are willing to spend.
  
• Be frank about whether you want to hear about studies. Tell the detailer that you’ll accept information by request only.
  
• State specific dates and times you are available.
  
• Request coupons for patients whose medication samples are likely to be lost or stolen.
  

Patient assistance programs. Pharmaceutical companies’ assistance programs provide deeply discounted drugs to patients in need (Box). The paperwork to qualify takes minutes for clinician and patient to fill out, and many forms are available online or via fax.

Box