Current Psychiatry

Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.

HOW IT WORKS

Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.¹ The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.

Table 1

Acamprosate: Fast facts

The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).

Table 2

Acamprosate’s proposed mechanisms of action*

PHARMACOKINETICS

Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.²

Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.

Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.

The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.

Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.³ How acamprosate interacts with renally excreted drugs such as lithium is unknown.

In two studies following 24 healthy volunteers⁴ and 23 alcohol-dependent patients,⁵ concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.

EFFICACY

Acamprosate with psychosocial treatment increased total abstinent days in:

• 15 randomized, controlled trials (RCT) conducted in Europe⁶
• a meta-analysis of 12 methodologically comparable RCTs conducted in Europe⁷
• an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.²

Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.⁷ Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.² Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.

Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.^3,6,7

In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.

In one 12-week RCT,⁸ naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.

The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,⁹ funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.

SAFETY

Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance

The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.¹⁰ For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.

Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.

TOLERABILITY

Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.⁷

GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.⁷ Diarrhea may be transient and may also resolve with a reduced dosage.⁶

Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.

Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.⁹

CLINICAL IMPLICATIONS

Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.

Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.

Related resources

• Campral Web site. www.campral.com
• National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
• National Institute on Drug Abuse. www.nida.nih.gov

Drug brand names

• Acamprosate • Campral
• Disulfiram • Antabuse
• Naltrexone • ReVia

Disclosure

Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.

Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.

HOW IT WORKS

Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.¹ The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.

Table 1

Acamprosate: Fast facts

The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).

Table 2

Acamprosate’s proposed mechanisms of action*

PHARMACOKINETICS

Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.²

Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.

Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.

The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.

Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.³ How acamprosate interacts with renally excreted drugs such as lithium is unknown.

In two studies following 24 healthy volunteers⁴ and 23 alcohol-dependent patients,⁵ concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.

EFFICACY

Acamprosate with psychosocial treatment increased total abstinent days in:

• 15 randomized, controlled trials (RCT) conducted in Europe⁶
• a meta-analysis of 12 methodologically comparable RCTs conducted in Europe⁷
• an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.²

Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.⁷ Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.² Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.

Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.^3,6,7

In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.

In one 12-week RCT,⁸ naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.

The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,⁹ funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.

SAFETY

Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance

The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.¹⁰ For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.

Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.

TOLERABILITY

Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.⁷

GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.⁷ Diarrhea may be transient and may also resolve with a reduced dosage.⁶

Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.

Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.⁹

CLINICAL IMPLICATIONS

Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.

Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.

Related resources

• Campral Web site. www.campral.com
• National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
• National Institute on Drug Abuse. www.nida.nih.gov

Drug brand names

• Acamprosate • Campral
• Disulfiram • Antabuse
• Naltrexone • ReVia

Disclosure

Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.

Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.

HOW IT WORKS

Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.¹ The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.

Table 1

Acamprosate: Fast facts

The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).

Table 2

Acamprosate’s proposed mechanisms of action*

PHARMACOKINETICS

Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.²

Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.

Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.

The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.

Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.³ How acamprosate interacts with renally excreted drugs such as lithium is unknown.

In two studies following 24 healthy volunteers⁴ and 23 alcohol-dependent patients,⁵ concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.

EFFICACY

Acamprosate with psychosocial treatment increased total abstinent days in:

• 15 randomized, controlled trials (RCT) conducted in Europe⁶
• a meta-analysis of 12 methodologically comparable RCTs conducted in Europe⁷
• an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.²

Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.⁷ Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.² Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.

Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.^3,6,7

In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.

In one 12-week RCT,⁸ naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.

The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,⁹ funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.

SAFETY

Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance

The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.¹⁰ For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.

Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.

TOLERABILITY

Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.⁷

GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.⁷ Diarrhea may be transient and may also resolve with a reduced dosage.⁶

Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.

Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.⁹

CLINICAL IMPLICATIONS

Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.

Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.

Related resources

• Campral Web site. www.campral.com
• National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
• National Institute on Drug Abuse. www.nida.nih.gov

Drug brand names

• Acamprosate • Campral
• Disulfiram • Antabuse
• Naltrexone • ReVia

Disclosure

Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.

Nonbenzodiazepine hypnotics have become mainstays in insomnia treatment. These agents do not interfere with cognitive function upon awakening, compared with benzodiazepines and other agents used off-label as hypnotics.¹

Eszopiclone has shown efficacy in clinical trials for treating short-term and long-term (lasting ≥3 weeks) insomnia. By contrast, zaleplon and zolpidem are indicated for short-term insomnia treatment.

HOW IT WORKS

Eszopiclone, a cyclopyrrolone, is the racemic form of zopiclone, an agent used worldwide to treat insomnia but not available in the United States. The racemic zopiclone has a high affinity for benzodiazepine binding sites in the cerebral cortex, hippocampus, and cerebellum.

As with the selective benzodiazepine receptor agonists zaleplon and zolpidem, information on eszopiclone’s receptor binding profile is limited. It is unclear if the agent binds directly to the benzodiazepine receptor or to a related site on the GABA receptor complex.

Table

Eszopiclone: Fast facts

PHARMACOKINETICS

Preliminary studies suggest eszopiclone is rapidly absorbed from the GI tract, mostly within 1 hour of taking it.^2,3 The agent reaches peak concentration within 30 minutes to 4 hours in healthy persons. A high-fat or heavy meal may delay hypnotic onset by approximately 1 hour.

Eszopiclone is metabolized mostly through the 3A4 isoenzyme of the cytochrome P(CYP)-450 system, although the CYP 2E1 isoenzyme also plays a minor role. About 75% of the dose is excreted in urine.⁴ Because its elimination half-life is approximately 6 hours, eszopiclone leaves no residual effects when patients awaken after about 6 hours of sleep.¹

Because they take weeks to eliminate, some older sleep-promoting medications can cause increasing daytime sedation when used daily. By contrast, eszopiclone can be taken once daily with no risk of drug accumulation.

EFFICACY

Although relatively few clinical studies of eszopiclone have been published, the new-drug application submitted to the FDA summarized 24 clinical trials totaling more than 2,700 subjects.

Zammit et al⁵ gave 308 patients eszopiclone, 2 or 3 mg HS (at bedtime), or placebo for 6 weeks. Eszopiclone decreased time to falling asleep, increased total sleep time, improved continuity of sleep, and increased overall sleep quality throughout the night. After 6 weeks, patients in the treatment group showed:

• no residual morning sedation based on repeated polysomnography and morning questionnaire measures
• no residual daytime sedation based on results of the Digit Symbol Substitution Test, which gauges psychomotor impairment.

Patients taking 3 mg showed reduced wakefulness at night on objective and subjective measures compared with the placebo group.

A randomized, double-blind, multicenter, placebo-controlled study (N=788)^6,7 assessed eszopiclone’s safety and efficacy across 6 months in patients with chronic insomnia. Before enrollment, patients slept

SAFETY AND TOLERABILITY

Eszopiclone was well tolerated in preclinical and clinical trials. The most common adverse event was a bitter taste reported by 34% of participants; this prompted 1.7% of patients in one study⁴ to discontinue eszopiclone, compared with 0.5% of patients taking placebo. Other common adverse effects included:

• daytime somnolence, (8% prevalence, 2.2% dropout rate
• depression (1% dropout rate).⁴

Krystal et al found no clinically significant changes in vital signs, ECG results, laboratory values, and physical examination findings between the eszopiclone and placebo groups.^6,7

Few significant interactions between eszopiclone and other drugs have been reported. However:

• Increased sedation and decreased psychomotor functioning were observed with eszopiclone, 3 mg, and olanzapine, 10 mg.
• Drugs that inhibit (eg, ketoconazole) or induce (eg, rifampicin) the CYP 3A4 isoenzyme may alter eszopiclone levels.⁸
• A possible drug-drug interaction between eszopiclone and alcohol, 0.7 g/kg, decreased psychomotor performance for up to 4 hours after alcohol use.⁸

No significant drug-drug interactions were reported between eszopiclone and paroxetine or lorazepam.⁴

In another case, the parent compound zopiclone given concomitantly with trimipramine decreased both drugs’ bioavailability but did not noticeably change either drug’s clinical effect.⁹ As eszopiclone and zopiclone are chemically similar, be careful when giving eszopiclone to patients taking trimipramine or similar medications, such as tricyclic antidepressants.

DOSING

Start eszopiclone at 2 mg HS for adults and titrate to 3 mg as needed. For many patients, 3 mg may suffice as maintenance therapy. The risks and benefits of dosing eszopiclone at >3 mg are not known.

Lower doses are recommended for patients age >65 because of the risk of decreased motor and/or cognitive performance. Give 2 mg for maintenance and 1 mg for difficulty falling asleep. There are no other known contraindications to eszopiclone use.

As with other hypnotics, supplement eszopiclone with sleep hygiene education and relaxation techniques.

CLINICAL IMPLICATIONS

Eszopiclone has shown efficacy for >2 weeks in primary insomnia, suggesting the agent may help treat chronic insomnia.

As with other nonbenzodiazepine hypnotics, off-label use of eszopiclone with antidepressants may help treat insomnia secondary to depressive or anxiety disorders. Research is needed to gauge the drug’s effectiveness for this use.

Related resources

• American Academy of Sleep Medicine. www.aasmnet.org
• Lunesta Web site. www.lunesta.com

Drug brand names

• Eszopiclone • Lunesta
• Ketoconazole • Nizoral
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Trimipramine • Surmontil
• Zaleplon • Sonata
• Zolpidem • Ambien

Disclosure

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

Nonbenzodiazepine hypnotics have become mainstays in insomnia treatment. These agents do not interfere with cognitive function upon awakening, compared with benzodiazepines and other agents used off-label as hypnotics.¹

Eszopiclone has shown efficacy in clinical trials for treating short-term and long-term (lasting ≥3 weeks) insomnia. By contrast, zaleplon and zolpidem are indicated for short-term insomnia treatment.

HOW IT WORKS

Eszopiclone, a cyclopyrrolone, is the racemic form of zopiclone, an agent used worldwide to treat insomnia but not available in the United States. The racemic zopiclone has a high affinity for benzodiazepine binding sites in the cerebral cortex, hippocampus, and cerebellum.

As with the selective benzodiazepine receptor agonists zaleplon and zolpidem, information on eszopiclone’s receptor binding profile is limited. It is unclear if the agent binds directly to the benzodiazepine receptor or to a related site on the GABA receptor complex.

Table

Eszopiclone: Fast facts

PHARMACOKINETICS

Preliminary studies suggest eszopiclone is rapidly absorbed from the GI tract, mostly within 1 hour of taking it.^2,3 The agent reaches peak concentration within 30 minutes to 4 hours in healthy persons. A high-fat or heavy meal may delay hypnotic onset by approximately 1 hour.

Eszopiclone is metabolized mostly through the 3A4 isoenzyme of the cytochrome P(CYP)-450 system, although the CYP 2E1 isoenzyme also plays a minor role. About 75% of the dose is excreted in urine.⁴ Because its elimination half-life is approximately 6 hours, eszopiclone leaves no residual effects when patients awaken after about 6 hours of sleep.¹

Because they take weeks to eliminate, some older sleep-promoting medications can cause increasing daytime sedation when used daily. By contrast, eszopiclone can be taken once daily with no risk of drug accumulation.

EFFICACY

Although relatively few clinical studies of eszopiclone have been published, the new-drug application submitted to the FDA summarized 24 clinical trials totaling more than 2,700 subjects.

Zammit et al⁵ gave 308 patients eszopiclone, 2 or 3 mg HS (at bedtime), or placebo for 6 weeks. Eszopiclone decreased time to falling asleep, increased total sleep time, improved continuity of sleep, and increased overall sleep quality throughout the night. After 6 weeks, patients in the treatment group showed:

• no residual morning sedation based on repeated polysomnography and morning questionnaire measures
• no residual daytime sedation based on results of the Digit Symbol Substitution Test, which gauges psychomotor impairment.

Patients taking 3 mg showed reduced wakefulness at night on objective and subjective measures compared with the placebo group.

A randomized, double-blind, multicenter, placebo-controlled study (N=788)^6,7 assessed eszopiclone’s safety and efficacy across 6 months in patients with chronic insomnia. Before enrollment, patients slept

SAFETY AND TOLERABILITY

Eszopiclone was well tolerated in preclinical and clinical trials. The most common adverse event was a bitter taste reported by 34% of participants; this prompted 1.7% of patients in one study⁴ to discontinue eszopiclone, compared with 0.5% of patients taking placebo. Other common adverse effects included:

• daytime somnolence, (8% prevalence, 2.2% dropout rate
• depression (1% dropout rate).⁴

Krystal et al found no clinically significant changes in vital signs, ECG results, laboratory values, and physical examination findings between the eszopiclone and placebo groups.^6,7

Few significant interactions between eszopiclone and other drugs have been reported. However:

• Increased sedation and decreased psychomotor functioning were observed with eszopiclone, 3 mg, and olanzapine, 10 mg.
• Drugs that inhibit (eg, ketoconazole) or induce (eg, rifampicin) the CYP 3A4 isoenzyme may alter eszopiclone levels.⁸
• A possible drug-drug interaction between eszopiclone and alcohol, 0.7 g/kg, decreased psychomotor performance for up to 4 hours after alcohol use.⁸

No significant drug-drug interactions were reported between eszopiclone and paroxetine or lorazepam.⁴

In another case, the parent compound zopiclone given concomitantly with trimipramine decreased both drugs’ bioavailability but did not noticeably change either drug’s clinical effect.⁹ As eszopiclone and zopiclone are chemically similar, be careful when giving eszopiclone to patients taking trimipramine or similar medications, such as tricyclic antidepressants.

DOSING

Start eszopiclone at 2 mg HS for adults and titrate to 3 mg as needed. For many patients, 3 mg may suffice as maintenance therapy. The risks and benefits of dosing eszopiclone at >3 mg are not known.

Lower doses are recommended for patients age >65 because of the risk of decreased motor and/or cognitive performance. Give 2 mg for maintenance and 1 mg for difficulty falling asleep. There are no other known contraindications to eszopiclone use.

As with other hypnotics, supplement eszopiclone with sleep hygiene education and relaxation techniques.

CLINICAL IMPLICATIONS

Eszopiclone has shown efficacy for >2 weeks in primary insomnia, suggesting the agent may help treat chronic insomnia.

As with other nonbenzodiazepine hypnotics, off-label use of eszopiclone with antidepressants may help treat insomnia secondary to depressive or anxiety disorders. Research is needed to gauge the drug’s effectiveness for this use.

Related resources

• American Academy of Sleep Medicine. www.aasmnet.org
• Lunesta Web site. www.lunesta.com

Drug brand names

• Eszopiclone • Lunesta
• Ketoconazole • Nizoral
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Trimipramine • Surmontil
• Zaleplon • Sonata
• Zolpidem • Ambien

Disclosure

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

Nonbenzodiazepine hypnotics have become mainstays in insomnia treatment. These agents do not interfere with cognitive function upon awakening, compared with benzodiazepines and other agents used off-label as hypnotics.¹

Eszopiclone has shown efficacy in clinical trials for treating short-term and long-term (lasting ≥3 weeks) insomnia. By contrast, zaleplon and zolpidem are indicated for short-term insomnia treatment.

HOW IT WORKS

Eszopiclone, a cyclopyrrolone, is the racemic form of zopiclone, an agent used worldwide to treat insomnia but not available in the United States. The racemic zopiclone has a high affinity for benzodiazepine binding sites in the cerebral cortex, hippocampus, and cerebellum.

As with the selective benzodiazepine receptor agonists zaleplon and zolpidem, information on eszopiclone’s receptor binding profile is limited. It is unclear if the agent binds directly to the benzodiazepine receptor or to a related site on the GABA receptor complex.

Table

Eszopiclone: Fast facts

PHARMACOKINETICS

Preliminary studies suggest eszopiclone is rapidly absorbed from the GI tract, mostly within 1 hour of taking it.^2,3 The agent reaches peak concentration within 30 minutes to 4 hours in healthy persons. A high-fat or heavy meal may delay hypnotic onset by approximately 1 hour.

Eszopiclone is metabolized mostly through the 3A4 isoenzyme of the cytochrome P(CYP)-450 system, although the CYP 2E1 isoenzyme also plays a minor role. About 75% of the dose is excreted in urine.⁴ Because its elimination half-life is approximately 6 hours, eszopiclone leaves no residual effects when patients awaken after about 6 hours of sleep.¹

Because they take weeks to eliminate, some older sleep-promoting medications can cause increasing daytime sedation when used daily. By contrast, eszopiclone can be taken once daily with no risk of drug accumulation.

EFFICACY

Although relatively few clinical studies of eszopiclone have been published, the new-drug application submitted to the FDA summarized 24 clinical trials totaling more than 2,700 subjects.

Zammit et al⁵ gave 308 patients eszopiclone, 2 or 3 mg HS (at bedtime), or placebo for 6 weeks. Eszopiclone decreased time to falling asleep, increased total sleep time, improved continuity of sleep, and increased overall sleep quality throughout the night. After 6 weeks, patients in the treatment group showed:

• no residual morning sedation based on repeated polysomnography and morning questionnaire measures
• no residual daytime sedation based on results of the Digit Symbol Substitution Test, which gauges psychomotor impairment.

