Current Psychiatry

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

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

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

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

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.

CHIEF COMPLAINT: Anxiety and disordered sleep

Mr. Q, a college sophomore, reported symptoms of insomnia, anxiety, and sadness to the university health service. When in bed, he said, he would ruminate about whether he had studied adequately and would ultimately qualify for a graduate program. He exhibited no pervasive sadness, loss of interest or motivation, suicidal ideation, or loss of self-esteem. His medical history revealed no serious illness.

The student health psychiatrist diagnosed Mr. Q as having generalized anxiety disorder. She prescribed trazodone, up to 100 mg/d as needed, for the insomnia. For the next 3 weeks, he took one 25 mg dose each night. After that time, Mr. Q reported that the trazodone alleviated the insomnia and that he felt more rested and could study more effectively. He had stopped taking the medication.

Mr. Q, however, did not tell the health service psychiatrist that he had also experienced an uncomfortable erection that lasted about 4 hours and was not precipitated or accompanied by sexual activity. He finally experienced detumescence after several cold showers. He did not inform her of the episode because he felt embarrassed to discuss “such a thing” with a female physician.

After his anxiety and insomnia resurfaced, Mr. Q was referred to one of the authors.

Why did Mr. Q. develop priapism? How would you counsel him at this point?

Dr. Freed’s and Dr. Muskin’s observations

Priapism refers to a prolonged and painful erection that results from sustained blood flow into the corpora cavernosa. In contrast to a normal erection, both the corpus spongiosum and glans penis remain flaccid. Medical complications and reactions to drugs are well-documented causes.

Table 1

Drugs reported to cause priapism

An erection in priapism may result from sexual stimulation/activity, although this is not typical. Sexually stimulated erections in priapism persist hours after the stimulation ceases.

High-flow priapism is rare, painless, and occurs when well-oxygenated blood stays in the corpora cavernosa. It may result from perineal trauma creating a fistula between an artery and the cavernosa. Because the blood is oxygenated, there is no tissue damage, intervention is not urgent, and the prognosis usually is good.

Low-flow priapism, the more prevalent type, is painful and occurs when venous blood remains in the corpora, resulting in hypoxia and ischemia. Approximately 50% of low-flow priapism cases can result in impotence.¹

Because men often are embarrassed by priapism, they may not seek medical attention or mention a prior episode to their physicians. This neglect can be dangerous: Painful erections that persist for more than 4 hours can lead to impotence if left untreated.

The physician must surmount the patient’s reluctance to discuss the symptom. Inquiring about past priapism episodes as part of a complete patient history is essential. We suggest routinely asking patients taking priapism-causing psychotropics (Table 1) if they’ve had a recent erectile problem. Mentioning that a medication can cause uncomfortable and serious sexual side effects may prompt the patient to discuss such problems.

Above all, be direct. A straightforward inquiry about a sensitive medical condition usually draws an honest answer; the patient then realizes the subject is important and should not be embarrassed about it.

After the patient discloses a priapism episode, ask him:

• Was the erection related to sexual activity or desire?
• Were you using any other medications or illicit drugs when the erection occurred?
• Do you have a systemic blood disorder?
• Did you feel any pain during your erection? If so, how long did it persist?

Men who present during a priapism episode should immediately be sent to the ER for urologic treatment. Patients reporting a recent sustained erection should be referred to a urologist if they need to keep taking the priapism-causing drug. Urologic treatment is not necessary if the patient stops the medication and the priapism resolves.

Men who have had at least one past priapism episode and those taking alpha-adrenergic blockers should be instructed to visit the ER immediately if a painful, persistent erection develops. Patients also should be warned not to induce detumescence (such as by taking cold showers, drinking alcohol, or engaging in sexual activity) if the erection persists for more than 2 hours. Any delay in emergency care could lead to impotence.

HISTORY: A probable side effect

Because Mr. Q had no other past erectile problems, we strongly suspected his priapism was medication-induced. He reported he had neither been drinking nor taking illicit drugs or other medications when the erection occurred.

Mr. Q also was convinced that the trazodone had caused the sustained erection. He said, however, he was never informed that priapism was a potential side effect of that medication.

Would you resume trazodone, switch to another sleep-promoting or antianxiety medication, or consider other therapy?

Dr. Freed’s and Dr. Muskin’s observations

The prevalence of priapism is not known, although yearly estimates range from 1/1,000 to 1/10,000 patients who take trazodone.²

Trazodone, an alpha-adrenergic blocker, is most commonly implicated among psychotropics in causing priapism.² Blockade of alpha-adrenergic receptors in the corpora cavernosa creates a parasympathetic imbalance favoring erection and prevents sympathetic-mediated detumescence. Histaminic, beta-adrenergic, and adrenergic/cholinergic components may also contribute to priapism.

Other medications associated with priapism include antipsychotics, antihypertensives, anticoagulants, some antidepressants, and antiimpotence medications injected into the penis.

Low-flow priapism can also be caused by systemic disorders (Table 2), including malignancies—particularly when a tumor has infiltrated the penis—and carcinoma of the bladder or prostate. Prostatitis has been implicated in some cases.

Table 2

Systemic illnesses and conditions that can cause priapism

Because Mr. Q has had at least one priapism episode, we would avoid prescribing any agent with alpha-adrenergic blocking properties.

Could Mr. Q’s response to trazodone have been dose-related? How would you ensure that the patient understands a medication’s risks?

Dr. Freed’s and Dr. Muskin’s observations

No findings indicate that trazodone-related priapism is dose-related. Several cases of men developing sustained priapism—resulting in permanent injury and impotence—have been reported after initial dosages of 25 and 50 mg/d.^1,4,7 In a study using the FDA Spontaneous Reporting System, Warner et al found that priapism with trazodone was most likely to occur within the first month of treatment and at dosages 150 mg/d.7 Still other reports indicate that new-onset priapism may occur after years of treatment.³

Box 1

Box 2

Despite its association with priapism, trazodone is used frequently in men and is a popular medication for disordered sleep. Nierenberg et al demonstrated improved sleep in 67% of depressed patients with insomnia who received trazodone either for depression or disordered sleep.⁸

When prescribing a priapism-causing agent, make sure the patient understands that erectile effects—though rare—can occur. Consider giving patients an informed consent form explaining the association between psychotropics and priapism and the potential long-term health implications (Box 1). Include the form in the patient’s record for documentation in the event of a malpractice lawsuit (Box 2).

FURTHER TREATMENT: Learning how to cope

Self-hypnosis/relaxation therapy was initiated to address Mr. Q’s anxiety and insomnia. The patient quickly learned the hypnosis techniques and his anxiety/insomnia symptoms began to resolve almost immediately.

Mr. Q’s priapism resolved spontaneously with no apparent erectile dysfunction. He was referred back to the university health service and has been in apparent good health since.

Related resources

• Sleepnet.com. Information on sleep disorders and sleep hygiene. http://www.sleepnet.com/
• National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/

Drug brand names

• Bupropion • Wellbutrin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Labetalol • Trandate
• Levomepromazine • Nozinan
• Mesoridazine • Serentil
• Metoclopramide • Reglan
• Molindone • Lidone
• Perphenazine • Trilafon
• Phenelzine • Nardil
• Prazosin • Minipress
• Promazine • Sparine
• Risperidone • Risperdal
• Sertraline • Zoloft
• Sildenafil citrate • Viagra
• Thioridazine • Mellaril
• Thiothixene • Navane
• Trazodone • Desyrel

Disclosure

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

Dr. Muskin receives research/grant support from Bristol-Myers Squibb Co., is a speaker for and consultant to Bristol-Myers Squibb Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc.; and is a speaker for Cephalon Inc. and Eli Lilly and Co.

Patients who dread the stigma of in-person psychotherapy are substituting traditional “couch trips” with computer sessions.

Computer-based therapy programs, either online or on CD-ROM or DVD, have become popular adjuncts to traditional therapy for patients with mild depression or anxiety. For example, more than 17,000 users visited the MoodGYM site within 6 months, and more than 20% of these users stayed on the site for 16 minutes or more.¹

Computerized psychotherapy has demonstrated numerous benefits in clinical studies and may reduce the time a therapist needs to spend with the patient.

How computer therapy works

Computer-based psychotherapy has its roots in the ELIZA² program developed in 1966 to study natural language communication between man and machine.³ Users simply write a normal sentence, and ELIZA responds appropriately.

The original ELIZA program, which works via text parsing, is limited in its ability to respond. For example, a user who types in “I feel depressed every day” may repeatedly get a response such as “Are you sure?”

Today’s programs are more sophisticated, utilizing specialized heuristic techniques and semantic databases to produce more natural responses to various expressions. Some programs even have audio and video features.

Most computer-based therapy programs employ a cognitive-behavioral treatment model, similar to that used in print workbooks. Several key concepts are presented, such as the relationship between automatic thoughts and feelings; techniques to control these thoughts are highlighted.

Many programs also use common scales to determine depression or anxiety ratings, thus helping the user choose an appropriate module.

Advantages of computer psychotherapy

Computer-based programs offer patients advantages such as:

• Increased comfort. Without the social cues and dynamics that characterize traditional psychotherapy, some patients may disclose feelings online they would feel uncomfortable sharing in person. Online therapy also is immune to the fatigue, illness, boredom, or exploitation that may occur in a relationship with a therapist.
• Flexibility. Users can work the program at home, at their convenience and pace. Responses to exercises also can be stored for future reference.
• Speed of care. Treatment is accessed with minimal delay.
• A greater sense of empowerment. Whereas patients in traditional therapy often feel dependent upon their therapist for direction, computer-based therapy encourages users to take a more active learning role by choosing where to click and how to respond. Patients feel more in control because they are helping themselves.
• Cost-effectiveness. Although price varies, some programs cost about the same as one in-person session. Most programs are sold directly to medical practices.

Disadvantages

Some patients will not benefit from self-help. Those with moderate to severe depression or anxiety may be unable to focus on the material, and inability to navigate the program can increase the patent’s despondency or anxiety. Personality type also may predict lack of response to self-help treatment.⁴

Patients with poor eyesight, deficient reading skills, and limited computer proficiency are not good candidates for online or CD-ROM-based therapy. Also, some computers may not be sufficiently powerful to run some programs, and not all Internet connections are fast enough to post multimedia features.

Clinical effectiveness

In 1990, Selmi et al⁵ compared a six-session, cognitive-behavioral therapy (CBT) course in CD-ROM with six therapist-administered CBT sessions and a control group. An experimenter assisted with computer operation, and both courses followed an identical treatment model and required homework. Patients in both treatment groups demonstrated significant improvement based on Beck Depression Inventory and Automatic Thoughts Questionnaire scores.

Each group comprised only 12 patients, most of whom were young and well-educated. Still, Selmi et al provided initial evidence of computer-based therapy’s effectiveness and these findings have been replicated in subsequent studies. A meta-analysis of 16 studies⁶ found that CD-ROM-based and therapist-administered CBT work equally well in clinically depressed and anxious outpatients. More studies are needed to determine optimal levels of therapist involvement.

More research also is needed to gauge the effectiveness of Internet-based therapy programs (Table). Clarke et al randomized 144 out of 299 patients in a nonprofit health maintenance organization to online therapy with the Overcoming Depression on the Internet (ODIN) program or to treatment as usual. The study demonstrated no effect for ODIN, perhaps because of severity of depression or infrequent access to the site.⁷

Table

Samples of computer-based psychotherapy programs

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Patients who dread the stigma of in-person psychotherapy are substituting traditional “couch trips” with computer sessions.

Computer-based therapy programs, either online or on CD-ROM or DVD, have become popular adjuncts to traditional therapy for patients with mild depression or anxiety. For example, more than 17,000 users visited the MoodGYM site within 6 months, and more than 20% of these users stayed on the site for 16 minutes or more.¹

Computerized psychotherapy has demonstrated numerous benefits in clinical studies and may reduce the time a therapist needs to spend with the patient.

How computer therapy works

Computer-based psychotherapy has its roots in the ELIZA² program developed in 1966 to study natural language communication between man and machine.³ Users simply write a normal sentence, and ELIZA responds appropriately.

The original ELIZA program, which works via text parsing, is limited in its ability to respond. For example, a user who types in “I feel depressed every day” may repeatedly get a response such as “Are you sure?”

Today’s programs are more sophisticated, utilizing specialized heuristic techniques and semantic databases to produce more natural responses to various expressions. Some programs even have audio and video features.

Most computer-based therapy programs employ a cognitive-behavioral treatment model, similar to that used in print workbooks. Several key concepts are presented, such as the relationship between automatic thoughts and feelings; techniques to control these thoughts are highlighted.

Many programs also use common scales to determine depression or anxiety ratings, thus helping the user choose an appropriate module.

Advantages of computer psychotherapy

Computer-based programs offer patients advantages such as:

• Increased comfort. Without the social cues and dynamics that characterize traditional psychotherapy, some patients may disclose feelings online they would feel uncomfortable sharing in person. Online therapy also is immune to the fatigue, illness, boredom, or exploitation that may occur in a relationship with a therapist.
• Flexibility. Users can work the program at home, at their convenience and pace. Responses to exercises also can be stored for future reference.
• Speed of care. Treatment is accessed with minimal delay.
• A greater sense of empowerment. Whereas patients in traditional therapy often feel dependent upon their therapist for direction, computer-based therapy encourages users to take a more active learning role by choosing where to click and how to respond. Patients feel more in control because they are helping themselves.
• Cost-effectiveness. Although price varies, some programs cost about the same as one in-person session. Most programs are sold directly to medical practices.

Disadvantages

Some patients will not benefit from self-help. Those with moderate to severe depression or anxiety may be unable to focus on the material, and inability to navigate the program can increase the patent’s despondency or anxiety. Personality type also may predict lack of response to self-help treatment.⁴

Patients with poor eyesight, deficient reading skills, and limited computer proficiency are not good candidates for online or CD-ROM-based therapy. Also, some computers may not be sufficiently powerful to run some programs, and not all Internet connections are fast enough to post multimedia features.

Clinical effectiveness

In 1990, Selmi et al⁵ compared a six-session, cognitive-behavioral therapy (CBT) course in CD-ROM with six therapist-administered CBT sessions and a control group. An experimenter assisted with computer operation, and both courses followed an identical treatment model and required homework. Patients in both treatment groups demonstrated significant improvement based on Beck Depression Inventory and Automatic Thoughts Questionnaire scores.

Each group comprised only 12 patients, most of whom were young and well-educated. Still, Selmi et al provided initial evidence of computer-based therapy’s effectiveness and these findings have been replicated in subsequent studies. A meta-analysis of 16 studies⁶ found that CD-ROM-based and therapist-administered CBT work equally well in clinically depressed and anxious outpatients. More studies are needed to determine optimal levels of therapist involvement.