Patients taking 3 mg showed reduced wakefulness at night on objective and subjective measures compared with the placebo group.

A randomized, double-blind, multicenter, placebo-controlled study (N=788)^6,7 assessed eszopiclone’s safety and efficacy across 6 months in patients with chronic insomnia. Before enrollment, patients slept

SAFETY AND TOLERABILITY

Eszopiclone was well tolerated in preclinical and clinical trials. The most common adverse event was a bitter taste reported by 34% of participants; this prompted 1.7% of patients in one study⁴ to discontinue eszopiclone, compared with 0.5% of patients taking placebo. Other common adverse effects included:

• daytime somnolence, (8% prevalence, 2.2% dropout rate
• depression (1% dropout rate).⁴

Krystal et al found no clinically significant changes in vital signs, ECG results, laboratory values, and physical examination findings between the eszopiclone and placebo groups.^6,7

Few significant interactions between eszopiclone and other drugs have been reported. However:

• Increased sedation and decreased psychomotor functioning were observed with eszopiclone, 3 mg, and olanzapine, 10 mg.
• Drugs that inhibit (eg, ketoconazole) or induce (eg, rifampicin) the CYP 3A4 isoenzyme may alter eszopiclone levels.⁸
• A possible drug-drug interaction between eszopiclone and alcohol, 0.7 g/kg, decreased psychomotor performance for up to 4 hours after alcohol use.⁸

No significant drug-drug interactions were reported between eszopiclone and paroxetine or lorazepam.⁴

In another case, the parent compound zopiclone given concomitantly with trimipramine decreased both drugs’ bioavailability but did not noticeably change either drug’s clinical effect.⁹ As eszopiclone and zopiclone are chemically similar, be careful when giving eszopiclone to patients taking trimipramine or similar medications, such as tricyclic antidepressants.

DOSING

Start eszopiclone at 2 mg HS for adults and titrate to 3 mg as needed. For many patients, 3 mg may suffice as maintenance therapy. The risks and benefits of dosing eszopiclone at >3 mg are not known.

Lower doses are recommended for patients age >65 because of the risk of decreased motor and/or cognitive performance. Give 2 mg for maintenance and 1 mg for difficulty falling asleep. There are no other known contraindications to eszopiclone use.

As with other hypnotics, supplement eszopiclone with sleep hygiene education and relaxation techniques.

CLINICAL IMPLICATIONS

Eszopiclone has shown efficacy for >2 weeks in primary insomnia, suggesting the agent may help treat chronic insomnia.

As with other nonbenzodiazepine hypnotics, off-label use of eszopiclone with antidepressants may help treat insomnia secondary to depressive or anxiety disorders. Research is needed to gauge the drug’s effectiveness for this use.

Related resources

• American Academy of Sleep Medicine. www.aasmnet.org
• Lunesta Web site. www.lunesta.com

Drug brand names

• Eszopiclone • Lunesta
• Ketoconazole • Nizoral
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Trimipramine • Surmontil
• Zaleplon • Sonata
• Zolpidem • Ambien

Disclosure

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

Presentation: Strange change

Mr. A, age 66, has lived an active life but now just sits around most of the day. Once an early riser, he is sleeping until 11 AM or noon daily. His wife frequently must motivate him to get out of bed.

Mr. A’s wife describes him as good-natured and extroverted, but she says lately he has also become increasingly withdrawn and quiet. People often think he is angry with them.

His dining habits also have changed. He used to wait until everyone had been served before beginning his meal, but he now starts eating immediately. He often overeats and has gained 15 pounds over 1 year.

Mr. A has always driven manual-transmission vehicles but has trouble remembering how to shift gears on his new car. While visiting his daughter, he could not operate the bathroom faucets properly and scalded himself. His daughter also noticed he does not wash his hands before eating or after toileting.

Findings. Mr. A presents to our clinic at his wife’s and daughter’s insistence but says his memory is fine and he can perform all activities of daily living (ADL). He denies depressive, anxiety, or psychotic symptoms but has hypertension and probable benign prostatic hypertrophy. He is taking ramipril, 5 mg/d for hypertension, donepezil, 10 mg/d for cognitive deficits, and aspirin, 325 mg/d to prevent a heart attack. Physical exam shows no gross neurologic abnormalities. Organ systems are normal.

Mr. A’s Folstein Mini-Mental State Exam (MMSE) score (22/30) indicates cognitive impairment. During his mental status exam, he is pleasant, cooperative, and makes good eye contact. He answers appropriately, but his speech lacks spontaneity. He smiles throughout the interview, even while discussing serious questions regarding his health. He is fully oriented but lacks insight into his deficits.

Brain MRI, ordered after he had presented to another hospital with similar complaints, is normal. PET scan shows frontal lobe hypometabolism, right greater than left, and mild underperfusion of the right basal ganglia and right temporal lobe.

Table 1

Frontotemporal dementia subtypes and their clinical features

The authors’ observations

Mr. A’s clinical course suggests frontotemporal dementia (FTD), a spectrum of non-Alzheimer’s dementias characterized by focal atrophy of the brain’s frontal and anterior temporal regions (Table 1). These dementias loosely share clinicopathologic features, including:

• decline in social interpersonal conduct
  
• emotional blunting
  
• loss of insight
  
• disinhibition.¹
  

FTD is the second most-common cause of dementia after AD in the years preceding old age but remains underdiagnosed. Onset is most common between ages 45 to 65 but can occur before age 30 and in the elderly.

FTD’s clinical presentation usually reflects distribution of pathologic changes rather than a precise histologic subtype. Major clinical presentations include a frontal or behavioral variant (frontal variant FTD associated with corticobasal degeneration or motor neuron disease), a progressive fluent aphasia (temporal lobe variant FTD), and a progressive nonfluent aphasia. Mr. A’s lack of initiative, emotional reactivity, and loss of social graces with normal speech pattern suggest frontal variant FTD.

Behavioral changes associated with FTD include:

• Decline in social conduct, including tactlessness and breaches of etiquette, associated with predominantly right-hemisphere pathology.³
  
• Apathy, which correlates with severity of medial frontal-anterior cingulate involvement.
  
• Dietary changes—typically overeating (hyperorality) with a preference for sweets.⁴
  

Cognitive changes in FTD—attentional deficits, poor abstraction, difficulty shifting mental set, and perseverative tendencies—point to frontal lobe involvement.³

Neurologic signs usually are absent early in the disease, although patients may display primitive reflexes. As FTD progresses, patients may develop parkinsonian signs of akinesia and rigidity, which can be marked. Some develop neurologic signs consistent with motor neuron disease.³

Differential diagnosis. FTD is most often mistaken for AD. In one study, FTD was found at autopsy in 18 of 21 patients who had been diagnosed with AD.⁵ Cerebrovascular dementia, Huntington’s disease, Lewy body dementia, and Creutzfeldt-Jakob disease are other differential diagnoses.

Suspect FTD if behavioral symptoms become more prominent than cognitive decline. In one study,⁶ patients with FTD exhibited:

• early loss of social awareness
  
• early loss of personal awareness
  
• progressive loss of speech
  
• stereotyped and perseverative behaviors
  
• and/or hyperorality.
  

The authors’ observations

Clinical evaluation for FTD should include a neuropsychiatric assessment, neuropsychological testing, and neuroimaging.

Neuropsychiatric assessment. Unlike AD, cholinergic acetyltransferase and acetylcholinesterase activity is well-preserved in FTD. Serotonergic disturbances are more common in FTD than in AD and are linked to impulsivity, irritability, and changes in affect and eating behavior.

On neuropsychological testing, memory is relatively intact. Orientation and recall of recent personal events is good, but anterograde memory test performance is variable. Patients with FTD often do poorly on recall-based tasks. Spontaneous conversation is often reduced, but patients perform well on semantic-based tasks and visuospatial tests when organizational aspects are minimized.

The MMSE is unreliable for detecting and monitoring patients with FTD. For example, some who require nursing home care have normal MMSE scores.⁴ Frontal executive tasks—such as the Wisconsin Card Sorting Test, Stroop Test, and verbal fluency examinations—can uncover dorsolateral dysfunction. Quantifiable decision-making and risk-taking exercises can reveal orbitobasal dysfunction.⁴

Neuroimaging. MRI shows left temporal lobe atrophy in patients with primary progressive aphasia; both frontal lobes are atrophic in frontal variant FTD. By contrast, the mesial temporal lobes are atrophic in AD.⁷ Frontal and anterior temporal lobe atrophy become more apparent in the latter stages of frontal variant FTD.⁴

Single-photon emission computed tomography (SPECT) using technetium and hexylmethylpropylene amineoxine can detect ventromedial frontal hypoperfusion before atrophy is evident. Order SPECT when the diagnosis is uncertain or the presentation or disease course is unusual.

Treatment: Taking aim at apathy

Donepezil, 10 mg/d, was continued to address Mr. A’s cognitive decline. Bupropion, 100 mg/d, was added to deal with his apathy and low energy. We saw him every 4 months.

Table 2

Medications shown beneficial for treating FTD

On follow-up, Mr. A’s gait is slower, and he has “shakiness” and mild finger clumsiness. Physical exam shows no problems and he is fully oriented, but his MMSE score (17/30) indicates further cognitive loss and he still lacks insight into his condition. Neuropsychological tests reveal:

• marked delays in processing and acting on information
  
• diminished working memory
  
• trouble understanding spatial functions
  
• decreased speech
  
• moderate to severe executive function impairments
  
• severe impairments in fine-motor dexterity, receptive and expressive language, and verbal and visual memory.
  

Bupropion alleviated Mr. A’s apathy at first, but an increase to 200 mg/d led to tremors and disrupted sleep. Bupropion was decreased to 150 mg/d; we would add a selective serotonin reuptake inhibitor (SSRI) if apathy persisted. We advised his wife and daughter to take him to adult day care and to make sure he does not drive. Follow-up interval is reduced to 2 months.

Eight weeks later, Mr. A is confused and anxious and his affect is remarkably flat, but he behaves appropriately in day care. We stopped bupropion because it did not resolve his apathy.

The authors’ observations

Treat apathy, avolition, anhedonia, social withdrawal, irritability, and/or inappropriate behaviors if these symptoms compromise quality of life for the patient and caregiver. Also try to preserve cognitive function.

Few large-scale clinical trials have addressed FTD pharmacotherapy (Table 2). In an open-label trial, 11 patients with FTD took sertraline, 50 to 125 mg/d, paroxetine, 20 mg/d, or fluoxetine, 20 mg/d. After 3 months, no one’s symptoms worsened and nine patients (82%) had reduced disinhibition, depressive symptoms, carbohydrate craving, and/or compulsions.⁵

In another open-label, uncontrolled trial, behavioral symptoms improved in eight patients with FTD who took paroxetine, up to 20 mg/d for 14 months. Baseline global performance, cognition, and planning scores remained stable, but attention and abstract reasoning were decreased. Side effects were tolerable.⁸

In a 12-week crossover study, 26 patients with FTD received placebo or trazodone, 150 or 300 mg/d depending on dose tolerability. Irritability, agitation, depressive symptoms, and/or eating disorders improved significantly in 10 patients, and behavioral disturbances decreased >25% in 16 patients. Trazodone also was well tolerated.⁹

Dopamine use in FTD can contribute to behavioral dysregulation. D₂ blockers occasionally are used to manage behavioral disturbances, but selective dopamine agonists might be more beneficial. Recent studies suggest that bromocriptine, a D₁ and D₂ dopaminergic agonist, may improve select frontal features and perseveration in dementia.¹⁰

In one case report, quantitative EEG correlated with SPECT showed that methylphenidate, dose unknown, helped improve behavior and normalize profoundly imbalanced bifrontotemporal slowing.¹¹

Recommendation. Try sertraline, 50 to 125 mg/d, or fluoxetine, 20 mg/d, to address behavioral symptoms. Paroxetine is another option, but use it cautiously as its anticholinergic properties could cause confusion in older patients. If the patient does not respond to the SSRI after 6 to 8 weeks, try trazodone, 150 to 300 mg/d.

Conclusion: The 15-month mark

We started citalopram, 20 mg/d, to treat Mr. A’s apathy and anxiety; and memantine, 5 mg/d titrated to 10 mg bid, to try to slow his cognitive and functional decline. Donepezil, 10 mg/d, was continued.

We encouraged Mr. A’s wife and daughter to take him to adult day care as often as possible. Mr. A also was placed on a waiting list for a skilled nursing facility.

Mr. A continued to worsen. Fifteen months after initial presentation, he is incontinent of urine and feces and needs help performing most basic ADLs. He continues to overeat and has gained 6.3 pounds over 4 months. His MMSE score (12/30) indicates severe cognitive impairment.

The authors’ observations

Many patients with FTD eventually need long-term placement, a change in environment marked by unfamiliar faces and disrupted routines. Patients often react by becoming disorganized, irritable, and agitated.

No standard method exists to structure this transition for FTD patients. In rare cases, patients have been transferred to secure units for medication management until stabilized.¹²

Help calm the patient’s fears by describing the typical nursing home and the range of services it offers. Arrange a meeting with the patient, primary care physician, and the nursing home’s intake coordinator to review available services. Make sure the patient and caregiver receive brochures and other literature about the facility.

Related resources

• Association for Frontotemporal Dementias. www.ftd-picks.org.
  
• National Institute of Neurological Disorders and Stroke. Pick’s Disease Information Page. Available at: www.ninds.nih.gov/disorders/picks/picks.htm. Accessed Jan. 11, 2005.
  
• Family Caregiver Alliance. Frontotemporal Dementia. Available at: www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=573&expandnodeid=384. Accessed Jan. 11, 2005.
  

• Bromocriptine • Parlodel
  
• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Donepezil • Aricept
  
• Fluoxetine • Prozac
  
• Memantine • Namenda
  
• Methylphenidate • Concerta, Ritalin
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  

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

Acknowledgment

This project is supported by the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant 1 K01 HP 00071-01 and Geriatric Academic Career Award. The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the BPHr, HRSA, DHHS or the U.S. Government.”

Presentation: Strange change

Mr. A, age 66, has lived an active life but now just sits around most of the day. Once an early riser, he is sleeping until 11 AM or noon daily. His wife frequently must motivate him to get out of bed.

Mr. A’s wife describes him as good-natured and extroverted, but she says lately he has also become increasingly withdrawn and quiet. People often think he is angry with them.

His dining habits also have changed. He used to wait until everyone had been served before beginning his meal, but he now starts eating immediately. He often overeats and has gained 15 pounds over 1 year.

Mr. A has always driven manual-transmission vehicles but has trouble remembering how to shift gears on his new car. While visiting his daughter, he could not operate the bathroom faucets properly and scalded himself. His daughter also noticed he does not wash his hands before eating or after toileting.

Findings. Mr. A presents to our clinic at his wife’s and daughter’s insistence but says his memory is fine and he can perform all activities of daily living (ADL). He denies depressive, anxiety, or psychotic symptoms but has hypertension and probable benign prostatic hypertrophy. He is taking ramipril, 5 mg/d for hypertension, donepezil, 10 mg/d for cognitive deficits, and aspirin, 325 mg/d to prevent a heart attack. Physical exam shows no gross neurologic abnormalities. Organ systems are normal.

Mr. A’s Folstein Mini-Mental State Exam (MMSE) score (22/30) indicates cognitive impairment. During his mental status exam, he is pleasant, cooperative, and makes good eye contact. He answers appropriately, but his speech lacks spontaneity. He smiles throughout the interview, even while discussing serious questions regarding his health. He is fully oriented but lacks insight into his deficits.

Brain MRI, ordered after he had presented to another hospital with similar complaints, is normal. PET scan shows frontal lobe hypometabolism, right greater than left, and mild underperfusion of the right basal ganglia and right temporal lobe.

Table 1

Frontotemporal dementia subtypes and their clinical features

The authors’ observations

Mr. A’s clinical course suggests frontotemporal dementia (FTD), a spectrum of non-Alzheimer’s dementias characterized by focal atrophy of the brain’s frontal and anterior temporal regions (Table 1). These dementias loosely share clinicopathologic features, including:

• decline in social interpersonal conduct
  
• emotional blunting
  
• loss of insight
  
• disinhibition.¹
  

FTD is the second most-common cause of dementia after AD in the years preceding old age but remains underdiagnosed. Onset is most common between ages 45 to 65 but can occur before age 30 and in the elderly.

FTD’s clinical presentation usually reflects distribution of pathologic changes rather than a precise histologic subtype. Major clinical presentations include a frontal or behavioral variant (frontal variant FTD associated with corticobasal degeneration or motor neuron disease), a progressive fluent aphasia (temporal lobe variant FTD), and a progressive nonfluent aphasia. Mr. A’s lack of initiative, emotional reactivity, and loss of social graces with normal speech pattern suggest frontal variant FTD.