More research also is needed to gauge the effectiveness of Internet-based therapy programs (Table). Clarke et al randomized 144 out of 299 patients in a nonprofit health maintenance organization to online therapy with the Overcoming Depression on the Internet (ODIN) program or to treatment as usual. The study demonstrated no effect for ODIN, perhaps because of severity of depression or infrequent access to the site.⁷

Table

Samples of computer-based psychotherapy programs

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Patients who dread the stigma of in-person psychotherapy are substituting traditional “couch trips” with computer sessions.

Computer-based therapy programs, either online or on CD-ROM or DVD, have become popular adjuncts to traditional therapy for patients with mild depression or anxiety. For example, more than 17,000 users visited the MoodGYM site within 6 months, and more than 20% of these users stayed on the site for 16 minutes or more.¹

Computerized psychotherapy has demonstrated numerous benefits in clinical studies and may reduce the time a therapist needs to spend with the patient.

How computer therapy works

Computer-based psychotherapy has its roots in the ELIZA² program developed in 1966 to study natural language communication between man and machine.³ Users simply write a normal sentence, and ELIZA responds appropriately.

The original ELIZA program, which works via text parsing, is limited in its ability to respond. For example, a user who types in “I feel depressed every day” may repeatedly get a response such as “Are you sure?”

Today’s programs are more sophisticated, utilizing specialized heuristic techniques and semantic databases to produce more natural responses to various expressions. Some programs even have audio and video features.

Most computer-based therapy programs employ a cognitive-behavioral treatment model, similar to that used in print workbooks. Several key concepts are presented, such as the relationship between automatic thoughts and feelings; techniques to control these thoughts are highlighted.

Many programs also use common scales to determine depression or anxiety ratings, thus helping the user choose an appropriate module.

Advantages of computer psychotherapy

Computer-based programs offer patients advantages such as:

• Increased comfort. Without the social cues and dynamics that characterize traditional psychotherapy, some patients may disclose feelings online they would feel uncomfortable sharing in person. Online therapy also is immune to the fatigue, illness, boredom, or exploitation that may occur in a relationship with a therapist.
• Flexibility. Users can work the program at home, at their convenience and pace. Responses to exercises also can be stored for future reference.
• Speed of care. Treatment is accessed with minimal delay.
• A greater sense of empowerment. Whereas patients in traditional therapy often feel dependent upon their therapist for direction, computer-based therapy encourages users to take a more active learning role by choosing where to click and how to respond. Patients feel more in control because they are helping themselves.
• Cost-effectiveness. Although price varies, some programs cost about the same as one in-person session. Most programs are sold directly to medical practices.

Disadvantages

Some patients will not benefit from self-help. Those with moderate to severe depression or anxiety may be unable to focus on the material, and inability to navigate the program can increase the patent’s despondency or anxiety. Personality type also may predict lack of response to self-help treatment.⁴

Patients with poor eyesight, deficient reading skills, and limited computer proficiency are not good candidates for online or CD-ROM-based therapy. Also, some computers may not be sufficiently powerful to run some programs, and not all Internet connections are fast enough to post multimedia features.

Clinical effectiveness

In 1990, Selmi et al⁵ compared a six-session, cognitive-behavioral therapy (CBT) course in CD-ROM with six therapist-administered CBT sessions and a control group. An experimenter assisted with computer operation, and both courses followed an identical treatment model and required homework. Patients in both treatment groups demonstrated significant improvement based on Beck Depression Inventory and Automatic Thoughts Questionnaire scores.

Each group comprised only 12 patients, most of whom were young and well-educated. Still, Selmi et al provided initial evidence of computer-based therapy’s effectiveness and these findings have been replicated in subsequent studies. A meta-analysis of 16 studies⁶ found that CD-ROM-based and therapist-administered CBT work equally well in clinically depressed and anxious outpatients. More studies are needed to determine optimal levels of therapist involvement.

More research also is needed to gauge the effectiveness of Internet-based therapy programs (Table). Clarke et al randomized 144 out of 299 patients in a nonprofit health maintenance organization to online therapy with the Overcoming Depression on the Internet (ODIN) program or to treatment as usual. The study demonstrated no effect for ODIN, perhaps because of severity of depression or infrequent access to the site.⁷

Table

Samples of computer-based psychotherapy programs

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

To me, the main difference between MDs and PhDs* is that MDs—at some point—must stop gathering data and make decisions.

I once heard Dr. Albert (Mickey) Stunkard say that when he was a physician fellow at Stanford University’s Center for Advanced Studies in the Behavioral Sciences he was at first energized—and a little intimidated—by the scintillating conversations taking place around him. Eventually, though, all the discourse reminded him of those long, philosophical discussions he and his classmates had had in their college dorms (“Well, on one hand you have communism, and on the other hand you have fascism… ”).

Physicians do not have the luxury of endless debate. At some point, we need to do something or else let our patients die of old age while waiting. One issue about which I have had to make decisions over the years—and which has troubled me the most—is whether to treat pregnant patients with psychotropics. Generally, I try to avoid using drugs in these cases, but sometimes I decide that the mother’s need for drug therapy outweighs the potential risks to her offspring.

Dr. Lori Altshuler and colleagues’ article in this issue is the best summary I have seen of what is known about the risks of using psychotropics in pregnant bipolar women. Each time I treat a woman with bipolar disorder, I will remember this discussion and the algorithm these authors suggest for making therapeutic decisions.

This excellent article may not be the final word on the subject. It can, however, help us with an important clinical decision we often have to make—and that is what Current Psychiatry is all about.

To me, the main difference between MDs and PhDs* is that MDs—at some point—must stop gathering data and make decisions.

I once heard Dr. Albert (Mickey) Stunkard say that when he was a physician fellow at Stanford University’s Center for Advanced Studies in the Behavioral Sciences he was at first energized—and a little intimidated—by the scintillating conversations taking place around him. Eventually, though, all the discourse reminded him of those long, philosophical discussions he and his classmates had had in their college dorms (“Well, on one hand you have communism, and on the other hand you have fascism… ”).

Physicians do not have the luxury of endless debate. At some point, we need to do something or else let our patients die of old age while waiting. One issue about which I have had to make decisions over the years—and which has troubled me the most—is whether to treat pregnant patients with psychotropics. Generally, I try to avoid using drugs in these cases, but sometimes I decide that the mother’s need for drug therapy outweighs the potential risks to her offspring.

Dr. Lori Altshuler and colleagues’ article in this issue is the best summary I have seen of what is known about the risks of using psychotropics in pregnant bipolar women. Each time I treat a woman with bipolar disorder, I will remember this discussion and the algorithm these authors suggest for making therapeutic decisions.

This excellent article may not be the final word on the subject. It can, however, help us with an important clinical decision we often have to make—and that is what Current Psychiatry is all about.

To me, the main difference between MDs and PhDs* is that MDs—at some point—must stop gathering data and make decisions.

I once heard Dr. Albert (Mickey) Stunkard say that when he was a physician fellow at Stanford University’s Center for Advanced Studies in the Behavioral Sciences he was at first energized—and a little intimidated—by the scintillating conversations taking place around him. Eventually, though, all the discourse reminded him of those long, philosophical discussions he and his classmates had had in their college dorms (“Well, on one hand you have communism, and on the other hand you have fascism… ”).

Physicians do not have the luxury of endless debate. At some point, we need to do something or else let our patients die of old age while waiting. One issue about which I have had to make decisions over the years—and which has troubled me the most—is whether to treat pregnant patients with psychotropics. Generally, I try to avoid using drugs in these cases, but sometimes I decide that the mother’s need for drug therapy outweighs the potential risks to her offspring.

Dr. Lori Altshuler and colleagues’ article in this issue is the best summary I have seen of what is known about the risks of using psychotropics in pregnant bipolar women. Each time I treat a woman with bipolar disorder, I will remember this discussion and the algorithm these authors suggest for making therapeutic decisions.

This excellent article may not be the final word on the subject. It can, however, help us with an important clinical decision we often have to make—and that is what Current Psychiatry is all about.

Using magnets to improve health is sometimes hawked in dubious classified ads and “infomercials.” However, a legitimate use of magnetism—repetitive transcranial magnetic stimulation (rTMS)—is showing promise in treating severe depression (Box) ^1-4 and other psychiatric disorders.

Patients or their families are likely to ask psychiatrists about rTMS as more becomes known about this investigational technology. Drawing from our experience and the evidence, we offer an update on whether rTMS may be an alternative for treating depression and address issues that must be resolved before it could be used in clinical practice.

WHAT IS RTMS?

rTMS consists of a series of magnetic pulses produced by a stimulator, which can be adjusted for:

• coil type and placement
• stimulation site, intensity, frequency, and number
• amount of time between stimulations
• treatment duration.

Box

Coil type and placement. Initial studies involved stimulation—typically low-frequency—over the vertex, but most subsequent rTMS trials in depression have stimulated the left dorsolateral prefrontal cortex. Neuroimaging studies have shown prefrontal functioning abnormalities in depressed subjects, and it is hypothesized that stimulating this area (plus possible distal effects) may produce an antidepressant effect.⁵

Various configurations have been used, but circular and figure-eight-shaped coils are most common. These flat coils are made of tightly wound ferromagnetic material such as copper, enclosed in a heavy plastic cover. With the figure-eight coil, the intersection of the two loops produces the strongest magnetic field.

Stimulation site. Stimulation intensity depends on the individual’s motor threshold, and the site can be determined visually or electrophysiologically.

• With the visual method, the motor threshold over the left primary motor cortex site for the first dorsal interosseous muscle (FDI) or the abductor pollius brevis (APB) is determined by iteration. This involves placing the coil at a progression of sites and increasing stimulation intensity until reliable (in 5 of 10 stimulations) contractions are seen in the right FDI or APB.
• Similarly, the electrophysiologic method uses 5 of 10 motorevoked potentials of 50 microvolts to locate the site.

The only small trial that compared visual and electrophysiologic site determination showed similar results with both methods.⁶ The most common stimulation site is the left dorsolateral prefrontal cortex, 5 cm anterior and parasagittal to the FDI or APB motor cortex. Alternately, frameless stereotactic systems or the international 10-20 proportional system used in EEG labs have been recommended to target sites more accurately.

Stimulus intensity. Each individual’s motor threshold determines stimulus intensity. Using functional MRI studies, researchers from the Medical University of South Carolina concluded that higher stimulation intensity relative to the motor threshold may have a more robust effect, as the magnetic field declines with distance from the coil.⁷ However, intensities >120% of the motor threshold are generally avoided because of possible increased seizure risk.⁹

Frequency of stimulation. Most researchers apply frequencies of 1 to 20 Hz over the left dorsolateral prefrontal cortex, but also use lower frequencies (<1 Hz) over the right dorsolateral prefrontal cortex. Using higher frequencies in major depression is attractive in theory because of:

• the reported association of decreased regional cerebral blood flow with hypometabolism in the left dorsolateral prefrontal cortex
• higher-frequency stimulation’s ability to produce temporary excitation and neuronal depolarization.

Number of stimulations. The number of stimulations is determined by frequency (Hz) and stimulation train duration (for example, 10 Hz for 5 seconds equals 50 stimulations). A typical treatment session incorporates 10 to 30 stimulation trains several seconds apart (the inter-train interval). Thus, a typical session delivers 1,000 to 1,200 stimulations. In studies of unmedicated depressed patients, the total number of stimulations has varied from 8,000 to 32,000 per treatment course.

Duration between two stimulation trains. Chen et al have demonstrated that shorter (<1 second) inter-train intervals increase seizure risk with higher frequencies (such as 20 Hz) and intensities (>100% of motor threshold) of stimulation.⁹ Based on their studies with healthy volunteers, they recommended several “safe” ranges (such as 5 seconds at 110% of motor threshold). Most trials use 30- to 60-second inter-train intervals.

Most treatments continue 2 to 4 weeks, Monday through Friday, although more frequent treatments are being studied.

EFFICACY FOR DEPRESSION

Most studies of rTMS in depression have compared real rTMS to a sham control or electroconvulsive therapy (ECT).

In earlier studies, the sham procedure typically involved tilting the coil away from the skull. This method has been questioned, however, because of evidence of neuronal depolarization.¹⁰

More recent sham coils mimic the real coils’ sound and sensation, without magnetic stimulation.

Despite these methodologic problems and some mixed results, depressed patients receiving rTMS show more favorable results than those receiving sham rTMS.^11,12 Several meta-analyses have attempted to quantify rTMS’ efficacy for depression:

• Holtzheimer et al concluded that rTMS was statistically superior to sham rTMS, but the clinical significance of these findings was modest in a population of mostly outpatients with less-severe depression.¹³
• Burt et al found a statistically strong antidepressant effect, but its magnitude varied and few of the studies yielded a substantial clinical response or remission. The team also noted that rTMS’ long-term efficacy or adverse effects are unknown.¹⁴
• Kozel et al concluded that left prefrontal rTMS rendered a significant antidepressant effect with measurable clinical improvement.¹⁵
• Gershon et al¹⁶ supported an antidepressant effect for rTMS when compared with sham rTMS or ECT.

Ongoing rTMS research includes subjects with many types of mild to severe psychiatric illnesses, including major depression, obsessive-compulsive disorder, and psychosis. Typically, patients referred for experimental approaches have not responded to or tolerated available treatments. Exclusion criteria used by most rTMS studies are listed in the Table.

Table

Medical conditions that preclude use of rTMS

rTMS vs. ECT. Four randomized, controlled trials have compared rTMS with ECT for treating severely ill, often medication-resistant patients.^17-20 Although their methodologies differed, all four studies concluded that rTMS and ECT offer similar efficacy, except that rTMS may be less effective for treating psychotic depression.

One study found ECT more effective than rTMS for psychotic depression, although the patients who received ECT were also treated with antipsychotics and/or antidepressants.¹⁷ Our study,¹⁹ which did not use these agents, has not corroborated this observation. Preliminary data also indicate comparable relapse rates following acute ECT and rTMS when subjects are followed on maintenance medication.²¹

ADVERSE EFFECTS

The potential adverse effects of new treatments must always be considered. Thus far, rTMS appears to produce minimal, relatively benign complications, including:

• mild discomfort at the stimulation site
• localized muscle twitching during stimulation
• mild post-treatment headaches—believed caused by muscle contractions—which usually respond to aspirin or acetaminophen
• treatment stimulation-related seizures (rarely).⁸

The rTMS device makes a loud clicking noise, and subjects wear protective ear plugs during treatment.

Patient experience. The first rTMS session—during which the patient’s motor threshold is determined—can last up to 45 minutes. Subsequent sessions are usually 15 to 20 minutes. Patients are typically apprehensive before the first session but become more relaxed with experience and tolerate the treatments easily.

During the procedure, many patients describe a tapping sensation on the forehead, and some experience slight muscle twitching around the eye or corner of the mouth. As the coil warms, the skin it touches sometimes flushes pink, although this does not seem to bother our patients. They can return to their daily routines immediately after a session.

rTMS for major depression. In our experience, rTMS may help patients with major depression. For example, one patient diagnosed with a major depressive episode with psychotic features was referred to our study comparing rTMS with ECT.¹⁹ Her depression had lasted several months, with partial response to ECT treatments. She signed informed consent and was randomly assigned to receive rTMS treatment.