Behavioral changes associated with FTD include:

• Decline in social conduct, including tactlessness and breaches of etiquette, associated with predominantly right-hemisphere pathology.³
  
• Apathy, which correlates with severity of medial frontal-anterior cingulate involvement.
  
• Dietary changes—typically overeating (hyperorality) with a preference for sweets.⁴
  

Cognitive changes in FTD—attentional deficits, poor abstraction, difficulty shifting mental set, and perseverative tendencies—point to frontal lobe involvement.³

Neurologic signs usually are absent early in the disease, although patients may display primitive reflexes. As FTD progresses, patients may develop parkinsonian signs of akinesia and rigidity, which can be marked. Some develop neurologic signs consistent with motor neuron disease.³

Differential diagnosis. FTD is most often mistaken for AD. In one study, FTD was found at autopsy in 18 of 21 patients who had been diagnosed with AD.⁵ Cerebrovascular dementia, Huntington’s disease, Lewy body dementia, and Creutzfeldt-Jakob disease are other differential diagnoses.

Suspect FTD if behavioral symptoms become more prominent than cognitive decline. In one study,⁶ patients with FTD exhibited:

• early loss of social awareness
  
• early loss of personal awareness
  
• progressive loss of speech
  
• stereotyped and perseverative behaviors
  
• and/or hyperorality.
  

The authors’ observations

Clinical evaluation for FTD should include a neuropsychiatric assessment, neuropsychological testing, and neuroimaging.

Neuropsychiatric assessment. Unlike AD, cholinergic acetyltransferase and acetylcholinesterase activity is well-preserved in FTD. Serotonergic disturbances are more common in FTD than in AD and are linked to impulsivity, irritability, and changes in affect and eating behavior.

On neuropsychological testing, memory is relatively intact. Orientation and recall of recent personal events is good, but anterograde memory test performance is variable. Patients with FTD often do poorly on recall-based tasks. Spontaneous conversation is often reduced, but patients perform well on semantic-based tasks and visuospatial tests when organizational aspects are minimized.

The MMSE is unreliable for detecting and monitoring patients with FTD. For example, some who require nursing home care have normal MMSE scores.⁴ Frontal executive tasks—such as the Wisconsin Card Sorting Test, Stroop Test, and verbal fluency examinations—can uncover dorsolateral dysfunction. Quantifiable decision-making and risk-taking exercises can reveal orbitobasal dysfunction.⁴

Neuroimaging. MRI shows left temporal lobe atrophy in patients with primary progressive aphasia; both frontal lobes are atrophic in frontal variant FTD. By contrast, the mesial temporal lobes are atrophic in AD.⁷ Frontal and anterior temporal lobe atrophy become more apparent in the latter stages of frontal variant FTD.⁴

Single-photon emission computed tomography (SPECT) using technetium and hexylmethylpropylene amineoxine can detect ventromedial frontal hypoperfusion before atrophy is evident. Order SPECT when the diagnosis is uncertain or the presentation or disease course is unusual.

Treatment: Taking aim at apathy

Donepezil, 10 mg/d, was continued to address Mr. A’s cognitive decline. Bupropion, 100 mg/d, was added to deal with his apathy and low energy. We saw him every 4 months.

Table 2

Medications shown beneficial for treating FTD

On follow-up, Mr. A’s gait is slower, and he has “shakiness” and mild finger clumsiness. Physical exam shows no problems and he is fully oriented, but his MMSE score (17/30) indicates further cognitive loss and he still lacks insight into his condition. Neuropsychological tests reveal:

• marked delays in processing and acting on information
  
• diminished working memory
  
• trouble understanding spatial functions
  
• decreased speech
  
• moderate to severe executive function impairments
  
• severe impairments in fine-motor dexterity, receptive and expressive language, and verbal and visual memory.
  

Bupropion alleviated Mr. A’s apathy at first, but an increase to 200 mg/d led to tremors and disrupted sleep. Bupropion was decreased to 150 mg/d; we would add a selective serotonin reuptake inhibitor (SSRI) if apathy persisted. We advised his wife and daughter to take him to adult day care and to make sure he does not drive. Follow-up interval is reduced to 2 months.

Eight weeks later, Mr. A is confused and anxious and his affect is remarkably flat, but he behaves appropriately in day care. We stopped bupropion because it did not resolve his apathy.

The authors’ observations

Treat apathy, avolition, anhedonia, social withdrawal, irritability, and/or inappropriate behaviors if these symptoms compromise quality of life for the patient and caregiver. Also try to preserve cognitive function.

Few large-scale clinical trials have addressed FTD pharmacotherapy (Table 2). In an open-label trial, 11 patients with FTD took sertraline, 50 to 125 mg/d, paroxetine, 20 mg/d, or fluoxetine, 20 mg/d. After 3 months, no one’s symptoms worsened and nine patients (82%) had reduced disinhibition, depressive symptoms, carbohydrate craving, and/or compulsions.⁵

In another open-label, uncontrolled trial, behavioral symptoms improved in eight patients with FTD who took paroxetine, up to 20 mg/d for 14 months. Baseline global performance, cognition, and planning scores remained stable, but attention and abstract reasoning were decreased. Side effects were tolerable.⁸

In a 12-week crossover study, 26 patients with FTD received placebo or trazodone, 150 or 300 mg/d depending on dose tolerability. Irritability, agitation, depressive symptoms, and/or eating disorders improved significantly in 10 patients, and behavioral disturbances decreased >25% in 16 patients. Trazodone also was well tolerated.⁹

Dopamine use in FTD can contribute to behavioral dysregulation. D₂ blockers occasionally are used to manage behavioral disturbances, but selective dopamine agonists might be more beneficial. Recent studies suggest that bromocriptine, a D₁ and D₂ dopaminergic agonist, may improve select frontal features and perseveration in dementia.¹⁰

In one case report, quantitative EEG correlated with SPECT showed that methylphenidate, dose unknown, helped improve behavior and normalize profoundly imbalanced bifrontotemporal slowing.¹¹

Recommendation. Try sertraline, 50 to 125 mg/d, or fluoxetine, 20 mg/d, to address behavioral symptoms. Paroxetine is another option, but use it cautiously as its anticholinergic properties could cause confusion in older patients. If the patient does not respond to the SSRI after 6 to 8 weeks, try trazodone, 150 to 300 mg/d.

Conclusion: The 15-month mark

We started citalopram, 20 mg/d, to treat Mr. A’s apathy and anxiety; and memantine, 5 mg/d titrated to 10 mg bid, to try to slow his cognitive and functional decline. Donepezil, 10 mg/d, was continued.

We encouraged Mr. A’s wife and daughter to take him to adult day care as often as possible. Mr. A also was placed on a waiting list for a skilled nursing facility.

Mr. A continued to worsen. Fifteen months after initial presentation, he is incontinent of urine and feces and needs help performing most basic ADLs. He continues to overeat and has gained 6.3 pounds over 4 months. His MMSE score (12/30) indicates severe cognitive impairment.

The authors’ observations

Many patients with FTD eventually need long-term placement, a change in environment marked by unfamiliar faces and disrupted routines. Patients often react by becoming disorganized, irritable, and agitated.

No standard method exists to structure this transition for FTD patients. In rare cases, patients have been transferred to secure units for medication management until stabilized.¹²

Help calm the patient’s fears by describing the typical nursing home and the range of services it offers. Arrange a meeting with the patient, primary care physician, and the nursing home’s intake coordinator to review available services. Make sure the patient and caregiver receive brochures and other literature about the facility.

Related resources

• Association for Frontotemporal Dementias. www.ftd-picks.org.
  
• National Institute of Neurological Disorders and Stroke. Pick’s Disease Information Page. Available at: www.ninds.nih.gov/disorders/picks/picks.htm. Accessed Jan. 11, 2005.
  
• Family Caregiver Alliance. Frontotemporal Dementia. Available at: www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=573&expandnodeid=384. Accessed Jan. 11, 2005.
  

• Bromocriptine • Parlodel
  
• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Donepezil • Aricept
  
• Fluoxetine • Prozac
  
• Memantine • Namenda
  
• Methylphenidate • Concerta, Ritalin
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  

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

Acknowledgment

This project is supported by the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant 1 K01 HP 00071-01 and Geriatric Academic Career Award. The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the BPHr, HRSA, DHHS or the U.S. Government.”

Presentation: Strange change

Mr. A, age 66, has lived an active life but now just sits around most of the day. Once an early riser, he is sleeping until 11 AM or noon daily. His wife frequently must motivate him to get out of bed.

Mr. A’s wife describes him as good-natured and extroverted, but she says lately he has also become increasingly withdrawn and quiet. People often think he is angry with them.

His dining habits also have changed. He used to wait until everyone had been served before beginning his meal, but he now starts eating immediately. He often overeats and has gained 15 pounds over 1 year.

Mr. A has always driven manual-transmission vehicles but has trouble remembering how to shift gears on his new car. While visiting his daughter, he could not operate the bathroom faucets properly and scalded himself. His daughter also noticed he does not wash his hands before eating or after toileting.

Findings. Mr. A presents to our clinic at his wife’s and daughter’s insistence but says his memory is fine and he can perform all activities of daily living (ADL). He denies depressive, anxiety, or psychotic symptoms but has hypertension and probable benign prostatic hypertrophy. He is taking ramipril, 5 mg/d for hypertension, donepezil, 10 mg/d for cognitive deficits, and aspirin, 325 mg/d to prevent a heart attack. Physical exam shows no gross neurologic abnormalities. Organ systems are normal.

Mr. A’s Folstein Mini-Mental State Exam (MMSE) score (22/30) indicates cognitive impairment. During his mental status exam, he is pleasant, cooperative, and makes good eye contact. He answers appropriately, but his speech lacks spontaneity. He smiles throughout the interview, even while discussing serious questions regarding his health. He is fully oriented but lacks insight into his deficits.

Brain MRI, ordered after he had presented to another hospital with similar complaints, is normal. PET scan shows frontal lobe hypometabolism, right greater than left, and mild underperfusion of the right basal ganglia and right temporal lobe.

Table 1

Frontotemporal dementia subtypes and their clinical features

The authors’ observations

Mr. A’s clinical course suggests frontotemporal dementia (FTD), a spectrum of non-Alzheimer’s dementias characterized by focal atrophy of the brain’s frontal and anterior temporal regions (Table 1). These dementias loosely share clinicopathologic features, including:

• decline in social interpersonal conduct
  
• emotional blunting
  
• loss of insight
  
• disinhibition.¹
  

FTD is the second most-common cause of dementia after AD in the years preceding old age but remains underdiagnosed. Onset is most common between ages 45 to 65 but can occur before age 30 and in the elderly.

FTD’s clinical presentation usually reflects distribution of pathologic changes rather than a precise histologic subtype. Major clinical presentations include a frontal or behavioral variant (frontal variant FTD associated with corticobasal degeneration or motor neuron disease), a progressive fluent aphasia (temporal lobe variant FTD), and a progressive nonfluent aphasia. Mr. A’s lack of initiative, emotional reactivity, and loss of social graces with normal speech pattern suggest frontal variant FTD.

Behavioral changes associated with FTD include:

• Decline in social conduct, including tactlessness and breaches of etiquette, associated with predominantly right-hemisphere pathology.³
  
• Apathy, which correlates with severity of medial frontal-anterior cingulate involvement.
  
• Dietary changes—typically overeating (hyperorality) with a preference for sweets.⁴
  

Cognitive changes in FTD—attentional deficits, poor abstraction, difficulty shifting mental set, and perseverative tendencies—point to frontal lobe involvement.³

Neurologic signs usually are absent early in the disease, although patients may display primitive reflexes. As FTD progresses, patients may develop parkinsonian signs of akinesia and rigidity, which can be marked. Some develop neurologic signs consistent with motor neuron disease.³

Differential diagnosis. FTD is most often mistaken for AD. In one study, FTD was found at autopsy in 18 of 21 patients who had been diagnosed with AD.⁵ Cerebrovascular dementia, Huntington’s disease, Lewy body dementia, and Creutzfeldt-Jakob disease are other differential diagnoses.

Suspect FTD if behavioral symptoms become more prominent than cognitive decline. In one study,⁶ patients with FTD exhibited:

• early loss of social awareness
  
• early loss of personal awareness
  
• progressive loss of speech
  
• stereotyped and perseverative behaviors
  
• and/or hyperorality.
  

The authors’ observations

Clinical evaluation for FTD should include a neuropsychiatric assessment, neuropsychological testing, and neuroimaging.

Neuropsychiatric assessment. Unlike AD, cholinergic acetyltransferase and acetylcholinesterase activity is well-preserved in FTD. Serotonergic disturbances are more common in FTD than in AD and are linked to impulsivity, irritability, and changes in affect and eating behavior.

On neuropsychological testing, memory is relatively intact. Orientation and recall of recent personal events is good, but anterograde memory test performance is variable. Patients with FTD often do poorly on recall-based tasks. Spontaneous conversation is often reduced, but patients perform well on semantic-based tasks and visuospatial tests when organizational aspects are minimized.

The MMSE is unreliable for detecting and monitoring patients with FTD. For example, some who require nursing home care have normal MMSE scores.⁴ Frontal executive tasks—such as the Wisconsin Card Sorting Test, Stroop Test, and verbal fluency examinations—can uncover dorsolateral dysfunction. Quantifiable decision-making and risk-taking exercises can reveal orbitobasal dysfunction.⁴

Neuroimaging. MRI shows left temporal lobe atrophy in patients with primary progressive aphasia; both frontal lobes are atrophic in frontal variant FTD. By contrast, the mesial temporal lobes are atrophic in AD.⁷ Frontal and anterior temporal lobe atrophy become more apparent in the latter stages of frontal variant FTD.⁴

Single-photon emission computed tomography (SPECT) using technetium and hexylmethylpropylene amineoxine can detect ventromedial frontal hypoperfusion before atrophy is evident. Order SPECT when the diagnosis is uncertain or the presentation or disease course is unusual.

Treatment: Taking aim at apathy

Donepezil, 10 mg/d, was continued to address Mr. A’s cognitive decline. Bupropion, 100 mg/d, was added to deal with his apathy and low energy. We saw him every 4 months.

Table 2

Medications shown beneficial for treating FTD

On follow-up, Mr. A’s gait is slower, and he has “shakiness” and mild finger clumsiness. Physical exam shows no problems and he is fully oriented, but his MMSE score (17/30) indicates further cognitive loss and he still lacks insight into his condition. Neuropsychological tests reveal:

• marked delays in processing and acting on information
  
• diminished working memory
  
• trouble understanding spatial functions
  
• decreased speech
  
• moderate to severe executive function impairments
  
• severe impairments in fine-motor dexterity, receptive and expressive language, and verbal and visual memory.
  

Bupropion alleviated Mr. A’s apathy at first, but an increase to 200 mg/d led to tremors and disrupted sleep. Bupropion was decreased to 150 mg/d; we would add a selective serotonin reuptake inhibitor (SSRI) if apathy persisted. We advised his wife and daughter to take him to adult day care and to make sure he does not drive. Follow-up interval is reduced to 2 months.

Eight weeks later, Mr. A is confused and anxious and his affect is remarkably flat, but he behaves appropriately in day care. We stopped bupropion because it did not resolve his apathy.

The authors’ observations

Treat apathy, avolition, anhedonia, social withdrawal, irritability, and/or inappropriate behaviors if these symptoms compromise quality of life for the patient and caregiver. Also try to preserve cognitive function.

Few large-scale clinical trials have addressed FTD pharmacotherapy (Table 2). In an open-label trial, 11 patients with FTD took sertraline, 50 to 125 mg/d, paroxetine, 20 mg/d, or fluoxetine, 20 mg/d. After 3 months, no one’s symptoms worsened and nine patients (82%) had reduced disinhibition, depressive symptoms, carbohydrate craving, and/or compulsions.⁵

In another open-label, uncontrolled trial, behavioral symptoms improved in eight patients with FTD who took paroxetine, up to 20 mg/d for 14 months. Baseline global performance, cognition, and planning scores remained stable, but attention and abstract reasoning were decreased. Side effects were tolerable.⁸

In a 12-week crossover study, 26 patients with FTD received placebo or trazodone, 150 or 300 mg/d depending on dose tolerability. Irritability, agitation, depressive symptoms, and/or eating disorders improved significantly in 10 patients, and behavioral disturbances decreased >25% in 16 patients. Trazodone also was well tolerated.⁹

Dopamine use in FTD can contribute to behavioral dysregulation. D₂ blockers occasionally are used to manage behavioral disturbances, but selective dopamine agonists might be more beneficial. Recent studies suggest that bromocriptine, a D₁ and D₂ dopaminergic agonist, may improve select frontal features and perseveration in dementia.¹⁰

In one case report, quantitative EEG correlated with SPECT showed that methylphenidate, dose unknown, helped improve behavior and normalize profoundly imbalanced bifrontotemporal slowing.¹¹

Recommendation. Try sertraline, 50 to 125 mg/d, or fluoxetine, 20 mg/d, to address behavioral symptoms. Paroxetine is another option, but use it cautiously as its anticholinergic properties could cause confusion in older patients. If the patient does not respond to the SSRI after 6 to 8 weeks, try trazodone, 150 to 300 mg/d.

Conclusion: The 15-month mark

We started citalopram, 20 mg/d, to treat Mr. A’s apathy and anxiety; and memantine, 5 mg/d titrated to 10 mg bid, to try to slow his cognitive and functional decline. Donepezil, 10 mg/d, was continued.

We encouraged Mr. A’s wife and daughter to take him to adult day care as often as possible. Mr. A also was placed on a waiting list for a skilled nursing facility.

Mr. A continued to worsen. Fifteen months after initial presentation, he is incontinent of urine and feces and needs help performing most basic ADLs. He continues to overeat and has gained 6.3 pounds over 4 months. His MMSE score (12/30) indicates severe cognitive impairment.

The authors’ observations

Many patients with FTD eventually need long-term placement, a change in environment marked by unfamiliar faces and disrupted routines. Patients often react by becoming disorganized, irritable, and agitated.

No standard method exists to structure this transition for FTD patients. In rare cases, patients have been transferred to secure units for medication management until stabilized.¹²

Help calm the patient’s fears by describing the typical nursing home and the range of services it offers. Arrange a meeting with the patient, primary care physician, and the nursing home’s intake coordinator to review available services. Make sure the patient and caregiver receive brochures and other literature about the facility.

Related resources

• Association for Frontotemporal Dementias. www.ftd-picks.org.
  
• National Institute of Neurological Disorders and Stroke. Pick’s Disease Information Page. Available at: www.ninds.nih.gov/disorders/picks/picks.htm. Accessed Jan. 11, 2005.
  
• Family Caregiver Alliance. Frontotemporal Dementia. Available at: www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=573&expandnodeid=384. Accessed Jan. 11, 2005.
  

• Bromocriptine • Parlodel
  
• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Donepezil • Aricept
  
• Fluoxetine • Prozac
  
• Memantine • Namenda
  
• Methylphenidate • Concerta, Ritalin
  
• Paroxetine • Paxil
  
• Sertraline • Zoloft
  
• Trazodone • Desyrel
  

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

Acknowledgment

This project is supported by the Division of State, Community, and Public Health, Bureau of Health Professions (BHPr), Health Resources and Services Administration (HSRA), Department of Health and Human Services (DHHS) under grant 1 K01 HP 00071-01 and Geriatric Academic Career Award. The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the BPHr, HRSA, DHHS or the U.S. Government.”

A treatment-resistant patient’s medication history alone may not explain why trial after trial has failed. To help such patients, also evaluate their psychotherapy histories.

CASE: TWO DECADES OF DEPRESSION

Mrs. H, age 48, had battled depression for more than 20 years and had tried numerous antidepressants, including several tricyclics and one monoamine oxidase inhibitor. She was not working and resisted social interaction because of a persistent belief that she was inferior.

When Mrs. H consulted with me, she was seeing a psychiatrist once a month for medication management. She was taking fluoxetine, 80 mg/d, and methylphenidate, 10 mg tid, but remained hopeless and demoralized.

While taking her history, I learned that Mrs. H had been a successful art historian. She seemed surprised when I asked about this; she said her previous psychiatrist had never asked about her work.

I also learned that Mrs. H was relatively euthymic for nearly 7 years in her early 30s. During that time she married, found a challenging job, and received therapy from a psychologist who “really listened and took me seriously.”

I recommended weekly psychotherapy and medication management, both of which I would perform. The first sessions were rocky as several medication augmentation strategies led to side effects and little else. Finally, I left her medications alone and listened to her story.

After 2 years of psychotherapy, Mrs. H is optimistic despite multiple stressors. She is an involved wife and mother, works at a respected academic institution, and has a growing network of friends.

Four history lessons

My experience with Mrs. H and other patients taught me four key lessons about evaluating psychiatric treatment histories:

• Ask about all past and current therapy contacts. Get details on each type of therapy performed, frequency and duration, and patient response to the therapist and therapy.
  
• Look for clues that suggest the patient is open to psychotherapy. Does the patient seem interested in his/her inner life? Does he/she show insight into his/her role in certain situations, especially those involving interpersonal interactions? Can he/she process analogy or metaphor?¹
  
• Don’t be afraid to try psychotherapy with a medication-resistant patient. A round of intensive psychotherapy may calm residual depression or anxiety symptoms.
  
• When possible, perform the psychotherapy yourself to become more familiar with your patients—especially if you are prescribing medication.
  

A treatment-resistant patient’s medication history alone may not explain why trial after trial has failed. To help such patients, also evaluate their psychotherapy histories.

CASE: TWO DECADES OF DEPRESSION

Mrs. H, age 48, had battled depression for more than 20 years and had tried numerous antidepressants, including several tricyclics and one monoamine oxidase inhibitor. She was not working and resisted social interaction because of a persistent belief that she was inferior.

When Mrs. H consulted with me, she was seeing a psychiatrist once a month for medication management. She was taking fluoxetine, 80 mg/d, and methylphenidate, 10 mg tid, but remained hopeless and demoralized.

While taking her history, I learned that Mrs. H had been a successful art historian. She seemed surprised when I asked about this; she said her previous psychiatrist had never asked about her work.

I also learned that Mrs. H was relatively euthymic for nearly 7 years in her early 30s. During that time she married, found a challenging job, and received therapy from a psychologist who “really listened and took me seriously.”

I recommended weekly psychotherapy and medication management, both of which I would perform. The first sessions were rocky as several medication augmentation strategies led to side effects and little else. Finally, I left her medications alone and listened to her story.

After 2 years of psychotherapy, Mrs. H is optimistic despite multiple stressors. She is an involved wife and mother, works at a respected academic institution, and has a growing network of friends.

Four history lessons

My experience with Mrs. H and other patients taught me four key lessons about evaluating psychiatric treatment histories:

• Ask about all past and current therapy contacts. Get details on each type of therapy performed, frequency and duration, and patient response to the therapist and therapy.
  
• Look for clues that suggest the patient is open to psychotherapy. Does the patient seem interested in his/her inner life? Does he/she show insight into his/her role in certain situations, especially those involving interpersonal interactions? Can he/she process analogy or metaphor?¹
  
• Don’t be afraid to try psychotherapy with a medication-resistant patient. A round of intensive psychotherapy may calm residual depression or anxiety symptoms.
  
• When possible, perform the psychotherapy yourself to become more familiar with your patients—especially if you are prescribing medication.
  

A treatment-resistant patient’s medication history alone may not explain why trial after trial has failed. To help such patients, also evaluate their psychotherapy histories.

CASE: TWO DECADES OF DEPRESSION

Mrs. H, age 48, had battled depression for more than 20 years and had tried numerous antidepressants, including several tricyclics and one monoamine oxidase inhibitor. She was not working and resisted social interaction because of a persistent belief that she was inferior.

When Mrs. H consulted with me, she was seeing a psychiatrist once a month for medication management. She was taking fluoxetine, 80 mg/d, and methylphenidate, 10 mg tid, but remained hopeless and demoralized.

While taking her history, I learned that Mrs. H had been a successful art historian. She seemed surprised when I asked about this; she said her previous psychiatrist had never asked about her work.

I also learned that Mrs. H was relatively euthymic for nearly 7 years in her early 30s. During that time she married, found a challenging job, and received therapy from a psychologist who “really listened and took me seriously.”

I recommended weekly psychotherapy and medication management, both of which I would perform. The first sessions were rocky as several medication augmentation strategies led to side effects and little else. Finally, I left her medications alone and listened to her story.

After 2 years of psychotherapy, Mrs. H is optimistic despite multiple stressors. She is an involved wife and mother, works at a respected academic institution, and has a growing network of friends.

Four history lessons

My experience with Mrs. H and other patients taught me four key lessons about evaluating psychiatric treatment histories:

• Ask about all past and current therapy contacts. Get details on each type of therapy performed, frequency and duration, and patient response to the therapist and therapy.
  
• Look for clues that suggest the patient is open to psychotherapy. Does the patient seem interested in his/her inner life? Does he/she show insight into his/her role in certain situations, especially those involving interpersonal interactions? Can he/she process analogy or metaphor?¹
  
• Don’t be afraid to try psychotherapy with a medication-resistant patient. A round of intensive psychotherapy may calm residual depression or anxiety symptoms.
  
• When possible, perform the psychotherapy yourself to become more familiar with your patients—especially if you are prescribing medication.
  

A side from posing a psychiatric emergency, agitation can also signal a potentially serious medical problem (Box). After the patient’s behavior is stabilized, a medical evaluation may be necessary. The letters that spell “agitation” remind us to watch for these problems:

Alcohol dependence, intoxication, or withdrawal can lead to agitation even when obvious signs or symptoms of alcohol use are not present.¹ Watch for nausea, vomiting, tremors, sweating, auditory or visual hallucinations, headaches, and abnormal vital signs. Also watch for confusion, which may precede delirium.

Genetics. Agitation is a presenting symptom in several congenital diseases, such as Huntington’s disease.² Look for Huntington’s chorea, psychotic symptoms, and family history of a congenital disease associated with agitation.

Infections. Agitation in patients with systemic, local, or CNS infections may be seen as psychogenic, thereby delaying medical evaluation.³ Watch for abnormal vital signs, especially fever or sweating. General achiness could signal meningitis, a viral infection prodrome, or tetanus infection.

Tumors. Patients with primary cancer with CNS metastasis or primary CNS tumors may present with agitation but no other symptoms or signs of cancer.⁴ Find out if the patient has a personal or family history of cancer. Watch for unexplained pain that cannot be adequately controlled.

Akathisia. Inner psychological restlessness and observable movements associated with akathisia can manifest as agitation.⁵ Ask whether the patient is using illicit drugs or medications (eg, some antipsychotics) that may cause akathisia.

Trauma. Agitated patients with brain injuries caused by surgery, burns, or heatstroke usually present with obvious clinical signs. However, persons with asymptomatic, undiagnosed bone and skull fractures may also become agitated.⁶ Elderly and frail persons and patients with a past head injury also are at risk for trauma-related agitation.

Box

Illicit drugs. Agitation may point to drug intoxication, addiction, or withdrawal. Do a urine and blood screen to check for use of stimulants, anabolic steroids, ketamine, phencyclidine (PCP), or “club drugs” such as methylenedioxymethamphetamine (MDMA, or Ecstasy) and gamma hydroxybutyrate (GHB).⁷

Other predisposing medical factors for agitation include chronic pain, respiratory distress, and endocrine and metabolic abnormalities.^1,2,7,8 Refer the patient for a medical workup, including laboratory and diagnostic tests based on lab results.

Neuropsychiatric conditions. Agitation may be the main presenting symptom of seizures, as well as:

• degenerative CNS diseases such as Parkinson’s disease, multiple sclerosis, and dementias, especially the Alzheimer’s type
  
• Tourette syndrome
  
• a pervasive developmental disorder
  
• inherited movement disorders, such as Wilson’s disease or Hallervorden-Spatz syndrome.^2,8-10
  

Get a detailed patient and family history, then refer the patient for comprehensive physical and neurologic examinations.

Acknowledgments

The authors thank Leonard D. Williams, PA, and Drs. Nestor Manzano, Craig Campbell, Scott Ahles, Robert Hierholzer, and Avak Howsepian for their help.

A side from posing a psychiatric emergency, agitation can also signal a potentially serious medical problem (Box). After the patient’s behavior is stabilized, a medical evaluation may be necessary. The letters that spell “agitation” remind us to watch for these problems:

Alcohol dependence, intoxication, or withdrawal can lead to agitation even when obvious signs or symptoms of alcohol use are not present.¹ Watch for nausea, vomiting, tremors, sweating, auditory or visual hallucinations, headaches, and abnormal vital signs. Also watch for confusion, which may precede delirium.

Genetics. Agitation is a presenting symptom in several congenital diseases, such as Huntington’s disease.² Look for Huntington’s chorea, psychotic symptoms, and family history of a congenital disease associated with agitation.

Infections. Agitation in patients with systemic, local, or CNS infections may be seen as psychogenic, thereby delaying medical evaluation.³ Watch for abnormal vital signs, especially fever or sweating. General achiness could signal meningitis, a viral infection prodrome, or tetanus infection.

Tumors. Patients with primary cancer with CNS metastasis or primary CNS tumors may present with agitation but no other symptoms or signs of cancer.⁴ Find out if the patient has a personal or family history of cancer. Watch for unexplained pain that cannot be adequately controlled.

Akathisia. Inner psychological restlessness and observable movements associated with akathisia can manifest as agitation.⁵ Ask whether the patient is using illicit drugs or medications (eg, some antipsychotics) that may cause akathisia.

Trauma. Agitated patients with brain injuries caused by surgery, burns, or heatstroke usually present with obvious clinical signs. However, persons with asymptomatic, undiagnosed bone and skull fractures may also become agitated.⁶ Elderly and frail persons and patients with a past head injury also are at risk for trauma-related agitation.

Box

Illicit drugs. Agitation may point to drug intoxication, addiction, or withdrawal. Do a urine and blood screen to check for use of stimulants, anabolic steroids, ketamine, phencyclidine (PCP), or “club drugs” such as methylenedioxymethamphetamine (MDMA, or Ecstasy) and gamma hydroxybutyrate (GHB).⁷

Other predisposing medical factors for agitation include chronic pain, respiratory distress, and endocrine and metabolic abnormalities.^1,2,7,8 Refer the patient for a medical workup, including laboratory and diagnostic tests based on lab results.

Neuropsychiatric conditions. Agitation may be the main presenting symptom of seizures, as well as:

• degenerative CNS diseases such as Parkinson’s disease, multiple sclerosis, and dementias, especially the Alzheimer’s type
  
• Tourette syndrome
  
• a pervasive developmental disorder
  
• inherited movement disorders, such as Wilson’s disease or Hallervorden-Spatz syndrome.^2,8-10
  

Get a detailed patient and family history, then refer the patient for comprehensive physical and neurologic examinations.

Acknowledgments

The authors thank Leonard D. Williams, PA, and Drs. Nestor Manzano, Craig Campbell, Scott Ahles, Robert Hierholzer, and Avak Howsepian for their help.

A side from posing a psychiatric emergency, agitation can also signal a potentially serious medical problem (Box). After the patient’s behavior is stabilized, a medical evaluation may be necessary. The letters that spell “agitation” remind us to watch for these problems:

Alcohol dependence, intoxication, or withdrawal can lead to agitation even when obvious signs or symptoms of alcohol use are not present.¹ Watch for nausea, vomiting, tremors, sweating, auditory or visual hallucinations, headaches, and abnormal vital signs. Also watch for confusion, which may precede delirium.

Genetics. Agitation is a presenting symptom in several congenital diseases, such as Huntington’s disease.² Look for Huntington’s chorea, psychotic symptoms, and family history of a congenital disease associated with agitation.

Infections. Agitation in patients with systemic, local, or CNS infections may be seen as psychogenic, thereby delaying medical evaluation.³ Watch for abnormal vital signs, especially fever or sweating. General achiness could signal meningitis, a viral infection prodrome, or tetanus infection.

Tumors. Patients with primary cancer with CNS metastasis or primary CNS tumors may present with agitation but no other symptoms or signs of cancer.⁴ Find out if the patient has a personal or family history of cancer. Watch for unexplained pain that cannot be adequately controlled.

Akathisia. Inner psychological restlessness and observable movements associated with akathisia can manifest as agitation.⁵ Ask whether the patient is using illicit drugs or medications (eg, some antipsychotics) that may cause akathisia.

Trauma. Agitated patients with brain injuries caused by surgery, burns, or heatstroke usually present with obvious clinical signs. However, persons with asymptomatic, undiagnosed bone and skull fractures may also become agitated.⁶ Elderly and frail persons and patients with a past head injury also are at risk for trauma-related agitation.

Box

Illicit drugs. Agitation may point to drug intoxication, addiction, or withdrawal. Do a urine and blood screen to check for use of stimulants, anabolic steroids, ketamine, phencyclidine (PCP), or “club drugs” such as methylenedioxymethamphetamine (MDMA, or Ecstasy) and gamma hydroxybutyrate (GHB).⁷

Other predisposing medical factors for agitation include chronic pain, respiratory distress, and endocrine and metabolic abnormalities.^1,2,7,8 Refer the patient for a medical workup, including laboratory and diagnostic tests based on lab results.

Neuropsychiatric conditions. Agitation may be the main presenting symptom of seizures, as well as:

• degenerative CNS diseases such as Parkinson’s disease, multiple sclerosis, and dementias, especially the Alzheimer’s type
  
• Tourette syndrome
  
• a pervasive developmental disorder
  
• inherited movement disorders, such as Wilson’s disease or Hallervorden-Spatz syndrome.^2,8-10
  

Get a detailed patient and family history, then refer the patient for comprehensive physical and neurologic examinations.