At study admission, the patient’s Hamilton Depression Rating Scale (HDRS) score was 48, indicating moderate to severe depression. Following 10 rTMS sessions, her HDRS score had dropped to 2, with remission of symptoms. No follow-up results were documented.

Cognitive effects. Whereas mood disorders are associated with medication-independent neuropsychological deficits, most studies have found no adverse cognitive effects with rTMS.²² Indeed, some of our rTMS patients have improved in certain cognitive tests, although this may be explained by test-retest effects or better attention and concentration associated with mood improvement.

Figure Potential roles for rTMS in treating major depression

Solid lines represent current standards of practice. Dotted lines represent hypothetical roles for rTMS.

Source: Adapted and reprinted with permission from Dowd et al. Is repetitive transcranial magnetic stimulation an alternative to ECTfor the treatment of depression? Contemp Psychiatry 2002;1:1-10.

POTENTIAL ROLE FOR rTMS

Today’s standard treatment of major depressive episodes begins with an antidepressant (plus an antipsychotic, if necessary) and proceeds to augmentation strategies if response is insufficient. rTMS may one day become an augmentation or monotherapy option for patients who do not respond sufficiently to standard treatments (Figure).

ECT treatment may be initiated if a patient has had a prior good response to ECT, is intolerant to medication, or prefers ECT. In that case, rTMS may be used as an alternate initial treatment or with ECT. Thus, rTMS may be used:

• to augment antidepressants
• as an alternative to antidepressants or ECT
• or sequentially with ECT.

Before that can happen, however, optimal treatment parameters need to be clarified by larger, well-designed, controlled studies comparing rTMS to a valid sham treatment, antidepressants, and ECT.

Related resources

• International Society for Transcranial Stimulation. www.ists.unibe.ch/
• Repetitive Transcranial Magnetic Stimulation Research Clinic at Yale-New Haven Psychiatric Hospital.

Disclosure

The authors report that they have no proprietary interest in the technology discussed in this article.

Using magnets to improve health is sometimes hawked in dubious classified ads and “infomercials.” However, a legitimate use of magnetism—repetitive transcranial magnetic stimulation (rTMS)—is showing promise in treating severe depression (Box) ^1-4 and other psychiatric disorders.

Patients or their families are likely to ask psychiatrists about rTMS as more becomes known about this investigational technology. Drawing from our experience and the evidence, we offer an update on whether rTMS may be an alternative for treating depression and address issues that must be resolved before it could be used in clinical practice.

WHAT IS RTMS?

rTMS consists of a series of magnetic pulses produced by a stimulator, which can be adjusted for:

• coil type and placement
• stimulation site, intensity, frequency, and number
• amount of time between stimulations
• treatment duration.

Box

Coil type and placement. Initial studies involved stimulation—typically low-frequency—over the vertex, but most subsequent rTMS trials in depression have stimulated the left dorsolateral prefrontal cortex. Neuroimaging studies have shown prefrontal functioning abnormalities in depressed subjects, and it is hypothesized that stimulating this area (plus possible distal effects) may produce an antidepressant effect.⁵

Various configurations have been used, but circular and figure-eight-shaped coils are most common. These flat coils are made of tightly wound ferromagnetic material such as copper, enclosed in a heavy plastic cover. With the figure-eight coil, the intersection of the two loops produces the strongest magnetic field.

Stimulation site. Stimulation intensity depends on the individual’s motor threshold, and the site can be determined visually or electrophysiologically.

• With the visual method, the motor threshold over the left primary motor cortex site for the first dorsal interosseous muscle (FDI) or the abductor pollius brevis (APB) is determined by iteration. This involves placing the coil at a progression of sites and increasing stimulation intensity until reliable (in 5 of 10 stimulations) contractions are seen in the right FDI or APB.
• Similarly, the electrophysiologic method uses 5 of 10 motorevoked potentials of 50 microvolts to locate the site.

The only small trial that compared visual and electrophysiologic site determination showed similar results with both methods.⁶ The most common stimulation site is the left dorsolateral prefrontal cortex, 5 cm anterior and parasagittal to the FDI or APB motor cortex. Alternately, frameless stereotactic systems or the international 10-20 proportional system used in EEG labs have been recommended to target sites more accurately.

Stimulus intensity. Each individual’s motor threshold determines stimulus intensity. Using functional MRI studies, researchers from the Medical University of South Carolina concluded that higher stimulation intensity relative to the motor threshold may have a more robust effect, as the magnetic field declines with distance from the coil.⁷ However, intensities >120% of the motor threshold are generally avoided because of possible increased seizure risk.⁹

Frequency of stimulation. Most researchers apply frequencies of 1 to 20 Hz over the left dorsolateral prefrontal cortex, but also use lower frequencies (<1 Hz) over the right dorsolateral prefrontal cortex. Using higher frequencies in major depression is attractive in theory because of:

• the reported association of decreased regional cerebral blood flow with hypometabolism in the left dorsolateral prefrontal cortex
• higher-frequency stimulation’s ability to produce temporary excitation and neuronal depolarization.

Number of stimulations. The number of stimulations is determined by frequency (Hz) and stimulation train duration (for example, 10 Hz for 5 seconds equals 50 stimulations). A typical treatment session incorporates 10 to 30 stimulation trains several seconds apart (the inter-train interval). Thus, a typical session delivers 1,000 to 1,200 stimulations. In studies of unmedicated depressed patients, the total number of stimulations has varied from 8,000 to 32,000 per treatment course.

Duration between two stimulation trains. Chen et al have demonstrated that shorter (<1 second) inter-train intervals increase seizure risk with higher frequencies (such as 20 Hz) and intensities (>100% of motor threshold) of stimulation.⁹ Based on their studies with healthy volunteers, they recommended several “safe” ranges (such as 5 seconds at 110% of motor threshold). Most trials use 30- to 60-second inter-train intervals.

Most treatments continue 2 to 4 weeks, Monday through Friday, although more frequent treatments are being studied.

EFFICACY FOR DEPRESSION

Most studies of rTMS in depression have compared real rTMS to a sham control or electroconvulsive therapy (ECT).

In earlier studies, the sham procedure typically involved tilting the coil away from the skull. This method has been questioned, however, because of evidence of neuronal depolarization.¹⁰

More recent sham coils mimic the real coils’ sound and sensation, without magnetic stimulation.

Despite these methodologic problems and some mixed results, depressed patients receiving rTMS show more favorable results than those receiving sham rTMS.^11,12 Several meta-analyses have attempted to quantify rTMS’ efficacy for depression:

• Holtzheimer et al concluded that rTMS was statistically superior to sham rTMS, but the clinical significance of these findings was modest in a population of mostly outpatients with less-severe depression.¹³
• Burt et al found a statistically strong antidepressant effect, but its magnitude varied and few of the studies yielded a substantial clinical response or remission. The team also noted that rTMS’ long-term efficacy or adverse effects are unknown.¹⁴
• Kozel et al concluded that left prefrontal rTMS rendered a significant antidepressant effect with measurable clinical improvement.¹⁵
• Gershon et al¹⁶ supported an antidepressant effect for rTMS when compared with sham rTMS or ECT.

Ongoing rTMS research includes subjects with many types of mild to severe psychiatric illnesses, including major depression, obsessive-compulsive disorder, and psychosis. Typically, patients referred for experimental approaches have not responded to or tolerated available treatments. Exclusion criteria used by most rTMS studies are listed in the Table.

Table

Medical conditions that preclude use of rTMS

rTMS vs. ECT. Four randomized, controlled trials have compared rTMS with ECT for treating severely ill, often medication-resistant patients.^17-20 Although their methodologies differed, all four studies concluded that rTMS and ECT offer similar efficacy, except that rTMS may be less effective for treating psychotic depression.

One study found ECT more effective than rTMS for psychotic depression, although the patients who received ECT were also treated with antipsychotics and/or antidepressants.¹⁷ Our study,¹⁹ which did not use these agents, has not corroborated this observation. Preliminary data also indicate comparable relapse rates following acute ECT and rTMS when subjects are followed on maintenance medication.²¹

ADVERSE EFFECTS

The potential adverse effects of new treatments must always be considered. Thus far, rTMS appears to produce minimal, relatively benign complications, including:

• mild discomfort at the stimulation site
• localized muscle twitching during stimulation
• mild post-treatment headaches—believed caused by muscle contractions—which usually respond to aspirin or acetaminophen
• treatment stimulation-related seizures (rarely).⁸

The rTMS device makes a loud clicking noise, and subjects wear protective ear plugs during treatment.

Patient experience. The first rTMS session—during which the patient’s motor threshold is determined—can last up to 45 minutes. Subsequent sessions are usually 15 to 20 minutes. Patients are typically apprehensive before the first session but become more relaxed with experience and tolerate the treatments easily.

During the procedure, many patients describe a tapping sensation on the forehead, and some experience slight muscle twitching around the eye or corner of the mouth. As the coil warms, the skin it touches sometimes flushes pink, although this does not seem to bother our patients. They can return to their daily routines immediately after a session.

rTMS for major depression. In our experience, rTMS may help patients with major depression. For example, one patient diagnosed with a major depressive episode with psychotic features was referred to our study comparing rTMS with ECT.¹⁹ Her depression had lasted several months, with partial response to ECT treatments. She signed informed consent and was randomly assigned to receive rTMS treatment.

At study admission, the patient’s Hamilton Depression Rating Scale (HDRS) score was 48, indicating moderate to severe depression. Following 10 rTMS sessions, her HDRS score had dropped to 2, with remission of symptoms. No follow-up results were documented.

Cognitive effects. Whereas mood disorders are associated with medication-independent neuropsychological deficits, most studies have found no adverse cognitive effects with rTMS.²² Indeed, some of our rTMS patients have improved in certain cognitive tests, although this may be explained by test-retest effects or better attention and concentration associated with mood improvement.

Figure Potential roles for rTMS in treating major depression

Solid lines represent current standards of practice. Dotted lines represent hypothetical roles for rTMS.

Source: Adapted and reprinted with permission from Dowd et al. Is repetitive transcranial magnetic stimulation an alternative to ECTfor the treatment of depression? Contemp Psychiatry 2002;1:1-10.

POTENTIAL ROLE FOR rTMS

Today’s standard treatment of major depressive episodes begins with an antidepressant (plus an antipsychotic, if necessary) and proceeds to augmentation strategies if response is insufficient. rTMS may one day become an augmentation or monotherapy option for patients who do not respond sufficiently to standard treatments (Figure).

ECT treatment may be initiated if a patient has had a prior good response to ECT, is intolerant to medication, or prefers ECT. In that case, rTMS may be used as an alternate initial treatment or with ECT. Thus, rTMS may be used:

• to augment antidepressants
• as an alternative to antidepressants or ECT
• or sequentially with ECT.

Before that can happen, however, optimal treatment parameters need to be clarified by larger, well-designed, controlled studies comparing rTMS to a valid sham treatment, antidepressants, and ECT.

Related resources

• International Society for Transcranial Stimulation. www.ists.unibe.ch/
• Repetitive Transcranial Magnetic Stimulation Research Clinic at Yale-New Haven Psychiatric Hospital.

Disclosure

The authors report that they have no proprietary interest in the technology discussed in this article.

Using magnets to improve health is sometimes hawked in dubious classified ads and “infomercials.” However, a legitimate use of magnetism—repetitive transcranial magnetic stimulation (rTMS)—is showing promise in treating severe depression (Box) ^1-4 and other psychiatric disorders.

Patients or their families are likely to ask psychiatrists about rTMS as more becomes known about this investigational technology. Drawing from our experience and the evidence, we offer an update on whether rTMS may be an alternative for treating depression and address issues that must be resolved before it could be used in clinical practice.

WHAT IS RTMS?

rTMS consists of a series of magnetic pulses produced by a stimulator, which can be adjusted for:

• coil type and placement
• stimulation site, intensity, frequency, and number
• amount of time between stimulations
• treatment duration.

Box

Coil type and placement. Initial studies involved stimulation—typically low-frequency—over the vertex, but most subsequent rTMS trials in depression have stimulated the left dorsolateral prefrontal cortex. Neuroimaging studies have shown prefrontal functioning abnormalities in depressed subjects, and it is hypothesized that stimulating this area (plus possible distal effects) may produce an antidepressant effect.⁵

Various configurations have been used, but circular and figure-eight-shaped coils are most common. These flat coils are made of tightly wound ferromagnetic material such as copper, enclosed in a heavy plastic cover. With the figure-eight coil, the intersection of the two loops produces the strongest magnetic field.

Stimulation site. Stimulation intensity depends on the individual’s motor threshold, and the site can be determined visually or electrophysiologically.

• With the visual method, the motor threshold over the left primary motor cortex site for the first dorsal interosseous muscle (FDI) or the abductor pollius brevis (APB) is determined by iteration. This involves placing the coil at a progression of sites and increasing stimulation intensity until reliable (in 5 of 10 stimulations) contractions are seen in the right FDI or APB.
• Similarly, the electrophysiologic method uses 5 of 10 motorevoked potentials of 50 microvolts to locate the site.

The only small trial that compared visual and electrophysiologic site determination showed similar results with both methods.⁶ The most common stimulation site is the left dorsolateral prefrontal cortex, 5 cm anterior and parasagittal to the FDI or APB motor cortex. Alternately, frameless stereotactic systems or the international 10-20 proportional system used in EEG labs have been recommended to target sites more accurately.

Stimulus intensity. Each individual’s motor threshold determines stimulus intensity. Using functional MRI studies, researchers from the Medical University of South Carolina concluded that higher stimulation intensity relative to the motor threshold may have a more robust effect, as the magnetic field declines with distance from the coil.⁷ However, intensities >120% of the motor threshold are generally avoided because of possible increased seizure risk.⁹

Frequency of stimulation. Most researchers apply frequencies of 1 to 20 Hz over the left dorsolateral prefrontal cortex, but also use lower frequencies (<1 Hz) over the right dorsolateral prefrontal cortex. Using higher frequencies in major depression is attractive in theory because of:

• the reported association of decreased regional cerebral blood flow with hypometabolism in the left dorsolateral prefrontal cortex
• higher-frequency stimulation’s ability to produce temporary excitation and neuronal depolarization.

Number of stimulations. The number of stimulations is determined by frequency (Hz) and stimulation train duration (for example, 10 Hz for 5 seconds equals 50 stimulations). A typical treatment session incorporates 10 to 30 stimulation trains several seconds apart (the inter-train interval). Thus, a typical session delivers 1,000 to 1,200 stimulations. In studies of unmedicated depressed patients, the total number of stimulations has varied from 8,000 to 32,000 per treatment course.