Acknowledgments

The authors thank Leonard D. Williams, PA, and Drs. Nestor Manzano, Craig Campbell, Scott Ahles, Robert Hierholzer, and Avak Howsepian for their help.

We agree with Dr. Leslie Citrome that too few randomized trials have been done to conclude that mood stabilizers are effective in schizophrenia (Current Psychiatry, December 2004). We believe, however, that there is enough evidence to support augmenting antipsychotics with mood stabilizers in treatment-resistant cases.

Results from randomized, controlled trials (RCT) are the gold standard of evidence, but methodologic, logistic, and ethical drawbacks often limit RCTs of most drugs. Because mood stabilizer augmentation in schizophrenia is a relatively new strategy, we should not dismiss its use in treatment-resistant cases even if non-RCT evidence supports this use.

Although we often see schizophrenia as a single entity, we are dealing with a group of disorders with heterogeneous causes and variable presentations.¹ Based on our work in forensic and challenging-behavior units in the United States and Europe, adjunctive mood stabilizers are usually targeted toward psychomotor agitation, aggression, and affective instability—often with significant benefit.

When hostility in schizophrenia is targeted, a randomized study has shown the advantages of a divalproex/antipsychotic combination over antipsychotic monotherapy.² Unfortunately, most other evidence supporting mood stabilizer use in schizophrenia is retrospective, open-labeled, and uncontrolled.³

Clinicians should encourage funding for rigorous RCTs of mood stabilizers in schizophrenia. In the interim, clinical judgment should dictate which agents to use and when.

Babatunde Adetunji, MD
Attending psychiatrist
Kirby Forensic Psychiatric Center
New York, NY

Adedapo Williams, MD
Attending psychiatrist
John H. Stroger Jr. Hospital of Cook County
Chicago, IL

Maju Mathews, MD
Psychiatry resident
Drexel University College of Medicine
Philadelphia, PA

Thomas Osinowo, MD
Director of forensic services
Northcoast Behavioral Health Care
Toledo, OH

References

1. Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry (9th ed). Philadelphia: Lippincott Williams and Wilkins, 2003:471.
   
2. Citrome L. Casey DE, Daniel DG, et al. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. Psychiatr Serv 2004;55:290–4.
   
3. Afaq I, Riaz J, Sedky K, et al. Divalproex as a calmative adjunct for aggressive schizophrenic patients. J Ky Med Assoc 2002;100:17–22.
   

We agree with Dr. Leslie Citrome that too few randomized trials have been done to conclude that mood stabilizers are effective in schizophrenia (Current Psychiatry, December 2004). We believe, however, that there is enough evidence to support augmenting antipsychotics with mood stabilizers in treatment-resistant cases.

Results from randomized, controlled trials (RCT) are the gold standard of evidence, but methodologic, logistic, and ethical drawbacks often limit RCTs of most drugs. Because mood stabilizer augmentation in schizophrenia is a relatively new strategy, we should not dismiss its use in treatment-resistant cases even if non-RCT evidence supports this use.

Although we often see schizophrenia as a single entity, we are dealing with a group of disorders with heterogeneous causes and variable presentations.¹ Based on our work in forensic and challenging-behavior units in the United States and Europe, adjunctive mood stabilizers are usually targeted toward psychomotor agitation, aggression, and affective instability—often with significant benefit.

When hostility in schizophrenia is targeted, a randomized study has shown the advantages of a divalproex/antipsychotic combination over antipsychotic monotherapy.² Unfortunately, most other evidence supporting mood stabilizer use in schizophrenia is retrospective, open-labeled, and uncontrolled.³

Clinicians should encourage funding for rigorous RCTs of mood stabilizers in schizophrenia. In the interim, clinical judgment should dictate which agents to use and when.

Babatunde Adetunji, MD
Attending psychiatrist
Kirby Forensic Psychiatric Center
New York, NY

Adedapo Williams, MD
Attending psychiatrist
John H. Stroger Jr. Hospital of Cook County
Chicago, IL

Maju Mathews, MD
Psychiatry resident
Drexel University College of Medicine
Philadelphia, PA

Thomas Osinowo, MD
Director of forensic services
Northcoast Behavioral Health Care
Toledo, OH

References

1. Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry (9th ed). Philadelphia: Lippincott Williams and Wilkins, 2003:471.
   
2. Citrome L. Casey DE, Daniel DG, et al. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. Psychiatr Serv 2004;55:290–4.
   
3. Afaq I, Riaz J, Sedky K, et al. Divalproex as a calmative adjunct for aggressive schizophrenic patients. J Ky Med Assoc 2002;100:17–22.
   

We agree with Dr. Leslie Citrome that too few randomized trials have been done to conclude that mood stabilizers are effective in schizophrenia (Current Psychiatry, December 2004). We believe, however, that there is enough evidence to support augmenting antipsychotics with mood stabilizers in treatment-resistant cases.

Results from randomized, controlled trials (RCT) are the gold standard of evidence, but methodologic, logistic, and ethical drawbacks often limit RCTs of most drugs. Because mood stabilizer augmentation in schizophrenia is a relatively new strategy, we should not dismiss its use in treatment-resistant cases even if non-RCT evidence supports this use.

Although we often see schizophrenia as a single entity, we are dealing with a group of disorders with heterogeneous causes and variable presentations.¹ Based on our work in forensic and challenging-behavior units in the United States and Europe, adjunctive mood stabilizers are usually targeted toward psychomotor agitation, aggression, and affective instability—often with significant benefit.

When hostility in schizophrenia is targeted, a randomized study has shown the advantages of a divalproex/antipsychotic combination over antipsychotic monotherapy.² Unfortunately, most other evidence supporting mood stabilizer use in schizophrenia is retrospective, open-labeled, and uncontrolled.³

Clinicians should encourage funding for rigorous RCTs of mood stabilizers in schizophrenia. In the interim, clinical judgment should dictate which agents to use and when.

Babatunde Adetunji, MD
Attending psychiatrist
Kirby Forensic Psychiatric Center
New York, NY

Adedapo Williams, MD
Attending psychiatrist
John H. Stroger Jr. Hospital of Cook County
Chicago, IL

Maju Mathews, MD
Psychiatry resident
Drexel University College of Medicine
Philadelphia, PA

Thomas Osinowo, MD
Director of forensic services
Northcoast Behavioral Health Care
Toledo, OH

References

1. Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry (9th ed). Philadelphia: Lippincott Williams and Wilkins, 2003:471.
   
2. Citrome L. Casey DE, Daniel DG, et al. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. Psychiatr Serv 2004;55:290–4.
   
3. Afaq I, Riaz J, Sedky K, et al. Divalproex as a calmative adjunct for aggressive schizophrenic patients. J Ky Med Assoc 2002;100:17–22.
   

For some years, I have been considering giving up traditional psychotherapy and concentrating on “rationalization therapy.” Patients will tell me what they want to do, and I will help them rationalize it.

Much of what passes for psychotherapy is, in fact, rationalization therapy in disguise. What’s different about my idea is that accurately labeling this new therapy will make the transaction more honest. We will abandon any talk about “making patients well” and concentrate on making them feel good about getting what they want.

Rationalization therapy can also rescue us from time-based billing. One reason surgeons make more money than we do is that they can bill on codes related to a procedure’s difficulty. We, on the other hand, are trapped into billing for the minutes we spend with a patient, regardless of how difficult our psychotherapeutic goals may be.

For rationalization therapy, I propose that we bill on how difficult it is to rationalize the patient’s wish, regardless of how long it takes us to help him or her rationalize it. For example, rationalizing taking an extra sick day from work when not really sick would be a Level-1 code with low reimbursement. Rationalizing murder would be a Level-3 code, resulting in much higher reimbursement.

For rationalizing murder, we also would be entitled to a higher relative value unit (RVU) reimbursement. This RVU would take into account not just our “physicians work” component but also a cost-of-practice component for higher professional liability costs we might incur.

Rationalization therapy thus would be win-win for us and our patients. My only hesitation in making this practice change has to do with another idea I’m considering, called “procrastination therapy.” But I’ll get to that another day.

For some years, I have been considering giving up traditional psychotherapy and concentrating on “rationalization therapy.” Patients will tell me what they want to do, and I will help them rationalize it.

Much of what passes for psychotherapy is, in fact, rationalization therapy in disguise. What’s different about my idea is that accurately labeling this new therapy will make the transaction more honest. We will abandon any talk about “making patients well” and concentrate on making them feel good about getting what they want.

Rationalization therapy can also rescue us from time-based billing. One reason surgeons make more money than we do is that they can bill on codes related to a procedure’s difficulty. We, on the other hand, are trapped into billing for the minutes we spend with a patient, regardless of how difficult our psychotherapeutic goals may be.

For rationalization therapy, I propose that we bill on how difficult it is to rationalize the patient’s wish, regardless of how long it takes us to help him or her rationalize it. For example, rationalizing taking an extra sick day from work when not really sick would be a Level-1 code with low reimbursement. Rationalizing murder would be a Level-3 code, resulting in much higher reimbursement.

For rationalizing murder, we also would be entitled to a higher relative value unit (RVU) reimbursement. This RVU would take into account not just our “physicians work” component but also a cost-of-practice component for higher professional liability costs we might incur.

Rationalization therapy thus would be win-win for us and our patients. My only hesitation in making this practice change has to do with another idea I’m considering, called “procrastination therapy.” But I’ll get to that another day.

For some years, I have been considering giving up traditional psychotherapy and concentrating on “rationalization therapy.” Patients will tell me what they want to do, and I will help them rationalize it.

Much of what passes for psychotherapy is, in fact, rationalization therapy in disguise. What’s different about my idea is that accurately labeling this new therapy will make the transaction more honest. We will abandon any talk about “making patients well” and concentrate on making them feel good about getting what they want.

Rationalization therapy can also rescue us from time-based billing. One reason surgeons make more money than we do is that they can bill on codes related to a procedure’s difficulty. We, on the other hand, are trapped into billing for the minutes we spend with a patient, regardless of how difficult our psychotherapeutic goals may be.

For rationalization therapy, I propose that we bill on how difficult it is to rationalize the patient’s wish, regardless of how long it takes us to help him or her rationalize it. For example, rationalizing taking an extra sick day from work when not really sick would be a Level-1 code with low reimbursement. Rationalizing murder would be a Level-3 code, resulting in much higher reimbursement.

For rationalizing murder, we also would be entitled to a higher relative value unit (RVU) reimbursement. This RVU would take into account not just our “physicians work” component but also a cost-of-practice component for higher professional liability costs we might incur.

Rationalization therapy thus would be win-win for us and our patients. My only hesitation in making this practice change has to do with another idea I’m considering, called “procrastination therapy.” But I’ll get to that another day.

Progress notes must convey that the psychiatrist provided quality care and respected the patient’s condition and wishes. Knowing what information to include—and what to leave out—can help you and your colleagues avoid a malpractice judgment.

Follow these 10 dos and don’ts of writing progress notes:

1. Be concise. Document all necessary information but avoid extraneous details, such as in this example:

“Patient moved to Kansas at age 4. Her parents separated when she was 6 and they moved back to Chicago, then reunited and moved to Indiana, where father took a job as a shoe salesman. When he lost that job, they moved back to Chicago and divorced for good. Mother remarried a fireman, who was an alcoholic; they stayed together for 2 years until …”

Instead, simply write:

“Patient’s childhood was chaotic with many moves; her mother remarried x 3. No physical or sexual abuse …”

2. Include adequate details. Do not exclude information critical to explaining treatment decisions. Describe the symptoms the patient is reporting and the signs you see—or do not see.

This example offers insufficient detail:

“Patient’s parents told her that they just bought a new car. She recalled the first car they had gotten when she was little, and how that made her happy. She talked about the first car she owned. Plan: Add lithium …”

By contrast, the following example explicitly describes signs and symptoms. Also be sure to include a short explanation when changing, discontinuing, or adding a medication:

“Patient reports her mood is much improved. She cannot recall what made her feel so depressed last week. She is hyperverbal, talking rapidly, gesticulating as she talks—much more animated, as compared to psychomotor-retarded presentation of last week, when SSRI was started. Assess: Bipolar switch. Plan: Add lithium, 300 mg bid, and titrate.”

3. Be careful when describing treatment of a patient who is suicidal at presentation. Your notes must contain clear, well-reasoned explanations for:

• discontinuing suicide precautions
• not hospitalizing outpatients who express suicidal ideation.

If the patient attempts or commits suicide shortly after the visit, your progress note may be your best—and only—defense against a malpractice claim. This example offers no convincing argument that the patient will not attempt suicide:

“Patient reports that he feels better. He denies suicidal ideation. He thinks the antidepressant is working. Nursing notes indicate no problems. He would like to get dressed and take a walk outside …”

Instead, verbatim patient statements offer more-concrete proof that the patient wants to live:

“He said he is his family’s sole support and could never abandon them …”

“He said it would kill his mother if he took his own life …”

“She said suicide is against her religion …”

Simply writing “No evidence of suicidal/homicidal ideation” raises the question of whether you asked the patient if he or she has considered suicide or just looked for a sign indicating suicidality. Always ask and record the patient’s exact response.

4. Remember that other clinicians will view the chart to make decisions about your patient’s care. Consider this example:

“Patient just moved to this area and requests amitriptyline and chlorpromazine. The risks of combining these medications were explained to him, but he insisted, so will order.”

If another provider is to grant the patient’s request, more details are needed:

“Patient states that he has been on every antipsychotic and antidepressant on the market—including the newest drugs—over 20 years. He says nothing works for him except this combination. The potential anticholinergic and other severe adverse effects associated with this combination were explained to him, and his responses indicated that he clearly understands the risks. He states, ‘These are the only drugs that have kept me from hearing voices and being depressed and suicidal. I want to stay on this combination.’ ”

5. Write legibly. Many doctors are encouraged to write illegible notes as a defense against legal action. The reasoning: the defendant can testify to anything since no one can read the notes anyway.

Illegible notes annoy and frustrate the people who cannot read them and inspire a lack of trust and confidence in the doctor who wrote them. And they are not likely to fool a jury.

6. Respect patient privacy. Do not name or quote anyone who is not essential to the record. Identifying another patient by name or Social Security number—even the last 4 digits—is a breach of privacy. For example:

“Charlene claimed R2803 followed her into the rest room and raped her…”

Did patient R2803 actually do this? What if Charlene’s psychosis prompted her to make delusional claims about other patients and staff? If her case ends up in court, patient R2803 is named in connection with an unproven allegation. Naming R2803 in Charlene’s chart identifies him as a psychiatric patient at that facility, thus violating his privacy.

If your patient makes accusations toward another patient, describe the alleged encounter this way:

“Charlene was upset over an interaction she described with another patient. Staff allowed her time to ventilate, and (name/dose of sedative) was given. The incident was addressed with the other patient’s treatment team and staff … ”

7. Do not include complaints about other staff members, whether from the patient, staff, or a doctor.

Let’s say a resident pages his backup attending but receives no answer. Entering in the patient’s chart that “Dr. Smith was paged but did not answer” gives the impression that Dr. Smith is ignoring calls, when in fact any of the following may be true:

• the resident does not realize Dr. Smith traded on-call duty with another doctor
• the batteries in Dr. Smith’s pager died
• or Dr. Smith was home, available by telephone, with his pager tucked away in his briefcase.

If the doctor on call cannot be reached, call another doctor—a supervisor or department head—and document your conversation with him or her. Do not identify the doctor who was not available.

Supervisors should address doctor availability issues the following day. Such issues do not belong in a patient’s chart.

8. Document responses to and from other providers. When consulting another doctor for advice, describe the encounter and identify the doctor by name. For example:

“Dr. Mark Jones advised me to accommodate the patient’s request for discharge, because he has known the patient for many years and feels it is safe for the patient to come to see him at the clinic in the morning.”

9. When disregarding a consultant’s advice, clearly explain why. For example:

“Neurology consultant recommended stopping patient’s antipsychotic due to risk of tardive dyskinesia. This patient, however, has been on numerous antipsychotics over the years, and this is the only one that controls his schizophrenia. Patient is aware of the risk of tardive dyskinesia and does not find it problematic. Patient is competent and understands the need to weigh potential side effects against the medication’s benefits, and he prefers to continue the medication.”

10. Never enter derogatory or pejorative statements about a patient. As psychiatrists, we must convey a sense of concern and respect for the patient, regardless of diagnosis and presentation.

Rather than entering, “This patient is obviously lying about his history,” instead write, “This patient’s version of his history is at odds with that in previous hospital records.”

Related resources

• Selden BS, Schnitzer PG, Nolan FX. Medicolegal documentation of prehospital triage. Ann Emerg Med 1990;19:547-51.
• Bjorck JP, Brown J, Goodman M. Casebook for managing managed care: a self-study guide for treatment planning, documentation, and communication (1st ed). Washington, DC: American Psychiatric Association, 2000.
• Wiger DE. The clinical documentation sourcebook: a comprehensive collection of mental health practice forms, handouts, and records (2nd ed). New York: John Wiley &Sons, 1999.