Duration between two stimulation trains. Chen et al have demonstrated that shorter (<1 second) inter-train intervals increase seizure risk with higher frequencies (such as 20 Hz) and intensities (>100% of motor threshold) of stimulation.⁹ Based on their studies with healthy volunteers, they recommended several “safe” ranges (such as 5 seconds at 110% of motor threshold). Most trials use 30- to 60-second inter-train intervals.

Most treatments continue 2 to 4 weeks, Monday through Friday, although more frequent treatments are being studied.

EFFICACY FOR DEPRESSION

Most studies of rTMS in depression have compared real rTMS to a sham control or electroconvulsive therapy (ECT).

In earlier studies, the sham procedure typically involved tilting the coil away from the skull. This method has been questioned, however, because of evidence of neuronal depolarization.¹⁰

More recent sham coils mimic the real coils’ sound and sensation, without magnetic stimulation.

Despite these methodologic problems and some mixed results, depressed patients receiving rTMS show more favorable results than those receiving sham rTMS.^11,12 Several meta-analyses have attempted to quantify rTMS’ efficacy for depression:

• Holtzheimer et al concluded that rTMS was statistically superior to sham rTMS, but the clinical significance of these findings was modest in a population of mostly outpatients with less-severe depression.¹³
• Burt et al found a statistically strong antidepressant effect, but its magnitude varied and few of the studies yielded a substantial clinical response or remission. The team also noted that rTMS’ long-term efficacy or adverse effects are unknown.¹⁴
• Kozel et al concluded that left prefrontal rTMS rendered a significant antidepressant effect with measurable clinical improvement.¹⁵
• Gershon et al¹⁶ supported an antidepressant effect for rTMS when compared with sham rTMS or ECT.

Ongoing rTMS research includes subjects with many types of mild to severe psychiatric illnesses, including major depression, obsessive-compulsive disorder, and psychosis. Typically, patients referred for experimental approaches have not responded to or tolerated available treatments. Exclusion criteria used by most rTMS studies are listed in the Table.

Table

Medical conditions that preclude use of rTMS

rTMS vs. ECT. Four randomized, controlled trials have compared rTMS with ECT for treating severely ill, often medication-resistant patients.^17-20 Although their methodologies differed, all four studies concluded that rTMS and ECT offer similar efficacy, except that rTMS may be less effective for treating psychotic depression.

One study found ECT more effective than rTMS for psychotic depression, although the patients who received ECT were also treated with antipsychotics and/or antidepressants.¹⁷ Our study,¹⁹ which did not use these agents, has not corroborated this observation. Preliminary data also indicate comparable relapse rates following acute ECT and rTMS when subjects are followed on maintenance medication.²¹

ADVERSE EFFECTS

The potential adverse effects of new treatments must always be considered. Thus far, rTMS appears to produce minimal, relatively benign complications, including:

• mild discomfort at the stimulation site
• localized muscle twitching during stimulation
• mild post-treatment headaches—believed caused by muscle contractions—which usually respond to aspirin or acetaminophen
• treatment stimulation-related seizures (rarely).⁸

The rTMS device makes a loud clicking noise, and subjects wear protective ear plugs during treatment.

Patient experience. The first rTMS session—during which the patient’s motor threshold is determined—can last up to 45 minutes. Subsequent sessions are usually 15 to 20 minutes. Patients are typically apprehensive before the first session but become more relaxed with experience and tolerate the treatments easily.

During the procedure, many patients describe a tapping sensation on the forehead, and some experience slight muscle twitching around the eye or corner of the mouth. As the coil warms, the skin it touches sometimes flushes pink, although this does not seem to bother our patients. They can return to their daily routines immediately after a session.

rTMS for major depression. In our experience, rTMS may help patients with major depression. For example, one patient diagnosed with a major depressive episode with psychotic features was referred to our study comparing rTMS with ECT.¹⁹ Her depression had lasted several months, with partial response to ECT treatments. She signed informed consent and was randomly assigned to receive rTMS treatment.

At study admission, the patient’s Hamilton Depression Rating Scale (HDRS) score was 48, indicating moderate to severe depression. Following 10 rTMS sessions, her HDRS score had dropped to 2, with remission of symptoms. No follow-up results were documented.

Cognitive effects. Whereas mood disorders are associated with medication-independent neuropsychological deficits, most studies have found no adverse cognitive effects with rTMS.²² Indeed, some of our rTMS patients have improved in certain cognitive tests, although this may be explained by test-retest effects or better attention and concentration associated with mood improvement.

Figure Potential roles for rTMS in treating major depression

Solid lines represent current standards of practice. Dotted lines represent hypothetical roles for rTMS.

Source: Adapted and reprinted with permission from Dowd et al. Is repetitive transcranial magnetic stimulation an alternative to ECTfor the treatment of depression? Contemp Psychiatry 2002;1:1-10.

POTENTIAL ROLE FOR rTMS

Today’s standard treatment of major depressive episodes begins with an antidepressant (plus an antipsychotic, if necessary) and proceeds to augmentation strategies if response is insufficient. rTMS may one day become an augmentation or monotherapy option for patients who do not respond sufficiently to standard treatments (Figure).

ECT treatment may be initiated if a patient has had a prior good response to ECT, is intolerant to medication, or prefers ECT. In that case, rTMS may be used as an alternate initial treatment or with ECT. Thus, rTMS may be used:

• to augment antidepressants
• as an alternative to antidepressants or ECT
• or sequentially with ECT.

Before that can happen, however, optimal treatment parameters need to be clarified by larger, well-designed, controlled studies comparing rTMS to a valid sham treatment, antidepressants, and ECT.

Related resources

• International Society for Transcranial Stimulation. www.ists.unibe.ch/
• Repetitive Transcranial Magnetic Stimulation Research Clinic at Yale-New Haven Psychiatric Hospital.

Disclosure

The authors report that they have no proprietary interest in the technology discussed in this article.

Psyber Psychiatry, February. A few voice command programs also are available for Pocket PC devices ARTrecognition, VoiceLookup, PDsay, and VoiceContact allow you to use voice commands to lookup information and launch tasks.

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure:

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Psyber Psychiatry, February. A few voice command programs also are available for Pocket PC devices ARTrecognition, VoiceLookup, PDsay, and VoiceContact allow you to use voice commands to lookup information and launch tasks.

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure:

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Psyber Psychiatry, February. A few voice command programs also are available for Pocket PC devices ARTrecognition, VoiceLookup, PDsay, and VoiceContact allow you to use voice commands to lookup information and launch tasks.

If you have any questions about these products or comments about Psyber Psychiatry, click here to contact Dr. Luo or send an e-mail to [email protected].

Disclosure:

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Long-acting intramuscular (IM) antipsychotics are necessary for patients who do not respond to—or comply with—oral medication regimens. We can make these injections less painful, provided that agitation does not complicate treatment.

In 25 years of practice, I’ve discovered the following ways to diminish the pain of injection:

• Inject into the deltoid’s posterior aspect. Nociceptive pain fibers may be less dense in the posterior versus the anterior deltoid. I try to inject latitudinally about 1 cm behind the deltoid midline and longitudinally about 5 cm below the acromioclavicular joint.
• Inject into the lateral gluteusto avoid stimulating the sciatic nerve that runs down the medial gluteus.
• Have the patient fold his or her arm across the lap.Muscles that are relaxed before injection are less likely to hurt afterward. The arm’s flexed position will help relax the deltoid.
• Massage the muscle area overlying the injection sitefor about 10 seconds before injecting. This further relaxes the muscle.
• Inject slowly—about 30 seconds per cc. A faster injection can increase pain.
• Inject air into the vial before withdrawing. Commonly used injectable psychiatric drugs are based in sesame oil. Withdrawing these viscous medications through the perforation site can be difficult if the vial is partially evacuated and the remaining fluid is under negative atmospheric pressure.

Some clinicians use the “Z technique” to prevent backflow when injecting IM antipsychotics. With this method, skin and subcutaneous tissue are retracted to avoid creating a straight-line needle tract that would allow the ready backflow of injected material.

I feel this method is unnecessary for decanoate preparations; they are viscous enough to prevent significant backflow provided the injection is slowly administered.

To IM or not to IM

Where possible, administering medications subcutaneously instead of intramuscularly can also reduce pain.

Contrary to popular belief, fluphenazine decanoate can be administered subcutaneously, using a 5/8-inch, 22-gauge needle for patients who fear long needles or are exquisitely sensitive to pain. IM administration is required for haloperidol decanoate, however.

50 vs. 100 mg/cc

Choice of preparation can also promote post-injection comfort. I have heard patients occasionally complain of lingering muscular discomfort after receiving the 100 mg/cc haloperidol decanoate preparation, but I have never heard such complaints after administering haloperidol, 50 mg/cc, or fluphenazine, 25 mg/cc.

Drug brand names

• Fluphenazine • Prolixin
• Haloperidol • Haldol

Long-acting intramuscular (IM) antipsychotics are necessary for patients who do not respond to—or comply with—oral medication regimens. We can make these injections less painful, provided that agitation does not complicate treatment.

In 25 years of practice, I’ve discovered the following ways to diminish the pain of injection:

• Inject into the deltoid’s posterior aspect. Nociceptive pain fibers may be less dense in the posterior versus the anterior deltoid. I try to inject latitudinally about 1 cm behind the deltoid midline and longitudinally about 5 cm below the acromioclavicular joint.
• Inject into the lateral gluteusto avoid stimulating the sciatic nerve that runs down the medial gluteus.
• Have the patient fold his or her arm across the lap.Muscles that are relaxed before injection are less likely to hurt afterward. The arm’s flexed position will help relax the deltoid.
• Massage the muscle area overlying the injection sitefor about 10 seconds before injecting. This further relaxes the muscle.
• Inject slowly—about 30 seconds per cc. A faster injection can increase pain.
• Inject air into the vial before withdrawing. Commonly used injectable psychiatric drugs are based in sesame oil. Withdrawing these viscous medications through the perforation site can be difficult if the vial is partially evacuated and the remaining fluid is under negative atmospheric pressure.

Some clinicians use the “Z technique” to prevent backflow when injecting IM antipsychotics. With this method, skin and subcutaneous tissue are retracted to avoid creating a straight-line needle tract that would allow the ready backflow of injected material.

I feel this method is unnecessary for decanoate preparations; they are viscous enough to prevent significant backflow provided the injection is slowly administered.

To IM or not to IM

Where possible, administering medications subcutaneously instead of intramuscularly can also reduce pain.

Contrary to popular belief, fluphenazine decanoate can be administered subcutaneously, using a 5/8-inch, 22-gauge needle for patients who fear long needles or are exquisitely sensitive to pain. IM administration is required for haloperidol decanoate, however.

50 vs. 100 mg/cc

Choice of preparation can also promote post-injection comfort. I have heard patients occasionally complain of lingering muscular discomfort after receiving the 100 mg/cc haloperidol decanoate preparation, but I have never heard such complaints after administering haloperidol, 50 mg/cc, or fluphenazine, 25 mg/cc.

Drug brand names

• Fluphenazine • Prolixin
• Haloperidol • Haldol

Long-acting intramuscular (IM) antipsychotics are necessary for patients who do not respond to—or comply with—oral medication regimens. We can make these injections less painful, provided that agitation does not complicate treatment.

In 25 years of practice, I’ve discovered the following ways to diminish the pain of injection:

• Inject into the deltoid’s posterior aspect. Nociceptive pain fibers may be less dense in the posterior versus the anterior deltoid. I try to inject latitudinally about 1 cm behind the deltoid midline and longitudinally about 5 cm below the acromioclavicular joint.
• Inject into the lateral gluteusto avoid stimulating the sciatic nerve that runs down the medial gluteus.
• Have the patient fold his or her arm across the lap.Muscles that are relaxed before injection are less likely to hurt afterward. The arm’s flexed position will help relax the deltoid.
• Massage the muscle area overlying the injection sitefor about 10 seconds before injecting. This further relaxes the muscle.
• Inject slowly—about 30 seconds per cc. A faster injection can increase pain.
• Inject air into the vial before withdrawing. Commonly used injectable psychiatric drugs are based in sesame oil. Withdrawing these viscous medications through the perforation site can be difficult if the vial is partially evacuated and the remaining fluid is under negative atmospheric pressure.

Some clinicians use the “Z technique” to prevent backflow when injecting IM antipsychotics. With this method, skin and subcutaneous tissue are retracted to avoid creating a straight-line needle tract that would allow the ready backflow of injected material.

I feel this method is unnecessary for decanoate preparations; they are viscous enough to prevent significant backflow provided the injection is slowly administered.

To IM or not to IM

Where possible, administering medications subcutaneously instead of intramuscularly can also reduce pain.

Contrary to popular belief, fluphenazine decanoate can be administered subcutaneously, using a 5/8-inch, 22-gauge needle for patients who fear long needles or are exquisitely sensitive to pain. IM administration is required for haloperidol decanoate, however.

50 vs. 100 mg/cc

Choice of preparation can also promote post-injection comfort. I have heard patients occasionally complain of lingering muscular discomfort after receiving the 100 mg/cc haloperidol decanoate preparation, but I have never heard such complaints after administering haloperidol, 50 mg/cc, or fluphenazine, 25 mg/cc.

Drug brand names

• Fluphenazine • Prolixin
• Haloperidol • Haldol

In your “Cases That Test Your Skills” article on Charles Bonnet syndrome (CBS) (Current Psychiatry, May 2003), the authors briefly mention substance-induced psychosis in the differential diagnosis of visual hallucinations.

Ms. K was taking two antimuscarinic drugs, tolterodine and oxybutynin; I would not have accepted CBS as a diagnosis until the role of these drugs was clarified.

One patient developed visual hallucinations when her urologist started her on imipramine for urinary incontinence. Interestingly, once she was reassured that imipramine was causing this effect, she chose to keep taking it. She preferred occasional hallucinations to incontinence.

William Braden MD
Providence, RI

The authors did not adequately consider anticholinergic toxicity from a longstanding medication regimen as a possible cause of Ms. K’s visual hallucinations.

It is true that Ms. K had been taking tolterodine and oxybutynin, both anticholinergic agents, for more than 2 years without apparent adverse effects. However, that does not rule out the possibility that her advancing age and other factors increased her vulnerability to such toxicity. While her normal Mini-Mental State Examination score and clear sensorium do rule out frank delirium, anticholinergic toxicity can occur without gross cognitive impairment.

Robert L. Marcus, MD
Dix Hills, NY

The author responds

Drs. Braden and Marcus raise valid concerns about the effects of tolterodine and oxybutynin on Ms. K’s visual hallucinations. Benzodiazepines, tricyclic antidepressants, analgesics, beta-blockers, and antimuscarinics have all been linked to substance-induced psychosis, particularly in older patients.

We felt comfortable excluding these medications as playing a role in Ms. K’s visual hallucinations. She had tolerated these agents well with no changes for more than 2 years, so visual hallucinations as a sudden adverse effect seemed unlikely. Looking back, maybe anticholinergic toxicity could have been considered as a possible cause.

Drs. Braden and Marcus remind us that when evaluating apparent psychosis in older psychiatric patients, we should rule out causes such as medications and illegal substances. When alternative explanations are exhausted, however, a diagnosis of CBS may be warranted in the visually impaired patient who retains cognitive function.

Lee I. Kubersky
Third-year medical student
University of Medicine and Dentistry of New Jersey
Cooper Hospital/University Medical Center
Camden, NJ

In your “Cases That Test Your Skills” article on Charles Bonnet syndrome (CBS) (Current Psychiatry, May 2003), the authors briefly mention substance-induced psychosis in the differential diagnosis of visual hallucinations.

Ms. K was taking two antimuscarinic drugs, tolterodine and oxybutynin; I would not have accepted CBS as a diagnosis until the role of these drugs was clarified.

One patient developed visual hallucinations when her urologist started her on imipramine for urinary incontinence. Interestingly, once she was reassured that imipramine was causing this effect, she chose to keep taking it. She preferred occasional hallucinations to incontinence.

William Braden MD
Providence, RI

The authors did not adequately consider anticholinergic toxicity from a longstanding medication regimen as a possible cause of Ms. K’s visual hallucinations.

It is true that Ms. K had been taking tolterodine and oxybutynin, both anticholinergic agents, for more than 2 years without apparent adverse effects. However, that does not rule out the possibility that her advancing age and other factors increased her vulnerability to such toxicity. While her normal Mini-Mental State Examination score and clear sensorium do rule out frank delirium, anticholinergic toxicity can occur without gross cognitive impairment.

Robert L. Marcus, MD
Dix Hills, NY

The author responds

Drs. Braden and Marcus raise valid concerns about the effects of tolterodine and oxybutynin on Ms. K’s visual hallucinations. Benzodiazepines, tricyclic antidepressants, analgesics, beta-blockers, and antimuscarinics have all been linked to substance-induced psychosis, particularly in older patients.

We felt comfortable excluding these medications as playing a role in Ms. K’s visual hallucinations. She had tolerated these agents well with no changes for more than 2 years, so visual hallucinations as a sudden adverse effect seemed unlikely. Looking back, maybe anticholinergic toxicity could have been considered as a possible cause.

Drs. Braden and Marcus remind us that when evaluating apparent psychosis in older psychiatric patients, we should rule out causes such as medications and illegal substances. When alternative explanations are exhausted, however, a diagnosis of CBS may be warranted in the visually impaired patient who retains cognitive function.

Lee I. Kubersky
Third-year medical student
University of Medicine and Dentistry of New Jersey
Cooper Hospital/University Medical Center
Camden, NJ

In your “Cases That Test Your Skills” article on Charles Bonnet syndrome (CBS) (Current Psychiatry, May 2003), the authors briefly mention substance-induced psychosis in the differential diagnosis of visual hallucinations.

Ms. K was taking two antimuscarinic drugs, tolterodine and oxybutynin; I would not have accepted CBS as a diagnosis until the role of these drugs was clarified.

One patient developed visual hallucinations when her urologist started her on imipramine for urinary incontinence. Interestingly, once she was reassured that imipramine was causing this effect, she chose to keep taking it. She preferred occasional hallucinations to incontinence.

William Braden MD
Providence, RI

The authors did not adequately consider anticholinergic toxicity from a longstanding medication regimen as a possible cause of Ms. K’s visual hallucinations.

It is true that Ms. K had been taking tolterodine and oxybutynin, both anticholinergic agents, for more than 2 years without apparent adverse effects. However, that does not rule out the possibility that her advancing age and other factors increased her vulnerability to such toxicity. While her normal Mini-Mental State Examination score and clear sensorium do rule out frank delirium, anticholinergic toxicity can occur without gross cognitive impairment.

Robert L. Marcus, MD
Dix Hills, NY

The author responds

Drs. Braden and Marcus raise valid concerns about the effects of tolterodine and oxybutynin on Ms. K’s visual hallucinations. Benzodiazepines, tricyclic antidepressants, analgesics, beta-blockers, and antimuscarinics have all been linked to substance-induced psychosis, particularly in older patients.

We felt comfortable excluding these medications as playing a role in Ms. K’s visual hallucinations. She had tolerated these agents well with no changes for more than 2 years, so visual hallucinations as a sudden adverse effect seemed unlikely. Looking back, maybe anticholinergic toxicity could have been considered as a possible cause.

Drs. Braden and Marcus remind us that when evaluating apparent psychosis in older psychiatric patients, we should rule out causes such as medications and illegal substances. When alternative explanations are exhausted, however, a diagnosis of CBS may be warranted in the visually impaired patient who retains cognitive function.

Lee I. Kubersky
Third-year medical student
University of Medicine and Dentistry of New Jersey
Cooper Hospital/University Medical Center
Camden, NJ

Psychiatrists often treat patients with irritable bowel syndrome (IBS) and an accompanying mental illness. Knowledge of available treatments and communication with the referring doctor are crucial to treating both the IBS symptoms and the comorbidity.

This article presents three cases that illustrate the challenges of identifying target symptoms, avoiding drug-drug interactions, ruling out serious underlying medical problems, and formulating treatment.

WHO GETS IBS?

Approximately 12% of the United States population reports IBS symptoms (abdominal pain, bloating, altered bowel habits).¹ These symptoms begin before age 35 in most patients and during childhood in some. Onset after age 65 is rare.

IBS is common among patients with alcohol abuse disorder (32%),² chronic fatigue syndrome (92%), fibromyalgia (77%), or temporomandibular joint syndrome (64%).³ Seventy percent of patients with IBS are women.⁴ Chronic pelvic pain, dyspareunia, dysmenorrhea, or a history of abdominal surgeries are risk factors for IBS in women.

LINK BETWEEN IBS AND MENTAL ILLNESS

Although mental illness often coexists with IBS, no cause-effect relationship has been shown.⁵

IBS is often preceded by stressful life events, such as family death or divorce,³ and some believe IBS is a precursor to numerous psychiatric disorders. Generalized anxiety disorder, major depression, panic disorder, social phobia, somatization disorder, or dysthymia have been diagnosed in most IBS patients.²

CASE 1: IBS AND DEPRESSION

Ms. R, age 55, has had IBS for 10 years. She has occasional diarrhea and abdominal cramps relieved by bowel movements. She is taking a bulking agent but still sometimes suffers abdominal pain.

She is referred to a psychiatrist after complaining of fatigue, loss of interest in hobbies, and crying spells for 2 months. She denies suicidal ideations. Her referring physician reports that she is taking conjugated estrogens to manage menopause symptoms. She denies any recent stressful life events. Thyroid function, glucose, and CBC are normal.

The challenge: Deciding which to treat first—the IBS symptoms or the depression—and how.

Discussion: The predominant symptom (in Ms. R’s case, abdominal pain) can help determine choice of medication. Bulk-forming agents, antispasmodics, barbiturates, benzodiazepines, and serotonin reuptake inhibitors have historically been used to treat IBS,⁶ but scant evidence supports their use.

Obtaining a thorough prescription history from the primary care physician, OB/GYN, and other treatment team members is critical before formulating a treatment plan. Ms. R’s estrogen use will not affect the choice of psychotropic or IBS medication because there are no significant interactions between estrogen and these classes of drugs.

Ms. R’s abdominal pain and depression can be treated simultaneously. Randomized, controlled trials have demonstrated that tricyclic antidepressants reduce abdominal pain and that behavioral therapy (relaxation therapy, hypnotherapy, and cognitive-behavioral therapy) may relieve individual IBS symptoms.⁷

Case 1 concluded: After reviewing Ms. R’s medications, the psychiatrist starts:

• desipramine, 50 mg at bedtime, to minimize anticholinergic side effects
• and short-term psychotherapy, which helped her identify support mechanisms and ways to better balance her life stresses.

After 6 weeks, her Beck Depression Inventory score improved from 30 at baseline to 8. She reports her abdominal pain is “the best it has been in 10 years.” Six months after diagnosis, she continues to take desipramine and is doing well.

CASE 2: IBS, DEPRESSION, AND PSYCHOSIS

Ms. H, age 32, is referred to a psychiatrist for treatment of depression with paranoid features.

Four years ago, a gastroenterologist diagnosed her as having IBS. She experiences frequent diarrhea and lower abdominal cramping. For 2 years she has been taking the antimuscarinic dicyclomine, 10 mg tid, which has provided some relief from her cramps. An estimated 20 diarrhea attacks per day leaves her housebound much of the time, however.

She reports fatigue, loss of interest in hobbies across 2 months, and paranoid thinking. She denies hallucinations or delusions but believes that her teenage children are discussing her “sickness” and plotting to “drive her crazy.” She is not suicidal.

The challenge: Treating Ms. H’s depression and paranoia while avoiding drug-drug interactions.

Discussion: Adverse drug-drug interactions can occur when prescribing psychotropics to patients with IBS (Table 1). Additive constipation, diarrhea, abdominal pain, and sedation are common interactions between psychotropics and the 5-HT3 antagonists and 5HT4 agonists commonly prescribed for IBS.

Table 1

Interactions between psychotropics and agents prescribed for IBS

Box

Other than fiber supplements, most traditional IBS medications are sedating and are associated with anticholinergic side effects. In Ms. H’s case, extreme caution is necessary before prescribing an antidepressant or antipsychotic because of dicyclomine’s additive sedating effects.

Case 2 concluded: After a thorough initial patient interview, the psychiatrist elects to treat Ms. H’s major depression with an antidepressant but delays the use of an antipsychotic to avoid additive sedation.

After talking with Ms. H’s family physician, the psychiatrist stops her dicyclomine and starts sertraline, 100 mg/d. She tolerates the sertraline well and the dosage is titrated across 1 month to 200 mg/d.

Four weeks later, Ms. H’s Beck Depression Inventory score has improved from 26 at baseline to 5, but her paranoid thoughts and frequent diarrhea persist. The psychiatrist adds low-dose olanzapine (5 mg at bedtime) to minimize extrapyramidal side effects. One month later, her depression and paranoia have resolved.

Ms. H’s gastroenterologist instructs her to begin taking alosetron, 1 mg bid, for her continued frequent diarrhea. Adding this agent to her sertraline/olanzapine regimen can lead to additive constipation and abdominal pain, so the psychiatrist monitors her psychiatric medications. One month later, she reports that her affect is much improved and her diarrhea is “gone.”

CASE 3: DEPRESSION AND ABDOMINAL PAIN

Mr. J, age 52, has had depression for 1 year. His depressive symptoms have improved significantly on fluoxetine, 20 mg/d; he once again enjoys life and has a more positive outlook.

The patient was in reasonably good health until about 1 month ago, when he began to experience abdominal pain. He has lost 14 lbs over the past month. He is not taking other medications.

The challenge: Find the cause of Mr. J’s persistent abdominal pain without undermining depression therapy.

Discussion: Although Mr. J’s symptoms might be side effects of fluoxetine, his abdominal pain and weight loss >10 lbs within 1 month are cause for concern. The American College of Gastroenterology has identified six alarm symptoms that could point to a serious medical problem in patients with severe abdominal pain (Box).⁷

Patients who exhibit any of these symptoms should be referred for endoscopic and stool studies. Colon cancer screening should be considered for all patients age 50 and older.

Patients with IBS usually present first to their primary care physicians with abdominal pain and altered bowel habits. These symptoms can occur in many gastrointestinal and systemic illnesses (Table 2).⁸

Table 2

Diagnosing irritable bowel syndrome: What to rule out

Case 3 concluded: The psychiatrist and primary care physician consult a gastroenterologist, who performs a colonoscopy and identifies a resectable Duke’s Class B adenocarcinoma in the transverse colon. A partial colectomy is performed.

Three years later, Mr. J is cancer-free and his depression is stable. The psychiatrist advises him to keep taking fluoxetine, 20 mg/d, because the stress of his cancer therapy increases the risk of depression recurrence.

Related resources

• National Institute of Diabetes and Digestive and Kidney Diseases —Irritable Bowel Syndrome www.niddk.nih.gov/health/digest/pubs/irrbowel/irrbowel.htm

Drug brand names

• Alosetron • Lotronex
• Aripiprazole • Abilify
• Buspirone • BuSpar
• Desipramine • Norpramin
• Dicyclomine • Bentyl
• Fluoxetine • Prozac
• Olanzapine • Zyprexa
• Sertraline • Zoloft

Disclosure

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

Psychiatrists often treat patients with irritable bowel syndrome (IBS) and an accompanying mental illness. Knowledge of available treatments and communication with the referring doctor are crucial to treating both the IBS symptoms and the comorbidity.

This article presents three cases that illustrate the challenges of identifying target symptoms, avoiding drug-drug interactions, ruling out serious underlying medical problems, and formulating treatment.

WHO GETS IBS?

Approximately 12% of the United States population reports IBS symptoms (abdominal pain, bloating, altered bowel habits).¹ These symptoms begin before age 35 in most patients and during childhood in some. Onset after age 65 is rare.

IBS is common among patients with alcohol abuse disorder (32%),² chronic fatigue syndrome (92%), fibromyalgia (77%), or temporomandibular joint syndrome (64%).³ Seventy percent of patients with IBS are women.⁴ Chronic pelvic pain, dyspareunia, dysmenorrhea, or a history of abdominal surgeries are risk factors for IBS in women.

LINK BETWEEN IBS AND MENTAL ILLNESS

Although mental illness often coexists with IBS, no cause-effect relationship has been shown.⁵

IBS is often preceded by stressful life events, such as family death or divorce,³ and some believe IBS is a precursor to numerous psychiatric disorders. Generalized anxiety disorder, major depression, panic disorder, social phobia, somatization disorder, or dysthymia have been diagnosed in most IBS patients.²

CASE 1: IBS AND DEPRESSION

Ms. R, age 55, has had IBS for 10 years. She has occasional diarrhea and abdominal cramps relieved by bowel movements. She is taking a bulking agent but still sometimes suffers abdominal pain.

She is referred to a psychiatrist after complaining of fatigue, loss of interest in hobbies, and crying spells for 2 months. She denies suicidal ideations. Her referring physician reports that she is taking conjugated estrogens to manage menopause symptoms. She denies any recent stressful life events. Thyroid function, glucose, and CBC are normal.

The challenge: Deciding which to treat first—the IBS symptoms or the depression—and how.

Discussion: The predominant symptom (in Ms. R’s case, abdominal pain) can help determine choice of medication. Bulk-forming agents, antispasmodics, barbiturates, benzodiazepines, and serotonin reuptake inhibitors have historically been used to treat IBS,⁶ but scant evidence supports their use.

Obtaining a thorough prescription history from the primary care physician, OB/GYN, and other treatment team members is critical before formulating a treatment plan. Ms. R’s estrogen use will not affect the choice of psychotropic or IBS medication because there are no significant interactions between estrogen and these classes of drugs.