Drug brand names

• Amitriptyline • Elavil
• Chlorpromazine • Thorazine
• Lithium • Eskalith, others

Progress notes must convey that the psychiatrist provided quality care and respected the patient’s condition and wishes. Knowing what information to include—and what to leave out—can help you and your colleagues avoid a malpractice judgment.

Follow these 10 dos and don’ts of writing progress notes:

1. Be concise. Document all necessary information but avoid extraneous details, such as in this example:

“Patient moved to Kansas at age 4. Her parents separated when she was 6 and they moved back to Chicago, then reunited and moved to Indiana, where father took a job as a shoe salesman. When he lost that job, they moved back to Chicago and divorced for good. Mother remarried a fireman, who was an alcoholic; they stayed together for 2 years until …”

Instead, simply write:

“Patient’s childhood was chaotic with many moves; her mother remarried x 3. No physical or sexual abuse …”

2. Include adequate details. Do not exclude information critical to explaining treatment decisions. Describe the symptoms the patient is reporting and the signs you see—or do not see.

This example offers insufficient detail:

“Patient’s parents told her that they just bought a new car. She recalled the first car they had gotten when she was little, and how that made her happy. She talked about the first car she owned. Plan: Add lithium …”

By contrast, the following example explicitly describes signs and symptoms. Also be sure to include a short explanation when changing, discontinuing, or adding a medication:

“Patient reports her mood is much improved. She cannot recall what made her feel so depressed last week. She is hyperverbal, talking rapidly, gesticulating as she talks—much more animated, as compared to psychomotor-retarded presentation of last week, when SSRI was started. Assess: Bipolar switch. Plan: Add lithium, 300 mg bid, and titrate.”

3. Be careful when describing treatment of a patient who is suicidal at presentation. Your notes must contain clear, well-reasoned explanations for:

• discontinuing suicide precautions
• not hospitalizing outpatients who express suicidal ideation.

If the patient attempts or commits suicide shortly after the visit, your progress note may be your best—and only—defense against a malpractice claim. This example offers no convincing argument that the patient will not attempt suicide:

“Patient reports that he feels better. He denies suicidal ideation. He thinks the antidepressant is working. Nursing notes indicate no problems. He would like to get dressed and take a walk outside …”

Instead, verbatim patient statements offer more-concrete proof that the patient wants to live:

“He said he is his family’s sole support and could never abandon them …”

“He said it would kill his mother if he took his own life …”

“She said suicide is against her religion …”

Simply writing “No evidence of suicidal/homicidal ideation” raises the question of whether you asked the patient if he or she has considered suicide or just looked for a sign indicating suicidality. Always ask and record the patient’s exact response.

4. Remember that other clinicians will view the chart to make decisions about your patient’s care. Consider this example:

“Patient just moved to this area and requests amitriptyline and chlorpromazine. The risks of combining these medications were explained to him, but he insisted, so will order.”

If another provider is to grant the patient’s request, more details are needed:

“Patient states that he has been on every antipsychotic and antidepressant on the market—including the newest drugs—over 20 years. He says nothing works for him except this combination. The potential anticholinergic and other severe adverse effects associated with this combination were explained to him, and his responses indicated that he clearly understands the risks. He states, ‘These are the only drugs that have kept me from hearing voices and being depressed and suicidal. I want to stay on this combination.’ ”

5. Write legibly. Many doctors are encouraged to write illegible notes as a defense against legal action. The reasoning: the defendant can testify to anything since no one can read the notes anyway.

Illegible notes annoy and frustrate the people who cannot read them and inspire a lack of trust and confidence in the doctor who wrote them. And they are not likely to fool a jury.

6. Respect patient privacy. Do not name or quote anyone who is not essential to the record. Identifying another patient by name or Social Security number—even the last 4 digits—is a breach of privacy. For example:

“Charlene claimed R2803 followed her into the rest room and raped her…”

Did patient R2803 actually do this? What if Charlene’s psychosis prompted her to make delusional claims about other patients and staff? If her case ends up in court, patient R2803 is named in connection with an unproven allegation. Naming R2803 in Charlene’s chart identifies him as a psychiatric patient at that facility, thus violating his privacy.

If your patient makes accusations toward another patient, describe the alleged encounter this way:

“Charlene was upset over an interaction she described with another patient. Staff allowed her time to ventilate, and (name/dose of sedative) was given. The incident was addressed with the other patient’s treatment team and staff … ”

7. Do not include complaints about other staff members, whether from the patient, staff, or a doctor.

Let’s say a resident pages his backup attending but receives no answer. Entering in the patient’s chart that “Dr. Smith was paged but did not answer” gives the impression that Dr. Smith is ignoring calls, when in fact any of the following may be true:

• the resident does not realize Dr. Smith traded on-call duty with another doctor
• the batteries in Dr. Smith’s pager died
• or Dr. Smith was home, available by telephone, with his pager tucked away in his briefcase.

If the doctor on call cannot be reached, call another doctor—a supervisor or department head—and document your conversation with him or her. Do not identify the doctor who was not available.

Supervisors should address doctor availability issues the following day. Such issues do not belong in a patient’s chart.

8. Document responses to and from other providers. When consulting another doctor for advice, describe the encounter and identify the doctor by name. For example:

“Dr. Mark Jones advised me to accommodate the patient’s request for discharge, because he has known the patient for many years and feels it is safe for the patient to come to see him at the clinic in the morning.”

9. When disregarding a consultant’s advice, clearly explain why. For example:

“Neurology consultant recommended stopping patient’s antipsychotic due to risk of tardive dyskinesia. This patient, however, has been on numerous antipsychotics over the years, and this is the only one that controls his schizophrenia. Patient is aware of the risk of tardive dyskinesia and does not find it problematic. Patient is competent and understands the need to weigh potential side effects against the medication’s benefits, and he prefers to continue the medication.”

10. Never enter derogatory or pejorative statements about a patient. As psychiatrists, we must convey a sense of concern and respect for the patient, regardless of diagnosis and presentation.

Rather than entering, “This patient is obviously lying about his history,” instead write, “This patient’s version of his history is at odds with that in previous hospital records.”

Related resources

• Selden BS, Schnitzer PG, Nolan FX. Medicolegal documentation of prehospital triage. Ann Emerg Med 1990;19:547-51.
• Bjorck JP, Brown J, Goodman M. Casebook for managing managed care: a self-study guide for treatment planning, documentation, and communication (1st ed). Washington, DC: American Psychiatric Association, 2000.
• Wiger DE. The clinical documentation sourcebook: a comprehensive collection of mental health practice forms, handouts, and records (2nd ed). New York: John Wiley &Sons, 1999.

Drug brand names

• Amitriptyline • Elavil
• Chlorpromazine • Thorazine
• Lithium • Eskalith, others

Progress notes must convey that the psychiatrist provided quality care and respected the patient’s condition and wishes. Knowing what information to include—and what to leave out—can help you and your colleagues avoid a malpractice judgment.

Follow these 10 dos and don’ts of writing progress notes:

1. Be concise. Document all necessary information but avoid extraneous details, such as in this example:

“Patient moved to Kansas at age 4. Her parents separated when she was 6 and they moved back to Chicago, then reunited and moved to Indiana, where father took a job as a shoe salesman. When he lost that job, they moved back to Chicago and divorced for good. Mother remarried a fireman, who was an alcoholic; they stayed together for 2 years until …”

Instead, simply write:

“Patient’s childhood was chaotic with many moves; her mother remarried x 3. No physical or sexual abuse …”

2. Include adequate details. Do not exclude information critical to explaining treatment decisions. Describe the symptoms the patient is reporting and the signs you see—or do not see.

This example offers insufficient detail:

“Patient’s parents told her that they just bought a new car. She recalled the first car they had gotten when she was little, and how that made her happy. She talked about the first car she owned. Plan: Add lithium …”

By contrast, the following example explicitly describes signs and symptoms. Also be sure to include a short explanation when changing, discontinuing, or adding a medication:

“Patient reports her mood is much improved. She cannot recall what made her feel so depressed last week. She is hyperverbal, talking rapidly, gesticulating as she talks—much more animated, as compared to psychomotor-retarded presentation of last week, when SSRI was started. Assess: Bipolar switch. Plan: Add lithium, 300 mg bid, and titrate.”

3. Be careful when describing treatment of a patient who is suicidal at presentation. Your notes must contain clear, well-reasoned explanations for:

• discontinuing suicide precautions
• not hospitalizing outpatients who express suicidal ideation.

If the patient attempts or commits suicide shortly after the visit, your progress note may be your best—and only—defense against a malpractice claim. This example offers no convincing argument that the patient will not attempt suicide:

“Patient reports that he feels better. He denies suicidal ideation. He thinks the antidepressant is working. Nursing notes indicate no problems. He would like to get dressed and take a walk outside …”

Instead, verbatim patient statements offer more-concrete proof that the patient wants to live:

“He said he is his family’s sole support and could never abandon them …”

“He said it would kill his mother if he took his own life …”

“She said suicide is against her religion …”

Simply writing “No evidence of suicidal/homicidal ideation” raises the question of whether you asked the patient if he or she has considered suicide or just looked for a sign indicating suicidality. Always ask and record the patient’s exact response.

4. Remember that other clinicians will view the chart to make decisions about your patient’s care. Consider this example:

“Patient just moved to this area and requests amitriptyline and chlorpromazine. The risks of combining these medications were explained to him, but he insisted, so will order.”

If another provider is to grant the patient’s request, more details are needed:

“Patient states that he has been on every antipsychotic and antidepressant on the market—including the newest drugs—over 20 years. He says nothing works for him except this combination. The potential anticholinergic and other severe adverse effects associated with this combination were explained to him, and his responses indicated that he clearly understands the risks. He states, ‘These are the only drugs that have kept me from hearing voices and being depressed and suicidal. I want to stay on this combination.’ ”

5. Write legibly. Many doctors are encouraged to write illegible notes as a defense against legal action. The reasoning: the defendant can testify to anything since no one can read the notes anyway.

Illegible notes annoy and frustrate the people who cannot read them and inspire a lack of trust and confidence in the doctor who wrote them. And they are not likely to fool a jury.

6. Respect patient privacy. Do not name or quote anyone who is not essential to the record. Identifying another patient by name or Social Security number—even the last 4 digits—is a breach of privacy. For example:

“Charlene claimed R2803 followed her into the rest room and raped her…”

Did patient R2803 actually do this? What if Charlene’s psychosis prompted her to make delusional claims about other patients and staff? If her case ends up in court, patient R2803 is named in connection with an unproven allegation. Naming R2803 in Charlene’s chart identifies him as a psychiatric patient at that facility, thus violating his privacy.

If your patient makes accusations toward another patient, describe the alleged encounter this way:

“Charlene was upset over an interaction she described with another patient. Staff allowed her time to ventilate, and (name/dose of sedative) was given. The incident was addressed with the other patient’s treatment team and staff … ”

7. Do not include complaints about other staff members, whether from the patient, staff, or a doctor.

Let’s say a resident pages his backup attending but receives no answer. Entering in the patient’s chart that “Dr. Smith was paged but did not answer” gives the impression that Dr. Smith is ignoring calls, when in fact any of the following may be true:

• the resident does not realize Dr. Smith traded on-call duty with another doctor
• the batteries in Dr. Smith’s pager died
• or Dr. Smith was home, available by telephone, with his pager tucked away in his briefcase.

If the doctor on call cannot be reached, call another doctor—a supervisor or department head—and document your conversation with him or her. Do not identify the doctor who was not available.

Supervisors should address doctor availability issues the following day. Such issues do not belong in a patient’s chart.

8. Document responses to and from other providers. When consulting another doctor for advice, describe the encounter and identify the doctor by name. For example:

“Dr. Mark Jones advised me to accommodate the patient’s request for discharge, because he has known the patient for many years and feels it is safe for the patient to come to see him at the clinic in the morning.”

9. When disregarding a consultant’s advice, clearly explain why. For example:

“Neurology consultant recommended stopping patient’s antipsychotic due to risk of tardive dyskinesia. This patient, however, has been on numerous antipsychotics over the years, and this is the only one that controls his schizophrenia. Patient is aware of the risk of tardive dyskinesia and does not find it problematic. Patient is competent and understands the need to weigh potential side effects against the medication’s benefits, and he prefers to continue the medication.”

10. Never enter derogatory or pejorative statements about a patient. As psychiatrists, we must convey a sense of concern and respect for the patient, regardless of diagnosis and presentation.

Rather than entering, “This patient is obviously lying about his history,” instead write, “This patient’s version of his history is at odds with that in previous hospital records.”

Related resources

• Selden BS, Schnitzer PG, Nolan FX. Medicolegal documentation of prehospital triage. Ann Emerg Med 1990;19:547-51.
• Bjorck JP, Brown J, Goodman M. Casebook for managing managed care: a self-study guide for treatment planning, documentation, and communication (1st ed). Washington, DC: American Psychiatric Association, 2000.
• Wiger DE. The clinical documentation sourcebook: a comprehensive collection of mental health practice forms, handouts, and records (2nd ed). New York: John Wiley &Sons, 1999.

Drug brand names

• Amitriptyline • Elavil
• Chlorpromazine • Thorazine
• Lithium • Eskalith, others

History: A mite disturbing

Mrs. K, age 60, a social worker, saw mites on her arm 3 months ago while going through a client’s old belongings. Since then, she reports, she and her house have become infested with mites.

Despite using copious amounts of lotions, baths, sprays, and prescription creams, she sees increasingly visible “creatures” all over her body and in her stool. Three doctors found no physical evidence of infestation, however, and she became indignant after one told her the problem is “in her head.”

A veterinarian treated Mrs. K’s cat for mites. Days later, Mrs. K suspected that the cat had become reinfested at home and returned it to the veterinarian. He assured her the cat was fine, but she was afraid to bring it home. The cat has remained at the veterinarian’s office—to the doctor’s displeasure—for weeks.

Two weeks after Mrs. K first spotted the mites, her husband, age 82, started believing he is infested. Mr. K, who is retired, has battled depression and drinks about a half-gallon of liquor daily.

After 2 months, Mrs. K quit her job for fear she would infest her co-workers, then locked herself and her husband in their house and allowed no visitors. Day and night for nearly 3 weeks, Mrs. K repeatedly vacuumed the house, shampooed the carpets, and sprayed the walls and furniture with a homemade insecticide. She taped the windows closed to keep bugs out and covered all furniture and surface areas with plastic. A toxic stench of insecticide and shampoo permeated every room.

A neighbor told Mrs. K’s son that his parents were locked inside their house. He came over and knocked on their door, but was refused entry. He eventually got Mrs. K out by threatening to call the police, then brought her to the emergency room.

At presentation, Mrs. K’s right leg has scratches and scabs caused by frequent scratching at mites she saw there. Her hands are reddened and dry, suggesting chemical dermatitis caused by cleaning and repeated insecticide use. Ritual cleaning and spraying has kept her from eating or sleeping; she has lost 12 lbs over 3 weeks and looks pale and tired.

A recovered alcoholic, Mrs. K has been sober for 12 years. She has no other psychiatric, medical, or dermatologic history, and has few social contacts beyond her family and workplace acquaintances.

Blood chemistry, CBC, and urine drug test results are normal. Head MRI reveal no neurologic abnormalities. Her Mini-Mental State Examination (MMSE) score (29/30) indicates no cognitive impairment.

Mrs. K is hospitalized to separate her from her allegedly bug-infested household and husband. At intake, she is panicked over leaving her husband alone and distressed that no one except she and her husband can see the bugs infesting their house and covering her skin. She asks doctors to test a small piece of toilet paper, which she says contains a sample of the bugs. She also fears that she infested her son by letting him into her house.

poll here

The authors’ observations

Mrs. K’s presentation and clinical course suggest delusional parasitosis, a fixed false belief of a parasitic infestation that can cause significant social and occupational dysfunction and medical problems. One patient calls this disorder “bugaphobia.”

The disorder may start as a self-perceived invisible infestation and evolve into visual hallucinations of bugs. Patients usually believe their skin is infested; some believe their internal organs, gums, or skin and internal organs are infested.^1,2

Table 1

Medical conditions that may precede delusional parasitosis

Some patients misinterpret scabs, abrasions, or skin irritation secondary to pesticide use as signs of infestation. Delusional parasitosis can also develop after a real, one-time infestation, as may have happened with Mrs. K.

Convinced they are infested, patients consult multiple providers—including dermatologists, gastroenterologists, and ophthalmologists—in search of the “right” treatment. They undergo numerous tests or procedures and repeatedly apply prescription creams and lotions, leading to chemical dermatitis. Patients often try to prove they are infested by bringing skin, dirt, or toilet tissue samples to doctors—this is called the “matchbox sign” because patients generally bring these samples in small boxes.⁴ They also may repeatedly ask veterinarians to disinfest their pets.