Ms. R’s abdominal pain and depression can be treated simultaneously. Randomized, controlled trials have demonstrated that tricyclic antidepressants reduce abdominal pain and that behavioral therapy (relaxation therapy, hypnotherapy, and cognitive-behavioral therapy) may relieve individual IBS symptoms.⁷

Case 1 concluded: After reviewing Ms. R’s medications, the psychiatrist starts:

• desipramine, 50 mg at bedtime, to minimize anticholinergic side effects
• and short-term psychotherapy, which helped her identify support mechanisms and ways to better balance her life stresses.

After 6 weeks, her Beck Depression Inventory score improved from 30 at baseline to 8. She reports her abdominal pain is “the best it has been in 10 years.” Six months after diagnosis, she continues to take desipramine and is doing well.

CASE 2: IBS, DEPRESSION, AND PSYCHOSIS

Ms. H, age 32, is referred to a psychiatrist for treatment of depression with paranoid features.

Four years ago, a gastroenterologist diagnosed her as having IBS. She experiences frequent diarrhea and lower abdominal cramping. For 2 years she has been taking the antimuscarinic dicyclomine, 10 mg tid, which has provided some relief from her cramps. An estimated 20 diarrhea attacks per day leaves her housebound much of the time, however.

She reports fatigue, loss of interest in hobbies across 2 months, and paranoid thinking. She denies hallucinations or delusions but believes that her teenage children are discussing her “sickness” and plotting to “drive her crazy.” She is not suicidal.

The challenge: Treating Ms. H’s depression and paranoia while avoiding drug-drug interactions.

Discussion: Adverse drug-drug interactions can occur when prescribing psychotropics to patients with IBS (Table 1). Additive constipation, diarrhea, abdominal pain, and sedation are common interactions between psychotropics and the 5-HT3 antagonists and 5HT4 agonists commonly prescribed for IBS.

Table 1

Interactions between psychotropics and agents prescribed for IBS

Box

Other than fiber supplements, most traditional IBS medications are sedating and are associated with anticholinergic side effects. In Ms. H’s case, extreme caution is necessary before prescribing an antidepressant or antipsychotic because of dicyclomine’s additive sedating effects.

Case 2 concluded: After a thorough initial patient interview, the psychiatrist elects to treat Ms. H’s major depression with an antidepressant but delays the use of an antipsychotic to avoid additive sedation.

After talking with Ms. H’s family physician, the psychiatrist stops her dicyclomine and starts sertraline, 100 mg/d. She tolerates the sertraline well and the dosage is titrated across 1 month to 200 mg/d.

Four weeks later, Ms. H’s Beck Depression Inventory score has improved from 26 at baseline to 5, but her paranoid thoughts and frequent diarrhea persist. The psychiatrist adds low-dose olanzapine (5 mg at bedtime) to minimize extrapyramidal side effects. One month later, her depression and paranoia have resolved.

Ms. H’s gastroenterologist instructs her to begin taking alosetron, 1 mg bid, for her continued frequent diarrhea. Adding this agent to her sertraline/olanzapine regimen can lead to additive constipation and abdominal pain, so the psychiatrist monitors her psychiatric medications. One month later, she reports that her affect is much improved and her diarrhea is “gone.”

CASE 3: DEPRESSION AND ABDOMINAL PAIN

Mr. J, age 52, has had depression for 1 year. His depressive symptoms have improved significantly on fluoxetine, 20 mg/d; he once again enjoys life and has a more positive outlook.

The patient was in reasonably good health until about 1 month ago, when he began to experience abdominal pain. He has lost 14 lbs over the past month. He is not taking other medications.

The challenge: Find the cause of Mr. J’s persistent abdominal pain without undermining depression therapy.

Discussion: Although Mr. J’s symptoms might be side effects of fluoxetine, his abdominal pain and weight loss >10 lbs within 1 month are cause for concern. The American College of Gastroenterology has identified six alarm symptoms that could point to a serious medical problem in patients with severe abdominal pain (Box).⁷

Patients who exhibit any of these symptoms should be referred for endoscopic and stool studies. Colon cancer screening should be considered for all patients age 50 and older.

Patients with IBS usually present first to their primary care physicians with abdominal pain and altered bowel habits. These symptoms can occur in many gastrointestinal and systemic illnesses (Table 2).⁸

Table 2

Diagnosing irritable bowel syndrome: What to rule out

Case 3 concluded: The psychiatrist and primary care physician consult a gastroenterologist, who performs a colonoscopy and identifies a resectable Duke’s Class B adenocarcinoma in the transverse colon. A partial colectomy is performed.

Three years later, Mr. J is cancer-free and his depression is stable. The psychiatrist advises him to keep taking fluoxetine, 20 mg/d, because the stress of his cancer therapy increases the risk of depression recurrence.

Related resources

• National Institute of Diabetes and Digestive and Kidney Diseases —Irritable Bowel Syndrome www.niddk.nih.gov/health/digest/pubs/irrbowel/irrbowel.htm

Drug brand names

• Alosetron • Lotronex
• Aripiprazole • Abilify
• Buspirone • BuSpar
• Desipramine • Norpramin
• Dicyclomine • Bentyl
• Fluoxetine • Prozac
• Olanzapine • Zyprexa
• Sertraline • Zoloft

Disclosure

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

Psychiatrists often treat patients with irritable bowel syndrome (IBS) and an accompanying mental illness. Knowledge of available treatments and communication with the referring doctor are crucial to treating both the IBS symptoms and the comorbidity.

This article presents three cases that illustrate the challenges of identifying target symptoms, avoiding drug-drug interactions, ruling out serious underlying medical problems, and formulating treatment.

WHO GETS IBS?

Approximately 12% of the United States population reports IBS symptoms (abdominal pain, bloating, altered bowel habits).¹ These symptoms begin before age 35 in most patients and during childhood in some. Onset after age 65 is rare.

IBS is common among patients with alcohol abuse disorder (32%),² chronic fatigue syndrome (92%), fibromyalgia (77%), or temporomandibular joint syndrome (64%).³ Seventy percent of patients with IBS are women.⁴ Chronic pelvic pain, dyspareunia, dysmenorrhea, or a history of abdominal surgeries are risk factors for IBS in women.

LINK BETWEEN IBS AND MENTAL ILLNESS

Although mental illness often coexists with IBS, no cause-effect relationship has been shown.⁵

IBS is often preceded by stressful life events, such as family death or divorce,³ and some believe IBS is a precursor to numerous psychiatric disorders. Generalized anxiety disorder, major depression, panic disorder, social phobia, somatization disorder, or dysthymia have been diagnosed in most IBS patients.²

CASE 1: IBS AND DEPRESSION

Ms. R, age 55, has had IBS for 10 years. She has occasional diarrhea and abdominal cramps relieved by bowel movements. She is taking a bulking agent but still sometimes suffers abdominal pain.

She is referred to a psychiatrist after complaining of fatigue, loss of interest in hobbies, and crying spells for 2 months. She denies suicidal ideations. Her referring physician reports that she is taking conjugated estrogens to manage menopause symptoms. She denies any recent stressful life events. Thyroid function, glucose, and CBC are normal.

The challenge: Deciding which to treat first—the IBS symptoms or the depression—and how.

Discussion: The predominant symptom (in Ms. R’s case, abdominal pain) can help determine choice of medication. Bulk-forming agents, antispasmodics, barbiturates, benzodiazepines, and serotonin reuptake inhibitors have historically been used to treat IBS,⁶ but scant evidence supports their use.

Obtaining a thorough prescription history from the primary care physician, OB/GYN, and other treatment team members is critical before formulating a treatment plan. Ms. R’s estrogen use will not affect the choice of psychotropic or IBS medication because there are no significant interactions between estrogen and these classes of drugs.

Ms. R’s abdominal pain and depression can be treated simultaneously. Randomized, controlled trials have demonstrated that tricyclic antidepressants reduce abdominal pain and that behavioral therapy (relaxation therapy, hypnotherapy, and cognitive-behavioral therapy) may relieve individual IBS symptoms.⁷

Case 1 concluded: After reviewing Ms. R’s medications, the psychiatrist starts:

• desipramine, 50 mg at bedtime, to minimize anticholinergic side effects
• and short-term psychotherapy, which helped her identify support mechanisms and ways to better balance her life stresses.

After 6 weeks, her Beck Depression Inventory score improved from 30 at baseline to 8. She reports her abdominal pain is “the best it has been in 10 years.” Six months after diagnosis, she continues to take desipramine and is doing well.

CASE 2: IBS, DEPRESSION, AND PSYCHOSIS

Ms. H, age 32, is referred to a psychiatrist for treatment of depression with paranoid features.

Four years ago, a gastroenterologist diagnosed her as having IBS. She experiences frequent diarrhea and lower abdominal cramping. For 2 years she has been taking the antimuscarinic dicyclomine, 10 mg tid, which has provided some relief from her cramps. An estimated 20 diarrhea attacks per day leaves her housebound much of the time, however.

She reports fatigue, loss of interest in hobbies across 2 months, and paranoid thinking. She denies hallucinations or delusions but believes that her teenage children are discussing her “sickness” and plotting to “drive her crazy.” She is not suicidal.

The challenge: Treating Ms. H’s depression and paranoia while avoiding drug-drug interactions.

Discussion: Adverse drug-drug interactions can occur when prescribing psychotropics to patients with IBS (Table 1). Additive constipation, diarrhea, abdominal pain, and sedation are common interactions between psychotropics and the 5-HT3 antagonists and 5HT4 agonists commonly prescribed for IBS.

Table 1

Interactions between psychotropics and agents prescribed for IBS

Box

Other than fiber supplements, most traditional IBS medications are sedating and are associated with anticholinergic side effects. In Ms. H’s case, extreme caution is necessary before prescribing an antidepressant or antipsychotic because of dicyclomine’s additive sedating effects.

Case 2 concluded: After a thorough initial patient interview, the psychiatrist elects to treat Ms. H’s major depression with an antidepressant but delays the use of an antipsychotic to avoid additive sedation.

After talking with Ms. H’s family physician, the psychiatrist stops her dicyclomine and starts sertraline, 100 mg/d. She tolerates the sertraline well and the dosage is titrated across 1 month to 200 mg/d.

Four weeks later, Ms. H’s Beck Depression Inventory score has improved from 26 at baseline to 5, but her paranoid thoughts and frequent diarrhea persist. The psychiatrist adds low-dose olanzapine (5 mg at bedtime) to minimize extrapyramidal side effects. One month later, her depression and paranoia have resolved.

Ms. H’s gastroenterologist instructs her to begin taking alosetron, 1 mg bid, for her continued frequent diarrhea. Adding this agent to her sertraline/olanzapine regimen can lead to additive constipation and abdominal pain, so the psychiatrist monitors her psychiatric medications. One month later, she reports that her affect is much improved and her diarrhea is “gone.”

CASE 3: DEPRESSION AND ABDOMINAL PAIN

Mr. J, age 52, has had depression for 1 year. His depressive symptoms have improved significantly on fluoxetine, 20 mg/d; he once again enjoys life and has a more positive outlook.

The patient was in reasonably good health until about 1 month ago, when he began to experience abdominal pain. He has lost 14 lbs over the past month. He is not taking other medications.

The challenge: Find the cause of Mr. J’s persistent abdominal pain without undermining depression therapy.

Discussion: Although Mr. J’s symptoms might be side effects of fluoxetine, his abdominal pain and weight loss >10 lbs within 1 month are cause for concern. The American College of Gastroenterology has identified six alarm symptoms that could point to a serious medical problem in patients with severe abdominal pain (Box).⁷

Patients who exhibit any of these symptoms should be referred for endoscopic and stool studies. Colon cancer screening should be considered for all patients age 50 and older.

Patients with IBS usually present first to their primary care physicians with abdominal pain and altered bowel habits. These symptoms can occur in many gastrointestinal and systemic illnesses (Table 2).⁸

Table 2

Diagnosing irritable bowel syndrome: What to rule out

Case 3 concluded: The psychiatrist and primary care physician consult a gastroenterologist, who performs a colonoscopy and identifies a resectable Duke’s Class B adenocarcinoma in the transverse colon. A partial colectomy is performed.

Three years later, Mr. J is cancer-free and his depression is stable. The psychiatrist advises him to keep taking fluoxetine, 20 mg/d, because the stress of his cancer therapy increases the risk of depression recurrence.

Related resources

• National Institute of Diabetes and Digestive and Kidney Diseases —Irritable Bowel Syndrome www.niddk.nih.gov/health/digest/pubs/irrbowel/irrbowel.htm

Drug brand names

• Alosetron • Lotronex
• Aripiprazole • Abilify
• Buspirone • BuSpar
• Desipramine • Norpramin
• Dicyclomine • Bentyl
• Fluoxetine • Prozac
• Olanzapine • Zyprexa
• Sertraline • Zoloft

Disclosure

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

In patients with psychotic symptoms, why are African-Americans more likely than whites to be diagnosed with schizophrenia? After more than 30 years of debate, some answers—and remedies for the problem—are becoming clear.

In psychiatry, where interpersonal interactions are key to eliciting diagnostic symptoms and signs, there is an intrinsic risk of misinterpretation when clinician and patient are of different cultural, ethnic, or socioeconomic backgrounds. This article analyzes four factors that contribute to misinterpretation and to ethnic misdiagnosis of schizophrenia. Culturally sensitive strategies are offered to avoid diagnostic bias in clinical practice.

SCHIZOPHRENIA MISDIAGNOSIS

Large epidemiologic studies report similar rates of schizophrenia and bipolar disorder in African-American and white populations.¹ Although patients of both races have been wrongly diagnosed with schizophrenia, the pattern is stronger and more persistent in African-Americans.

Box 1

In the 1970s, Simon et al² studied 192 hospitalized patients, of whom all African-Americans and 85% of whites had been identified clinically as having schizophrenia. Using a structured interview, the researchers found that only 40% of the African Americans and 50% of the whites met diagnostic criteria for schizophrenia. African-Americans with mood disorders were found to be at particular risk of schizophrenia misdiagnosis.

In the 1980s, among 76 patients with a clinical diagnosis of schizophrenia, Mukherjee et al³ diagnosed one-half (52%) with bipolar disorder using a structured clinical interview. Schizophrenia misdiagnoses were more common in African-Americans (86%) and Hispanics (83%) than in whites (51%). In particular, African-Americans were most likely to be misdiagnosed with paranoid schizophrenia. African-Americans complained more commonly than whites of auditory hallucinations, which may represent an ethnic difference in symptomatic presentation of psychotic mood disorders.

In the 1990s, colleagues and I conducted two studies—one of 173 patients in a Tennessee psychiatric hospital⁴ and the other of 490 patients in an Ohio psychiatric emergency service⁵—and found yet again that African-Americans were more likely than whites to be diagnosed with schizophrenia. In the hospital study, higher rates of schizophrenia diagnosis were associated with lower rates of mood disorder diagnosis. This inverse relationship implied that African-Americans with mood disorders were being misdiagnosed with schizophrenia.