Box

Delusional parasitosis is most often found in socially isolated women age >40 of average or higher intelligence. Persons in some cultures may be more susceptible than others to some types of parasitic delusions. For example, several persons in India who considered ear cleanliness crucial to attaining cultural and spiritual purity reported having ear infestation.⁷

Delusional parasitosis also is associated with:

• medical conditions (Table 1)⁶
  
• use of cocaine, amphetamines,⁸ corticosteroids,^3,9 or phenelzine¹⁰
  
• occipital-temporal cerebral infarction¹¹
  
• cognitive impairment related to dementia, depression, mental retardation, or schizophrenia/schizophreniform disorder.
  

Mrs. K’s delusional parasitosis may be a primary psychiatric disorder (Box). She is medically healthy and does not use drugs or alcohol. Her MMSE score is essentially normal, and she exhibited no psychotic symptoms or loss of function before her first mite sighting.

Diagnosis. Delusional parasitosis is diagnosed as delusional disorder, somatic type, if symptoms persist >1 month. Thorough laboratory and neurologic evaluation is recommended to rule out medical causes (Table 2). Eliminate schizophrenia and schizophreniform disorder with a detailed patient history and cognitive testing.

Also check for a comorbid psychiatric disorder that may be perpetuating the delusion. Delusional parasitosis often co-occurs with axis I disorders including major depressive disorder, substance abuse, dementia, and mental retardation.

poll here

The authors’ observations

Mr. K’s “bugaphobia” most likely was a form of shared secondary delusion called folie-a-deux. Between 11% and 25% of persons with primary delusional parasitosis induce secondary delusional parasitosis in another person, usually a spouse or longtime friend.² About 50% of folie-a-deux disorders involve a married couple. Often both partners are socially isolated.⁴

poll here

Treatment: Between two worlds

Mrs. K was given risperidone, 2 mg/d, for delusions and anxiety, and escitalopram, 10 mg/d, preventatively for a suspected underlying depression.

As her symptoms began to clear across 2 to 3 days, Mrs. K realized most times that she was not infested, but on occasion still feared that she was. She continued to worry about her husband being alone in a mite-infested house. We reassured her that her husband would be OK and told her to let us know if the mites resurfaced on her skin.

The authors’ observations

Building rapport. When treating delusional parasitosis, be accepting and non-confrontational. These patients tend to switch doctors until they find someone who understands their problem. Developing rapport can promote treatment adherence and prevent or minimize relapse.

Table 2

5 steps to confirm ‘bugaphobia’

Also communicate with other specialists to gauge medication history, confirm test findings, and rule out medical causes.

Pharmacotherapy. If symptoms do not resolve after 1 or 2 days of observation, look for a comorbid medical or mental disorder. Prescribe an atypical antipsychotic such as risperidone, 2 to 4 mg/d, or olanzapine, 2.5 mg/d, both of which have been effective against delusional parasitosis.^14,16 Keep dosages low to reduce risk of sedation, extrapyramidal symptoms (EPS), and tardive dyskinesia.

Suggesting a psychotropic to patients who are convinced their problem is not psychiatric can be difficult. Try saying:

• Some people are more sensitive than others to sensations on their skin or in their body. This medication will help you tolerate the sensations.”
  
• or, “This drug will help reduce the anxiety your problem is causing.”
  

Pimozide has shown efficacy against delusional parasitosis in placebo-controlled trials,^17,18 but it can alter cardiac conduction, especially at higherthan-recommended dosages. Start pimozide at 1 mg/d and increase by 1 mg/week until clinical response is achieved. Most patients respond to dosages used to treat psychotic disorders (4 to 10 mg/d).¹⁹ Order a baseline and periodic ECG to monitor for QTc prolongation, and do an abnormal involuntary movement scale examination every 3 to 6 months to test for EPS.

Other treatments that have shown benefit in case reports include naloxone, 10 mg/d;²⁰ haloperidol, 10 mg/d; trifluoperazine, 15 mg/d; chlorpromazine, 150 to 300 mg/d; and electroconvulsive therapy.⁷

We have found that prognosis usually is poor after first- and second-line treatments have failed. Continue to search for a missed disorder, and add an antidepressant if an underlying depression is found or suspected.

Psychotherapy. Perform supportive and harm reduction psychotherapy immediately after diagnosis. Supportive, rapport-building approaches can get the patient to comfortably discuss the issues that led to the delusion and help him/her confront a relapse. Harm reduction can discourage patients from requesting unnecessary invasive tests, using medications and toxic insecticides, or other potentially harmful behaviors.

Cognitive-behavioral therapy may help some patients with refractory delusional parasitosis, if they have enough insight to continue treatment.

Follow-up: A bug-free future

Mrs. K was released from the hospital after 4 days, and her delusional symptoms were gone after another 3 days. We followed her for 6 months.

Upon discharge, Mrs. K and her cat moved in with her daughter’s family. Within a few weeks she was able to visit her workplace and explain what had happened. She stopped taking risperidone after 2 weeks because of excessive sedation. No depressive symptoms were present after 3 months; escitalopram was stopped.

Mrs. K’s husband continued to drink and confine himself to the house. Upon visiting him, she was horrified to find the furniture still covered with plastic and the windows taped shut. Mrs. K threatened to divorce him if he did not seek help. He eventually was treated and has been sober—and bug-free—for 15 months.

Related resources

• Bohart Museum of Entomology, University of California, Davis: Delusional parasitosis. http://delusion.ucdavis.edu.
  

• Chlorpromazine • Thorazine
  
• Escitalopram • Lexapro
  
• Haloperidol • Haldol
  
• naloxone • Narcan
  
• Olanzapine • Zyprexa
  
• Pimozide • Orap
  
• Phenelzine • Nardil
  
• Risperidone • Risperdal
  
• Trifluoperazine • Stelazine
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Hauser receives research/grant support from and is a speaker for AstraZeneca Pharmaceuticals, Eli Lilly and Co., GlaxoSmithKline, and Hoffman LaRoche. He is also receives research/grant support from Schering-Plough Corp. and is a speaker for Abbott Laboratories and Janssen Pharmaceutica.

History: A mite disturbing

Mrs. K, age 60, a social worker, saw mites on her arm 3 months ago while going through a client’s old belongings. Since then, she reports, she and her house have become infested with mites.

Despite using copious amounts of lotions, baths, sprays, and prescription creams, she sees increasingly visible “creatures” all over her body and in her stool. Three doctors found no physical evidence of infestation, however, and she became indignant after one told her the problem is “in her head.”

A veterinarian treated Mrs. K’s cat for mites. Days later, Mrs. K suspected that the cat had become reinfested at home and returned it to the veterinarian. He assured her the cat was fine, but she was afraid to bring it home. The cat has remained at the veterinarian’s office—to the doctor’s displeasure—for weeks.

Two weeks after Mrs. K first spotted the mites, her husband, age 82, started believing he is infested. Mr. K, who is retired, has battled depression and drinks about a half-gallon of liquor daily.

After 2 months, Mrs. K quit her job for fear she would infest her co-workers, then locked herself and her husband in their house and allowed no visitors. Day and night for nearly 3 weeks, Mrs. K repeatedly vacuumed the house, shampooed the carpets, and sprayed the walls and furniture with a homemade insecticide. She taped the windows closed to keep bugs out and covered all furniture and surface areas with plastic. A toxic stench of insecticide and shampoo permeated every room.

A neighbor told Mrs. K’s son that his parents were locked inside their house. He came over and knocked on their door, but was refused entry. He eventually got Mrs. K out by threatening to call the police, then brought her to the emergency room.

At presentation, Mrs. K’s right leg has scratches and scabs caused by frequent scratching at mites she saw there. Her hands are reddened and dry, suggesting chemical dermatitis caused by cleaning and repeated insecticide use. Ritual cleaning and spraying has kept her from eating or sleeping; she has lost 12 lbs over 3 weeks and looks pale and tired.

A recovered alcoholic, Mrs. K has been sober for 12 years. She has no other psychiatric, medical, or dermatologic history, and has few social contacts beyond her family and workplace acquaintances.

Blood chemistry, CBC, and urine drug test results are normal. Head MRI reveal no neurologic abnormalities. Her Mini-Mental State Examination (MMSE) score (29/30) indicates no cognitive impairment.

Mrs. K is hospitalized to separate her from her allegedly bug-infested household and husband. At intake, she is panicked over leaving her husband alone and distressed that no one except she and her husband can see the bugs infesting their house and covering her skin. She asks doctors to test a small piece of toilet paper, which she says contains a sample of the bugs. She also fears that she infested her son by letting him into her house.

poll here

The authors’ observations

Mrs. K’s presentation and clinical course suggest delusional parasitosis, a fixed false belief of a parasitic infestation that can cause significant social and occupational dysfunction and medical problems. One patient calls this disorder “bugaphobia.”

The disorder may start as a self-perceived invisible infestation and evolve into visual hallucinations of bugs. Patients usually believe their skin is infested; some believe their internal organs, gums, or skin and internal organs are infested.^1,2

Table 1

Medical conditions that may precede delusional parasitosis

Some patients misinterpret scabs, abrasions, or skin irritation secondary to pesticide use as signs of infestation. Delusional parasitosis can also develop after a real, one-time infestation, as may have happened with Mrs. K.

Convinced they are infested, patients consult multiple providers—including dermatologists, gastroenterologists, and ophthalmologists—in search of the “right” treatment. They undergo numerous tests or procedures and repeatedly apply prescription creams and lotions, leading to chemical dermatitis. Patients often try to prove they are infested by bringing skin, dirt, or toilet tissue samples to doctors—this is called the “matchbox sign” because patients generally bring these samples in small boxes.⁴ They also may repeatedly ask veterinarians to disinfest their pets.

Box

Delusional parasitosis is most often found in socially isolated women age >40 of average or higher intelligence. Persons in some cultures may be more susceptible than others to some types of parasitic delusions. For example, several persons in India who considered ear cleanliness crucial to attaining cultural and spiritual purity reported having ear infestation.⁷

Delusional parasitosis also is associated with:

• medical conditions (Table 1)⁶
  
• use of cocaine, amphetamines,⁸ corticosteroids,^3,9 or phenelzine¹⁰
  
• occipital-temporal cerebral infarction¹¹
  
• cognitive impairment related to dementia, depression, mental retardation, or schizophrenia/schizophreniform disorder.
  

Mrs. K’s delusional parasitosis may be a primary psychiatric disorder (Box). She is medically healthy and does not use drugs or alcohol. Her MMSE score is essentially normal, and she exhibited no psychotic symptoms or loss of function before her first mite sighting.

Diagnosis. Delusional parasitosis is diagnosed as delusional disorder, somatic type, if symptoms persist >1 month. Thorough laboratory and neurologic evaluation is recommended to rule out medical causes (Table 2). Eliminate schizophrenia and schizophreniform disorder with a detailed patient history and cognitive testing.

Also check for a comorbid psychiatric disorder that may be perpetuating the delusion. Delusional parasitosis often co-occurs with axis I disorders including major depressive disorder, substance abuse, dementia, and mental retardation.

poll here

The authors’ observations

Mr. K’s “bugaphobia” most likely was a form of shared secondary delusion called folie-a-deux. Between 11% and 25% of persons with primary delusional parasitosis induce secondary delusional parasitosis in another person, usually a spouse or longtime friend.² About 50% of folie-a-deux disorders involve a married couple. Often both partners are socially isolated.⁴

poll here

Treatment: Between two worlds

Mrs. K was given risperidone, 2 mg/d, for delusions and anxiety, and escitalopram, 10 mg/d, preventatively for a suspected underlying depression.

As her symptoms began to clear across 2 to 3 days, Mrs. K realized most times that she was not infested, but on occasion still feared that she was. She continued to worry about her husband being alone in a mite-infested house. We reassured her that her husband would be OK and told her to let us know if the mites resurfaced on her skin.

The authors’ observations

Building rapport. When treating delusional parasitosis, be accepting and non-confrontational. These patients tend to switch doctors until they find someone who understands their problem. Developing rapport can promote treatment adherence and prevent or minimize relapse.

Table 2

5 steps to confirm ‘bugaphobia’

Also communicate with other specialists to gauge medication history, confirm test findings, and rule out medical causes.

Pharmacotherapy. If symptoms do not resolve after 1 or 2 days of observation, look for a comorbid medical or mental disorder. Prescribe an atypical antipsychotic such as risperidone, 2 to 4 mg/d, or olanzapine, 2.5 mg/d, both of which have been effective against delusional parasitosis.^14,16 Keep dosages low to reduce risk of sedation, extrapyramidal symptoms (EPS), and tardive dyskinesia.

Suggesting a psychotropic to patients who are convinced their problem is not psychiatric can be difficult. Try saying:

• Some people are more sensitive than others to sensations on their skin or in their body. This medication will help you tolerate the sensations.”
  
• or, “This drug will help reduce the anxiety your problem is causing.”
  

Pimozide has shown efficacy against delusional parasitosis in placebo-controlled trials,^17,18 but it can alter cardiac conduction, especially at higherthan-recommended dosages. Start pimozide at 1 mg/d and increase by 1 mg/week until clinical response is achieved. Most patients respond to dosages used to treat psychotic disorders (4 to 10 mg/d).¹⁹ Order a baseline and periodic ECG to monitor for QTc prolongation, and do an abnormal involuntary movement scale examination every 3 to 6 months to test for EPS.

Other treatments that have shown benefit in case reports include naloxone, 10 mg/d;²⁰ haloperidol, 10 mg/d; trifluoperazine, 15 mg/d; chlorpromazine, 150 to 300 mg/d; and electroconvulsive therapy.⁷

We have found that prognosis usually is poor after first- and second-line treatments have failed. Continue to search for a missed disorder, and add an antidepressant if an underlying depression is found or suspected.

Psychotherapy. Perform supportive and harm reduction psychotherapy immediately after diagnosis. Supportive, rapport-building approaches can get the patient to comfortably discuss the issues that led to the delusion and help him/her confront a relapse. Harm reduction can discourage patients from requesting unnecessary invasive tests, using medications and toxic insecticides, or other potentially harmful behaviors.

Cognitive-behavioral therapy may help some patients with refractory delusional parasitosis, if they have enough insight to continue treatment.

Follow-up: A bug-free future

Mrs. K was released from the hospital after 4 days, and her delusional symptoms were gone after another 3 days. We followed her for 6 months.

Upon discharge, Mrs. K and her cat moved in with her daughter’s family. Within a few weeks she was able to visit her workplace and explain what had happened. She stopped taking risperidone after 2 weeks because of excessive sedation. No depressive symptoms were present after 3 months; escitalopram was stopped.

Mrs. K’s husband continued to drink and confine himself to the house. Upon visiting him, she was horrified to find the furniture still covered with plastic and the windows taped shut. Mrs. K threatened to divorce him if he did not seek help. He eventually was treated and has been sober—and bug-free—for 15 months.

Related resources

• Bohart Museum of Entomology, University of California, Davis: Delusional parasitosis. http://delusion.ucdavis.edu.
  

• Chlorpromazine • Thorazine
  
• Escitalopram • Lexapro
  
• Haloperidol • Haldol
  
• naloxone • Narcan
  
• Olanzapine • Zyprexa
  
• Pimozide • Orap
  
• Phenelzine • Nardil
  
• Risperidone • Risperdal
  
• Trifluoperazine • Stelazine
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Hauser receives research/grant support from and is a speaker for AstraZeneca Pharmaceuticals, Eli Lilly and Co., GlaxoSmithKline, and Hoffman LaRoche. He is also receives research/grant support from Schering-Plough Corp. and is a speaker for Abbott Laboratories and Janssen Pharmaceutica.

History: A mite disturbing

Mrs. K, age 60, a social worker, saw mites on her arm 3 months ago while going through a client’s old belongings. Since then, she reports, she and her house have become infested with mites.

Despite using copious amounts of lotions, baths, sprays, and prescription creams, she sees increasingly visible “creatures” all over her body and in her stool. Three doctors found no physical evidence of infestation, however, and she became indignant after one told her the problem is “in her head.”

A veterinarian treated Mrs. K’s cat for mites. Days later, Mrs. K suspected that the cat had become reinfested at home and returned it to the veterinarian. He assured her the cat was fine, but she was afraid to bring it home. The cat has remained at the veterinarian’s office—to the doctor’s displeasure—for weeks.

Two weeks after Mrs. K first spotted the mites, her husband, age 82, started believing he is infested. Mr. K, who is retired, has battled depression and drinks about a half-gallon of liquor daily.

After 2 months, Mrs. K quit her job for fear she would infest her co-workers, then locked herself and her husband in their house and allowed no visitors. Day and night for nearly 3 weeks, Mrs. K repeatedly vacuumed the house, shampooed the carpets, and sprayed the walls and furniture with a homemade insecticide. She taped the windows closed to keep bugs out and covered all furniture and surface areas with plastic. A toxic stench of insecticide and shampoo permeated every room.

A neighbor told Mrs. K’s son that his parents were locked inside their house. He came over and knocked on their door, but was refused entry. He eventually got Mrs. K out by threatening to call the police, then brought her to the emergency room.