Men were more likely than women to be diagnosed with schizophrenia, suggesting that African-American men were most likely to be misdiagnosed. When adjustments were made for gender, black women were found to be at higher risk for misdiagnosis than white women.

Lawson et al⁶ extended this research in a population-based study of African-Americans living in Tennessee. They found that African-Americans constituted 16% of the state’s population but 48% of psychiatric inpatients diagnosed with schizophrenia and 37% of psychiatric outpatients.

CONSEQUENCES OF INACCURATE DIAGNOSIS

Differentiating between schizophrenia (Box 1) and a psychotic mood disorder (Box 2) is more than a semantic exercise. Schizophrenia implies a chronic, unremitting, debilitating illness that worsens over time. Though this perception of schizophrenia is not entirely accurate, in clinical practice its diagnosis imparts a bleak prognosis that may lower the clinician’s expectations for the patient.⁷

Schizophrenia misdiagnosis also may lead the psychiatrist to rely excessively on antipsychotics, rather than attempting thymoleptic and psychotherapy trials. Studies suggest that African-American patients are more likely than similar white patients to receive antipsychotics^4,8,9 and less likely to receive psychotherapy.^5,10

Reasons why African-Americans are often misdiagnosed with schizophrenia remain unclear but probably include four contributing factors:

• differences in symptom presentation compared with whites
• failure by clinicians to identify affective symptoms in African-Americans
• minority patients’ wariness when dealing with health services
• and racial stereotyping.

DIFFERENCES IN SYMPTOM EXPRESSION

African-American patients with mood disorders or schizophrenia are more likely than are similar white patients to complain of auditory hallucinations.^11-13 For example, Strakowski et al¹⁴ examined 330 patients with nonaffective and psychotic diagnoses in a study that was used to develop DSM-IV criteria for schizophrenia. Auditory hallucinations were rated as more severe in African-American than in similar white patients.

Box 2

African-American patients also are more likely than whites to exhibit so-called Schneiderian first-rank symptoms of schizophrenia,¹⁵ including:

• delusions of thought broadcasting or insertion
• auditory hallucinations of voices conversing about the patient in the third person.

These symptoms were once used to diagnose schizophrenia, but their lack of specificity has been well documented.^2,16 First-rank symptoms of schizophrenia depend on the specific form of the hallucination or delusion, are likely to be influenced by a patient’s culture, and may be misleading in multicultural populations. Though first-rank symptoms now occupy a minor role in U.S. diagnostic systems, they might continue to sway clinicians—even when using structured diagnostic interviews—to inappropriately diagnose schizophrenia in lieu of affective disorders in minority patients.¹⁵

To extend this finding, our group¹⁶ studied rates and severity of affective and psychotic symptoms—particularly first-rank symptoms—in 100 patients with psychotic mania who met DSM-III-R criteria for bipolar disorder (80%) or schizoaffective disorder, bipolar type (20%) as determined by structured diagnostic interview. No differences in affective symptoms between African-American and white patients were seen. African-Americans were more likely to endorse auditory hallucinations and to report severe auditory hallucinations of voices commenting on their behavior—the only first-rank symptom on which they differed from whites.

Though their affective symptoms were similar, African-Americans were significantly more likely than whites to have been diagnosed with a schizophrenia-spectrum disorder. Because misdiagnosis of African-Americans could not be explained by psychotic symptoms—which were as severe as those of white patients—these findings suggest other mechanisms were at work.

UNIDENTIFIED AFFECTIVE SYMPTOMS

Underidentification of mood disorders in African-American patients may also lead to over-diagnosis of schizophrenia. In a sample of 99 patients, colleagues and I¹⁷ compared clinical diagnoses made in a psychiatric emergency service with those by research investigators using a structured clinical interview. Reasons for diagnostic differences were identified and divided into two categories:

• the same symptoms were recorded but applied differently to diagnostic criteria (criterion variance)
• different information was recorded, which led to diagnostic discrepancies (information variance).

Differences occurred significantly more often in African-American than in white patients, but only information variance was associated with ethnicity. This suggests that clinicians are less likely to elicit appropriate information from African-American than from white psychiatric patients. The fact that researchers obtained this information during diagnostic interviews suggests that the patients could provide it when given appropriate prompts. Specifically, affective symptoms were less likely to be elicited by clinicians than by researchers.

PATIENT WARINESS

Minority patients, when interacting with clinicians of the majority population, may project “protective wariness.”¹⁸ Specific behaviors include hesitancy or reluctance to fully engage with the care provider as a precaution against being exploited or harmed. Cultural misunderstandings¹⁹ and patient concerns about past reports of minorities receiving substandard or unethical health care²⁰ may contribute to this behavior.

Whaley²¹ compared nonpathologic distrust and paranoia in 404 community-living African-Americans and whites. Some were healthy, and some had diagnoses of schizophrenia or depression. African-Americans—particularly those with psychiatric disorders—showed higher levels of distrust than whites. Distrust was also associated with depression in African-Americans but not in whites. Whaley concluded that:

• depressed African-Americans may exhibit more distrust toward clinicians than do whites
• this distrust puts African-Americans at risk of being perceived as paranoid and being misdiagnosed with paranoid schizophrenia.

Table

Remedial actions to avoid ethnic bias in diagnosing schizophrenia

Though Whaley did not report differences in distrust between African-American men and women, others have noted that distrust of health providers may be more common in minority men.¹⁸

RACIAL STEREOTYPING

Compared with similar white men, African-American men with mental disorders are more likely to be:

• referred for mental health care through social and legal—rather than medical—systems and to be involuntarily committed
• perceived as violent—even though controlled research suggests they are not. This misperception can lead to excessive medication and restraints.²²

Differential treatment of African-American men may create a cycle of distrust, hostility, and additional inappropriate treatment. Together, these factors may increase the risk that African-American men will be misdiagnosed with schizophrenia.

Past racism in biomedical and psychiatric practice and research has been documented^23,24 and more recently reviewed by Lawson.¹⁹ Historically, African-Americans were perceived to have a “primitive psychic” nature that was thought to be more susceptible to schizophrenia than depression.¹⁹ Whether these or similar racist stereotypes continue to inject ethnic bias into clinical assessment requires further study.

WHERE DO WE GO FROM HERE?

Although research into methods to eliminate ethnicity bias is sparse, the work reviewed in this article suggests ways that psychiatrists can minimize this problem (Table).

Obtain comprehensive information. Use structured interviews, such as the Structured Clinical Interview for DSM-IV (SCID), and rating scales, such as the Hamilton Depression Scale, which require clinicians to ask about all types of symptoms, particularly affective symptoms.

Review treatment records. Review your practice patterns for evidence of schizophrenia over-diagnosis in African-Americans or other ethnic groups. Examine ethnic differences in legal referrals or use of restraints or seclusion, which may indicate an ethnic bias in how threats are perceived. Only by being aware of bias can one correct it.

Become familiar with cultural and ethnic differences in idioms of distress. Specifically, review research in cultural psychiatry to identify potential differences among cultural groups in how they describe psychiatric symptoms. Talk with colleagues or friends from other cultural groups, and read literature from different ethnic perspectives to increase your cultural sensitivity.

Consult with psychiatrists with expertise in cultural variability of clinical presentation when the diagnosis or threat assessment seems unclear. Consultation is recommended if a patient’s diagnosis is uncertain or if you detect bias in your practice.

These interventions require clinicians to become familiar with psychosocial differences in how patients of various cultural and ethnic groups express psychiatric symptoms. With this understanding, we can better engage wary patients, obtain valid information, and improve clinical practice and patient outcomes.

Finally, psychiatry’s diagnostic systems need to continually address how patient assessment is influenced by ethnicity, culture, gender, and other socio-demographic factors. Studies are needed to examine the contributions of multiple factors—such as symptom differences and stereotyping—that contribute to ethnic-related diagnostic disparities.

Related resources

• Paul AM. Painting insanity black: Why are there more black schizophrenics? Salon.com Dec. 1, 1999. http://www.salon.com/books/it/1999/12/01/schizo/index.html
• Alarcon RD, Westermeyer J, Foulks EF, Ruiz P. Clinical relevance of contemporary cultural psychiatry. J Nerv Ment Dis 1999;187: 465-71.
• Williams DR, Neighbors HW, Jackson JS. Racial/ethnic discrimination and health: findings from community studies. Am J Public Health 2003;93:200-8.
• Lin KM, Smith MW, Ortiz V. Culture and psychopharmacology. Psychiatr Clin North Am 2001; 24:523-38.

Acknowledgement

Preparation of this manuscript was supported in part by National Institutes of Health grant MH56352.

In patients with psychotic symptoms, why are African-Americans more likely than whites to be diagnosed with schizophrenia? After more than 30 years of debate, some answers—and remedies for the problem—are becoming clear.

In psychiatry, where interpersonal interactions are key to eliciting diagnostic symptoms and signs, there is an intrinsic risk of misinterpretation when clinician and patient are of different cultural, ethnic, or socioeconomic backgrounds. This article analyzes four factors that contribute to misinterpretation and to ethnic misdiagnosis of schizophrenia. Culturally sensitive strategies are offered to avoid diagnostic bias in clinical practice.

SCHIZOPHRENIA MISDIAGNOSIS

Large epidemiologic studies report similar rates of schizophrenia and bipolar disorder in African-American and white populations.¹ Although patients of both races have been wrongly diagnosed with schizophrenia, the pattern is stronger and more persistent in African-Americans.

Box 1

In the 1970s, Simon et al² studied 192 hospitalized patients, of whom all African-Americans and 85% of whites had been identified clinically as having schizophrenia. Using a structured interview, the researchers found that only 40% of the African Americans and 50% of the whites met diagnostic criteria for schizophrenia. African-Americans with mood disorders were found to be at particular risk of schizophrenia misdiagnosis.

In the 1980s, among 76 patients with a clinical diagnosis of schizophrenia, Mukherjee et al³ diagnosed one-half (52%) with bipolar disorder using a structured clinical interview. Schizophrenia misdiagnoses were more common in African-Americans (86%) and Hispanics (83%) than in whites (51%). In particular, African-Americans were most likely to be misdiagnosed with paranoid schizophrenia. African-Americans complained more commonly than whites of auditory hallucinations, which may represent an ethnic difference in symptomatic presentation of psychotic mood disorders.

In the 1990s, colleagues and I conducted two studies—one of 173 patients in a Tennessee psychiatric hospital⁴ and the other of 490 patients in an Ohio psychiatric emergency service⁵—and found yet again that African-Americans were more likely than whites to be diagnosed with schizophrenia. In the hospital study, higher rates of schizophrenia diagnosis were associated with lower rates of mood disorder diagnosis. This inverse relationship implied that African-Americans with mood disorders were being misdiagnosed with schizophrenia.

Men were more likely than women to be diagnosed with schizophrenia, suggesting that African-American men were most likely to be misdiagnosed. When adjustments were made for gender, black women were found to be at higher risk for misdiagnosis than white women.

Lawson et al⁶ extended this research in a population-based study of African-Americans living in Tennessee. They found that African-Americans constituted 16% of the state’s population but 48% of psychiatric inpatients diagnosed with schizophrenia and 37% of psychiatric outpatients.

CONSEQUENCES OF INACCURATE DIAGNOSIS

Differentiating between schizophrenia (Box 1) and a psychotic mood disorder (Box 2) is more than a semantic exercise. Schizophrenia implies a chronic, unremitting, debilitating illness that worsens over time. Though this perception of schizophrenia is not entirely accurate, in clinical practice its diagnosis imparts a bleak prognosis that may lower the clinician’s expectations for the patient.⁷

Schizophrenia misdiagnosis also may lead the psychiatrist to rely excessively on antipsychotics, rather than attempting thymoleptic and psychotherapy trials. Studies suggest that African-American patients are more likely than similar white patients to receive antipsychotics^4,8,9 and less likely to receive psychotherapy.^5,10

Reasons why African-Americans are often misdiagnosed with schizophrenia remain unclear but probably include four contributing factors:

• differences in symptom presentation compared with whites
• failure by clinicians to identify affective symptoms in African-Americans
• minority patients’ wariness when dealing with health services
• and racial stereotyping.

DIFFERENCES IN SYMPTOM EXPRESSION

African-American patients with mood disorders or schizophrenia are more likely than are similar white patients to complain of auditory hallucinations.^11-13 For example, Strakowski et al¹⁴ examined 330 patients with nonaffective and psychotic diagnoses in a study that was used to develop DSM-IV criteria for schizophrenia. Auditory hallucinations were rated as more severe in African-American than in similar white patients.

Box 2

African-American patients also are more likely than whites to exhibit so-called Schneiderian first-rank symptoms of schizophrenia,¹⁵ including:

• delusions of thought broadcasting or insertion
• auditory hallucinations of voices conversing about the patient in the third person.

These symptoms were once used to diagnose schizophrenia, but their lack of specificity has been well documented.^2,16 First-rank symptoms of schizophrenia depend on the specific form of the hallucination or delusion, are likely to be influenced by a patient’s culture, and may be misleading in multicultural populations. Though first-rank symptoms now occupy a minor role in U.S. diagnostic systems, they might continue to sway clinicians—even when using structured diagnostic interviews—to inappropriately diagnose schizophrenia in lieu of affective disorders in minority patients.¹⁵

To extend this finding, our group¹⁶ studied rates and severity of affective and psychotic symptoms—particularly first-rank symptoms—in 100 patients with psychotic mania who met DSM-III-R criteria for bipolar disorder (80%) or schizoaffective disorder, bipolar type (20%) as determined by structured diagnostic interview. No differences in affective symptoms between African-American and white patients were seen. African-Americans were more likely to endorse auditory hallucinations and to report severe auditory hallucinations of voices commenting on their behavior—the only first-rank symptom on which they differed from whites.

Though their affective symptoms were similar, African-Americans were significantly more likely than whites to have been diagnosed with a schizophrenia-spectrum disorder. Because misdiagnosis of African-Americans could not be explained by psychotic symptoms—which were as severe as those of white patients—these findings suggest other mechanisms were at work.

UNIDENTIFIED AFFECTIVE SYMPTOMS

Underidentification of mood disorders in African-American patients may also lead to over-diagnosis of schizophrenia. In a sample of 99 patients, colleagues and I¹⁷ compared clinical diagnoses made in a psychiatric emergency service with those by research investigators using a structured clinical interview. Reasons for diagnostic differences were identified and divided into two categories:

• the same symptoms were recorded but applied differently to diagnostic criteria (criterion variance)
• different information was recorded, which led to diagnostic discrepancies (information variance).

Differences occurred significantly more often in African-American than in white patients, but only information variance was associated with ethnicity. This suggests that clinicians are less likely to elicit appropriate information from African-American than from white psychiatric patients. The fact that researchers obtained this information during diagnostic interviews suggests that the patients could provide it when given appropriate prompts. Specifically, affective symptoms were less likely to be elicited by clinicians than by researchers.

PATIENT WARINESS

Minority patients, when interacting with clinicians of the majority population, may project “protective wariness.”¹⁸ Specific behaviors include hesitancy or reluctance to fully engage with the care provider as a precaution against being exploited or harmed. Cultural misunderstandings¹⁹ and patient concerns about past reports of minorities receiving substandard or unethical health care²⁰ may contribute to this behavior.

Whaley²¹ compared nonpathologic distrust and paranoia in 404 community-living African-Americans and whites. Some were healthy, and some had diagnoses of schizophrenia or depression. African-Americans—particularly those with psychiatric disorders—showed higher levels of distrust than whites. Distrust was also associated with depression in African-Americans but not in whites. Whaley concluded that:

• depressed African-Americans may exhibit more distrust toward clinicians than do whites
• this distrust puts African-Americans at risk of being perceived as paranoid and being misdiagnosed with paranoid schizophrenia.

Table

Remedial actions to avoid ethnic bias in diagnosing schizophrenia

Though Whaley did not report differences in distrust between African-American men and women, others have noted that distrust of health providers may be more common in minority men.¹⁸

RACIAL STEREOTYPING

Compared with similar white men, African-American men with mental disorders are more likely to be:

• referred for mental health care through social and legal—rather than medical—systems and to be involuntarily committed
• perceived as violent—even though controlled research suggests they are not. This misperception can lead to excessive medication and restraints.²²

Differential treatment of African-American men may create a cycle of distrust, hostility, and additional inappropriate treatment. Together, these factors may increase the risk that African-American men will be misdiagnosed with schizophrenia.

Past racism in biomedical and psychiatric practice and research has been documented^23,24 and more recently reviewed by Lawson.¹⁹ Historically, African-Americans were perceived to have a “primitive psychic” nature that was thought to be more susceptible to schizophrenia than depression.¹⁹ Whether these or similar racist stereotypes continue to inject ethnic bias into clinical assessment requires further study.

WHERE DO WE GO FROM HERE?

Although research into methods to eliminate ethnicity bias is sparse, the work reviewed in this article suggests ways that psychiatrists can minimize this problem (Table).

Obtain comprehensive information. Use structured interviews, such as the Structured Clinical Interview for DSM-IV (SCID), and rating scales, such as the Hamilton Depression Scale, which require clinicians to ask about all types of symptoms, particularly affective symptoms.

Review treatment records. Review your practice patterns for evidence of schizophrenia over-diagnosis in African-Americans or other ethnic groups. Examine ethnic differences in legal referrals or use of restraints or seclusion, which may indicate an ethnic bias in how threats are perceived. Only by being aware of bias can one correct it.

Become familiar with cultural and ethnic differences in idioms of distress. Specifically, review research in cultural psychiatry to identify potential differences among cultural groups in how they describe psychiatric symptoms. Talk with colleagues or friends from other cultural groups, and read literature from different ethnic perspectives to increase your cultural sensitivity.

Consult with psychiatrists with expertise in cultural variability of clinical presentation when the diagnosis or threat assessment seems unclear. Consultation is recommended if a patient’s diagnosis is uncertain or if you detect bias in your practice.

These interventions require clinicians to become familiar with psychosocial differences in how patients of various cultural and ethnic groups express psychiatric symptoms. With this understanding, we can better engage wary patients, obtain valid information, and improve clinical practice and patient outcomes.

Finally, psychiatry’s diagnostic systems need to continually address how patient assessment is influenced by ethnicity, culture, gender, and other socio-demographic factors. Studies are needed to examine the contributions of multiple factors—such as symptom differences and stereotyping—that contribute to ethnic-related diagnostic disparities.

Related resources

• Paul AM. Painting insanity black: Why are there more black schizophrenics? Salon.com Dec. 1, 1999. http://www.salon.com/books/it/1999/12/01/schizo/index.html
• Alarcon RD, Westermeyer J, Foulks EF, Ruiz P. Clinical relevance of contemporary cultural psychiatry. J Nerv Ment Dis 1999;187: 465-71.
• Williams DR, Neighbors HW, Jackson JS. Racial/ethnic discrimination and health: findings from community studies. Am J Public Health 2003;93:200-8.
• Lin KM, Smith MW, Ortiz V. Culture and psychopharmacology. Psychiatr Clin North Am 2001; 24:523-38.

Acknowledgement

Preparation of this manuscript was supported in part by National Institutes of Health grant MH56352.

In patients with psychotic symptoms, why are African-Americans more likely than whites to be diagnosed with schizophrenia? After more than 30 years of debate, some answers—and remedies for the problem—are becoming clear.

In psychiatry, where interpersonal interactions are key to eliciting diagnostic symptoms and signs, there is an intrinsic risk of misinterpretation when clinician and patient are of different cultural, ethnic, or socioeconomic backgrounds. This article analyzes four factors that contribute to misinterpretation and to ethnic misdiagnosis of schizophrenia. Culturally sensitive strategies are offered to avoid diagnostic bias in clinical practice.

SCHIZOPHRENIA MISDIAGNOSIS

Large epidemiologic studies report similar rates of schizophrenia and bipolar disorder in African-American and white populations.¹ Although patients of both races have been wrongly diagnosed with schizophrenia, the pattern is stronger and more persistent in African-Americans.

Box 1

In the 1970s, Simon et al² studied 192 hospitalized patients, of whom all African-Americans and 85% of whites had been identified clinically as having schizophrenia. Using a structured interview, the researchers found that only 40% of the African Americans and 50% of the whites met diagnostic criteria for schizophrenia. African-Americans with mood disorders were found to be at particular risk of schizophrenia misdiagnosis.

In the 1980s, among 76 patients with a clinical diagnosis of schizophrenia, Mukherjee et al³ diagnosed one-half (52%) with bipolar disorder using a structured clinical interview. Schizophrenia misdiagnoses were more common in African-Americans (86%) and Hispanics (83%) than in whites (51%). In particular, African-Americans were most likely to be misdiagnosed with paranoid schizophrenia. African-Americans complained more commonly than whites of auditory hallucinations, which may represent an ethnic difference in symptomatic presentation of psychotic mood disorders.

In the 1990s, colleagues and I conducted two studies—one of 173 patients in a Tennessee psychiatric hospital⁴ and the other of 490 patients in an Ohio psychiatric emergency service⁵—and found yet again that African-Americans were more likely than whites to be diagnosed with schizophrenia. In the hospital study, higher rates of schizophrenia diagnosis were associated with lower rates of mood disorder diagnosis. This inverse relationship implied that African-Americans with mood disorders were being misdiagnosed with schizophrenia.

Men were more likely than women to be diagnosed with schizophrenia, suggesting that African-American men were most likely to be misdiagnosed. When adjustments were made for gender, black women were found to be at higher risk for misdiagnosis than white women.

Lawson et al⁶ extended this research in a population-based study of African-Americans living in Tennessee. They found that African-Americans constituted 16% of the state’s population but 48% of psychiatric inpatients diagnosed with schizophrenia and 37% of psychiatric outpatients.

CONSEQUENCES OF INACCURATE DIAGNOSIS

Differentiating between schizophrenia (Box 1) and a psychotic mood disorder (Box 2) is more than a semantic exercise. Schizophrenia implies a chronic, unremitting, debilitating illness that worsens over time. Though this perception of schizophrenia is not entirely accurate, in clinical practice its diagnosis imparts a bleak prognosis that may lower the clinician’s expectations for the patient.⁷

Schizophrenia misdiagnosis also may lead the psychiatrist to rely excessively on antipsychotics, rather than attempting thymoleptic and psychotherapy trials. Studies suggest that African-American patients are more likely than similar white patients to receive antipsychotics^4,8,9 and less likely to receive psychotherapy.^5,10

Reasons why African-Americans are often misdiagnosed with schizophrenia remain unclear but probably include four contributing factors:

• differences in symptom presentation compared with whites
• failure by clinicians to identify affective symptoms in African-Americans
• minority patients’ wariness when dealing with health services
• and racial stereotyping.

DIFFERENCES IN SYMPTOM EXPRESSION

African-American patients with mood disorders or schizophrenia are more likely than are similar white patients to complain of auditory hallucinations.^11-13 For example, Strakowski et al¹⁴ examined 330 patients with nonaffective and psychotic diagnoses in a study that was used to develop DSM-IV criteria for schizophrenia. Auditory hallucinations were rated as more severe in African-American than in similar white patients.

Box 2

African-American patients also are more likely than whites to exhibit so-called Schneiderian first-rank symptoms of schizophrenia,¹⁵ including:

• delusions of thought broadcasting or insertion
• auditory hallucinations of voices conversing about the patient in the third person.

These symptoms were once used to diagnose schizophrenia, but their lack of specificity has been well documented.^2,16 First-rank symptoms of schizophrenia depend on the specific form of the hallucination or delusion, are likely to be influenced by a patient’s culture, and may be misleading in multicultural populations. Though first-rank symptoms now occupy a minor role in U.S. diagnostic systems, they might continue to sway clinicians—even when using structured diagnostic interviews—to inappropriately diagnose schizophrenia in lieu of affective disorders in minority patients.¹⁵

To extend this finding, our group¹⁶ studied rates and severity of affective and psychotic symptoms—particularly first-rank symptoms—in 100 patients with psychotic mania who met DSM-III-R criteria for bipolar disorder (80%) or schizoaffective disorder, bipolar type (20%) as determined by structured diagnostic interview. No differences in affective symptoms between African-American and white patients were seen. African-Americans were more likely to endorse auditory hallucinations and to report severe auditory hallucinations of voices commenting on their behavior—the only first-rank symptom on which they differed from whites.

Though their affective symptoms were similar, African-Americans were significantly more likely than whites to have been diagnosed with a schizophrenia-spectrum disorder. Because misdiagnosis of African-Americans could not be explained by psychotic symptoms—which were as severe as those of white patients—these findings suggest other mechanisms were at work.

UNIDENTIFIED AFFECTIVE SYMPTOMS

Underidentification of mood disorders in African-American patients may also lead to over-diagnosis of schizophrenia. In a sample of 99 patients, colleagues and I¹⁷ compared clinical diagnoses made in a psychiatric emergency service with those by research investigators using a structured clinical interview. Reasons for diagnostic differences were identified and divided into two categories:

• the same symptoms were recorded but applied differently to diagnostic criteria (criterion variance)
• different information was recorded, which led to diagnostic discrepancies (information variance).

Differences occurred significantly more often in African-American than in white patients, but only information variance was associated with ethnicity. This suggests that clinicians are less likely to elicit appropriate information from African-American than from white psychiatric patients. The fact that researchers obtained this information during diagnostic interviews suggests that the patients could provide it when given appropriate prompts. Specifically, affective symptoms were less likely to be elicited by clinicians than by researchers.

PATIENT WARINESS

Minority patients, when interacting with clinicians of the majority population, may project “protective wariness.”¹⁸ Specific behaviors include hesitancy or reluctance to fully engage with the care provider as a precaution against being exploited or harmed. Cultural misunderstandings¹⁹ and patient concerns about past reports of minorities receiving substandard or unethical health care²⁰ may contribute to this behavior.

Whaley²¹ compared nonpathologic distrust and paranoia in 404 community-living African-Americans and whites. Some were healthy, and some had diagnoses of schizophrenia or depression. African-Americans—particularly those with psychiatric disorders—showed higher levels of distrust than whites. Distrust was also associated with depression in African-Americans but not in whites. Whaley concluded that:

• depressed African-Americans may exhibit more distrust toward clinicians than do whites
• this distrust puts African-Americans at risk of being perceived as paranoid and being misdiagnosed with paranoid schizophrenia.

Table

Remedial actions to avoid ethnic bias in diagnosing schizophrenia

Though Whaley did not report differences in distrust between African-American men and women, others have noted that distrust of health providers may be more common in minority men.¹⁸

RACIAL STEREOTYPING

Compared with similar white men, African-American men with mental disorders are more likely to be:

• referred for mental health care through social and legal—rather than medical—systems and to be involuntarily committed
• perceived as violent—even though controlled research suggests they are not. This misperception can lead to excessive medication and restraints.²²

Differential treatment of African-American men may create a cycle of distrust, hostility, and additional inappropriate treatment. Together, these factors may increase the risk that African-American men will be misdiagnosed with schizophrenia.

Past racism in biomedical and psychiatric practice and research has been documented^23,24 and more recently reviewed by Lawson.¹⁹ Historically, African-Americans were perceived to have a “primitive psychic” nature that was thought to be more susceptible to schizophrenia than depression.¹⁹ Whether these or similar racist stereotypes continue to inject ethnic bias into clinical assessment requires further study.

WHERE DO WE GO FROM HERE?

Although research into methods to eliminate ethnicity bias is sparse, the work reviewed in this article suggests ways that psychiatrists can minimize this problem (Table).

Obtain comprehensive information. Use structured interviews, such as the Structured Clinical Interview for DSM-IV (SCID), and rating scales, such as the Hamilton Depression Scale, which require clinicians to ask about all types of symptoms, particularly affective symptoms.

Review treatment records. Review your practice patterns for evidence of schizophrenia over-diagnosis in African-Americans or other ethnic groups. Examine ethnic differences in legal referrals or use of restraints or seclusion, which may indicate an ethnic bias in how threats are perceived. Only by being aware of bias can one correct it.

Become familiar with cultural and ethnic differences in idioms of distress. Specifically, review research in cultural psychiatry to identify potential differences among cultural groups in how they describe psychiatric symptoms. Talk with colleagues or friends from other cultural groups, and read literature from different ethnic perspectives to increase your cultural sensitivity.

Consult with psychiatrists with expertise in cultural variability of clinical presentation when the diagnosis or threat assessment seems unclear. Consultation is recommended if a patient’s diagnosis is uncertain or if you detect bias in your practice.

These interventions require clinicians to become familiar with psychosocial differences in how patients of various cultural and ethnic groups express psychiatric symptoms. With this understanding, we can better engage wary patients, obtain valid information, and improve clinical practice and patient outcomes.

Finally, psychiatry’s diagnostic systems need to continually address how patient assessment is influenced by ethnicity, culture, gender, and other socio-demographic factors. Studies are needed to examine the contributions of multiple factors—such as symptom differences and stereotyping—that contribute to ethnic-related diagnostic disparities.

Related resources

• Paul AM. Painting insanity black: Why are there more black schizophrenics? Salon.com Dec. 1, 1999. http://www.salon.com/books/it/1999/12/01/schizo/index.html
• Alarcon RD, Westermeyer J, Foulks EF, Ruiz P. Clinical relevance of contemporary cultural psychiatry. J Nerv Ment Dis 1999;187: 465-71.
• Williams DR, Neighbors HW, Jackson JS. Racial/ethnic discrimination and health: findings from community studies. Am J Public Health 2003;93:200-8.
• Lin KM, Smith MW, Ortiz V. Culture and psychopharmacology. Psychiatr Clin North Am 2001; 24:523-38.

Acknowledgement

Preparation of this manuscript was supported in part by National Institutes of Health grant MH56352.