At presentation, Mrs. K’s right leg has scratches and scabs caused by frequent scratching at mites she saw there. Her hands are reddened and dry, suggesting chemical dermatitis caused by cleaning and repeated insecticide use. Ritual cleaning and spraying has kept her from eating or sleeping; she has lost 12 lbs over 3 weeks and looks pale and tired.

A recovered alcoholic, Mrs. K has been sober for 12 years. She has no other psychiatric, medical, or dermatologic history, and has few social contacts beyond her family and workplace acquaintances.

Blood chemistry, CBC, and urine drug test results are normal. Head MRI reveal no neurologic abnormalities. Her Mini-Mental State Examination (MMSE) score (29/30) indicates no cognitive impairment.

Mrs. K is hospitalized to separate her from her allegedly bug-infested household and husband. At intake, she is panicked over leaving her husband alone and distressed that no one except she and her husband can see the bugs infesting their house and covering her skin. She asks doctors to test a small piece of toilet paper, which she says contains a sample of the bugs. She also fears that she infested her son by letting him into her house.

poll here

The authors’ observations

Mrs. K’s presentation and clinical course suggest delusional parasitosis, a fixed false belief of a parasitic infestation that can cause significant social and occupational dysfunction and medical problems. One patient calls this disorder “bugaphobia.”

The disorder may start as a self-perceived invisible infestation and evolve into visual hallucinations of bugs. Patients usually believe their skin is infested; some believe their internal organs, gums, or skin and internal organs are infested.^1,2

Table 1

Medical conditions that may precede delusional parasitosis

Some patients misinterpret scabs, abrasions, or skin irritation secondary to pesticide use as signs of infestation. Delusional parasitosis can also develop after a real, one-time infestation, as may have happened with Mrs. K.

Convinced they are infested, patients consult multiple providers—including dermatologists, gastroenterologists, and ophthalmologists—in search of the “right” treatment. They undergo numerous tests or procedures and repeatedly apply prescription creams and lotions, leading to chemical dermatitis. Patients often try to prove they are infested by bringing skin, dirt, or toilet tissue samples to doctors—this is called the “matchbox sign” because patients generally bring these samples in small boxes.⁴ They also may repeatedly ask veterinarians to disinfest their pets.

Box

Delusional parasitosis is most often found in socially isolated women age >40 of average or higher intelligence. Persons in some cultures may be more susceptible than others to some types of parasitic delusions. For example, several persons in India who considered ear cleanliness crucial to attaining cultural and spiritual purity reported having ear infestation.⁷

Delusional parasitosis also is associated with:

• medical conditions (Table 1)⁶
  
• use of cocaine, amphetamines,⁸ corticosteroids,^3,9 or phenelzine¹⁰
  
• occipital-temporal cerebral infarction¹¹
  
• cognitive impairment related to dementia, depression, mental retardation, or schizophrenia/schizophreniform disorder.
  

Mrs. K’s delusional parasitosis may be a primary psychiatric disorder (Box). She is medically healthy and does not use drugs or alcohol. Her MMSE score is essentially normal, and she exhibited no psychotic symptoms or loss of function before her first mite sighting.

Diagnosis. Delusional parasitosis is diagnosed as delusional disorder, somatic type, if symptoms persist >1 month. Thorough laboratory and neurologic evaluation is recommended to rule out medical causes (Table 2). Eliminate schizophrenia and schizophreniform disorder with a detailed patient history and cognitive testing.

Also check for a comorbid psychiatric disorder that may be perpetuating the delusion. Delusional parasitosis often co-occurs with axis I disorders including major depressive disorder, substance abuse, dementia, and mental retardation.

poll here

The authors’ observations

Mr. K’s “bugaphobia” most likely was a form of shared secondary delusion called folie-a-deux. Between 11% and 25% of persons with primary delusional parasitosis induce secondary delusional parasitosis in another person, usually a spouse or longtime friend.² About 50% of folie-a-deux disorders involve a married couple. Often both partners are socially isolated.⁴

poll here

Treatment: Between two worlds

Mrs. K was given risperidone, 2 mg/d, for delusions and anxiety, and escitalopram, 10 mg/d, preventatively for a suspected underlying depression.

As her symptoms began to clear across 2 to 3 days, Mrs. K realized most times that she was not infested, but on occasion still feared that she was. She continued to worry about her husband being alone in a mite-infested house. We reassured her that her husband would be OK and told her to let us know if the mites resurfaced on her skin.

The authors’ observations

Building rapport. When treating delusional parasitosis, be accepting and non-confrontational. These patients tend to switch doctors until they find someone who understands their problem. Developing rapport can promote treatment adherence and prevent or minimize relapse.

Table 2

5 steps to confirm ‘bugaphobia’

Also communicate with other specialists to gauge medication history, confirm test findings, and rule out medical causes.

Pharmacotherapy. If symptoms do not resolve after 1 or 2 days of observation, look for a comorbid medical or mental disorder. Prescribe an atypical antipsychotic such as risperidone, 2 to 4 mg/d, or olanzapine, 2.5 mg/d, both of which have been effective against delusional parasitosis.^14,16 Keep dosages low to reduce risk of sedation, extrapyramidal symptoms (EPS), and tardive dyskinesia.

Suggesting a psychotropic to patients who are convinced their problem is not psychiatric can be difficult. Try saying:

• Some people are more sensitive than others to sensations on their skin or in their body. This medication will help you tolerate the sensations.”
  
• or, “This drug will help reduce the anxiety your problem is causing.”
  

Pimozide has shown efficacy against delusional parasitosis in placebo-controlled trials,^17,18 but it can alter cardiac conduction, especially at higherthan-recommended dosages. Start pimozide at 1 mg/d and increase by 1 mg/week until clinical response is achieved. Most patients respond to dosages used to treat psychotic disorders (4 to 10 mg/d).¹⁹ Order a baseline and periodic ECG to monitor for QTc prolongation, and do an abnormal involuntary movement scale examination every 3 to 6 months to test for EPS.

Other treatments that have shown benefit in case reports include naloxone, 10 mg/d;²⁰ haloperidol, 10 mg/d; trifluoperazine, 15 mg/d; chlorpromazine, 150 to 300 mg/d; and electroconvulsive therapy.⁷

We have found that prognosis usually is poor after first- and second-line treatments have failed. Continue to search for a missed disorder, and add an antidepressant if an underlying depression is found or suspected.

Psychotherapy. Perform supportive and harm reduction psychotherapy immediately after diagnosis. Supportive, rapport-building approaches can get the patient to comfortably discuss the issues that led to the delusion and help him/her confront a relapse. Harm reduction can discourage patients from requesting unnecessary invasive tests, using medications and toxic insecticides, or other potentially harmful behaviors.

Cognitive-behavioral therapy may help some patients with refractory delusional parasitosis, if they have enough insight to continue treatment.

Follow-up: A bug-free future

Mrs. K was released from the hospital after 4 days, and her delusional symptoms were gone after another 3 days. We followed her for 6 months.

Upon discharge, Mrs. K and her cat moved in with her daughter’s family. Within a few weeks she was able to visit her workplace and explain what had happened. She stopped taking risperidone after 2 weeks because of excessive sedation. No depressive symptoms were present after 3 months; escitalopram was stopped.

Mrs. K’s husband continued to drink and confine himself to the house. Upon visiting him, she was horrified to find the furniture still covered with plastic and the windows taped shut. Mrs. K threatened to divorce him if he did not seek help. He eventually was treated and has been sober—and bug-free—for 15 months.

Related resources

• Bohart Museum of Entomology, University of California, Davis: Delusional parasitosis. http://delusion.ucdavis.edu.
  

• Chlorpromazine • Thorazine
  
• Escitalopram • Lexapro
  
• Haloperidol • Haldol
  
• naloxone • Narcan
  
• Olanzapine • Zyprexa
  
• Pimozide • Orap
  
• Phenelzine • Nardil
  
• Risperidone • Risperdal
  
• Trifluoperazine • Stelazine
  

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Hauser receives research/grant support from and is a speaker for AstraZeneca Pharmaceuticals, Eli Lilly and Co., GlaxoSmithKline, and Hoffman LaRoche. He is also receives research/grant support from Schering-Plough Corp. and is a speaker for Abbott Laboratories and Janssen Pharmaceutica.

Three myths about cigarette smoking may explain why psychiatrists rarely intervene in their patients’ tobacco dependence:

• Cigarette smoking is an incurable habit in psychiatric patients and thus not worth the effort of intervening.
  
• Cigarette smoking is an acceptable form of self-medication in persons with psychiatric illness.
  
• Quitting smoking will worsen psychiatric symptoms.
  

Smoking by psychiatric patients is treatable, however, and evidence proves that many can quit.¹ This article rebuts the “why-bother?” myths and provides practical tips on how to more effectively help psychiatric patients stop smoking.

DEBUNKING THREE MYTHS

Mentally ill women and men consume nearly one-half (44%) of the cigarettes smoked in the United States (Table 1)^1-3 and thus are at high risk for tobacco-related premature death, cancer, cardiovascular disease, and respiratory disorders. Although recognized as a leading cause of death, cigarette smoking by psychiatric patients frequently goes unaddressed, contributing to excess mortality in this population.⁴

Table 1

Cigarette smoking: An epidemic among psychiatric patients

• psychiatrists seldom (6,7
  
• when counseling did occur, nicotine replacement therapy was not prescribed.⁶
  

Tobacco dependence is a syndrome with strong genetic and biologic roots. Family, twin, and adoption studies show consistently that tobacco dependence is genetically mediated.⁸ Genetic polymorphisms are being identified that may modify an individual’s risk for developing nicotine dependence—such as the gene encoding the cytochrome P-450 2A6 isoenzyme (CYP 2A6) that metabolizes nicotine to cotinine.⁹ Disturbed nicotinic receptor functioning has been shown in persons with schizophrenia, mood disorders, anxiety disorders, and attention-deficit/hyperactivity disorders.^3,10,11

Tobacco dependence is a chronic, relapsing condition that usually requires repeated intervention to motivate patients to try to quit and to help those who are willing to quit to succeed. Effective smoking cessation aids include:

• behavioral therapy (brief physician advice, problem-solving skills/skills training)
  
• pharmacologic therapy (nicotine replacement, sustained-release bupropion).¹²
  

Is smoking ‘self-medication’? Compelling evidence indicates that cholinergic mechanisms and nicotinic receptors (nAChRs) are involved in the pathophysiology of schizophrenia and other neuropsychiatric disorders.^3,10 Nicotine administration appears to improve sensory-processing and cognitive deficits observed in schizophrenia.^2,3 Moreover, the association between depression and smoking¹³ —and tobacco smoke’s monoamine oxidase-inhibiting and other psychoactive properties¹⁴ —have led some to posit that cigarette smoking may have antidepressant actions.¹⁰

For all these reasons, some authors have speculated that tobacco use may be a form of self-medication among the psychiatrically ill.³ The problem with this hypothesis, however, is that tobacco smoke is—at best—an untested and potentially lethal cognitive enhancer, antidepressant, or anxiolytic. Animal and human studies may find therapeutic effects of acute nicotine administration, but the cognitive effects of chronic tobacco smoking are not known.

Table 2

5 ‘A’s of brief clinical intervention for tobacco dependence

Adverse effects from quitting? Smokers with a history of major depressive disorder have been shown to be at risk to:

• develop another depressive episode after they quit smoking¹⁵
  
• experience more severe withdrawal symptoms during abstinence, compared with smokers with no history of depression.^13,16
  

Concerns that substance-abusing patients should not attempt to quit smoking during alcohol and other drug dependence treatment are also unsubstantiated. Rather than exacerbating drug addiction, smoking cessation has been found to improve addicts’ abstinence rates.¹⁹

USING AVAILABLE THERAPIES

Evidence is insufficient so far to show whether psychiatrically ill smokers would benefit more from specially tailored cessation treatments than from standard treatments, according to the 2000 U.S. Public Health Service clinical practice guide.¹² Thus, while researchers try to resolve this issue, psychiatrists are left to use medications found to be effective in smokers overall.

Clinical vignette. Mr. J, age 45, has paranoid-type schizophrenia and has been smoking at least two packs of cigarettes daily for 25 years. He complains of a productive cough and expresses interest in quitting smoking when his psychiatrist raises this topic.

His persecutory delusions are well-controlled on olanzapine, 10 mg/d. He is adhering with his medications and participating in weekly group counseling that provides supportive therapy for patients with serious mental illness.

In this schizophrenic smoker who is willing to try to quit, the psychiatrist performed the first three of “5 ‘A’s” (Table 2) of brief clinical intervention for tobacco dependence.^5,12 The next steps are to assist the patient’s effort to quit and arrange follow-up.

When to quit. The best time for a smoker with psychiatric illness to try to quit is when he or she:

• is psychiatrically stable
  
• is not in crisis
  
• has no recent or planned psychiatric drug changes.
  

Smoking cessation may increase blood levels of these psychotropics

Olanzapine’s clearance is approximately 40% higher in smokers than in nonsmokers. The psychiatrist discussed this with Mr. J and:

• asked him to call if side effects develop during the quit attempt
  
• scheduled more-frequent appointments to monitor side effects.
  

Mr. J’s schizophrenia is stable on maintenance therapy with an atypical antipsychotic. Schizophrenic smokers taking atypicals may be more able to quit smoking with NRT or sustained-release bupropion, compared with those taking conventional antipsychotics.²

The psychiatrist also determined that Mr. J had tried to quit smoking three times. Two of these attempts were done “cold turkey,” without pharmacotherapy, and one involved using nicotine gum. Mr. J said that although the gum “worked well at first,” he stopped using it because it was expensive and made his mouth sore. This information helped the psychiatrist choose medication for this quit attempt.

Most smoking cessation guidelines rely on a stepped-care approach, progressing from minimal to more-intensive interventions as needed.⁵ Mr. J’s psychiatrist devised an intensive treatment plan because:

• Mr. J has tried to quit before
  
• schizophrenic patients generally have more difficulty quitting and are more nicotine-dependent than other smokers.
  

Table 4

Nicotine replacement and other options for smoking cessation

Follow-up. Recognizing that most relapses occur in the first few days of quitting, the psychiatrist sets Mr. J’s first follow-up appointment for the day after his TQD to assess:

• whether he has smoked and number of cigarettes smoked per day
  
• presence and severity of withdrawal symptoms
  
• onset of psychiatric symptoms
  
• treatment adherence
  
• how he is handling high-risk situations and urges to smoke
  
• medication side effects.⁶
  

Related resources

• American Psychiatric Association. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry 1996; 53(153[suppl]): 1-31.
  
• Fiore MC, Bailey WC, Cohen SJ, et.al. Treating tobacco use and dependence. Clinical practice guideline. Rockville, MD: U.S. Public Health Service, 2000. http://www.ahcpr.gov/path/tobacco.htm. Accessed Dec. 13, 2004.
  

• Amantadine • Symmetrel
  
• Bupropion • Wellbutrin SR, Zyban
  
• Clonidine • Catapres
  
• Nicotine nasal spray • Nicotrol NS
  
• Nicotine polacrilex • Nicorette
  
• Nicotine replacement patch • Nicoderm CQ, Nicotrol, others
  
• Nicotine vapor inhaler • Nicotrol Inhaler
  
• Nortriptyline •Aventyl, Pamelor
  

Dr. Anthenelli receives grant/research support from Sanofi-Aventis and Ortho-McNeil Pharmaceuticals and is a consultant and speaker for Sanofi-Aventis.

Acknowledgments

The author would like to thank Reene Cantwell for technical assistance in preparing this manuscript. This work was supported by grants R01 AA13307 and R01 AA13957 from the National Institute on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs.

Three myths about cigarette smoking may explain why psychiatrists rarely intervene in their patients’ tobacco dependence:

• Cigarette smoking is an incurable habit in psychiatric patients and thus not worth the effort of intervening.
  
• Cigarette smoking is an acceptable form of self-medication in persons with psychiatric illness.
  
• Quitting smoking will worsen psychiatric symptoms.
  

Smoking by psychiatric patients is treatable, however, and evidence proves that many can quit.¹ This article rebuts the “why-bother?” myths and provides practical tips on how to more effectively help psychiatric patients stop smoking.

DEBUNKING THREE MYTHS

Mentally ill women and men consume nearly one-half (44%) of the cigarettes smoked in the United States (Table 1)^1-3 and thus are at high risk for tobacco-related premature death, cancer, cardiovascular disease, and respiratory disorders. Although recognized as a leading cause of death, cigarette smoking by psychiatric patients frequently goes unaddressed, contributing to excess mortality in this population.⁴

Table 1

Cigarette smoking: An epidemic among psychiatric patients

• psychiatrists seldom (6,7
  
• when counseling did occur, nicotine replacement therapy was not prescribed.⁶
  

Tobacco dependence is a syndrome with strong genetic and biologic roots. Family, twin, and adoption studies show consistently that tobacco dependence is genetically mediated.⁸ Genetic polymorphisms are being identified that may modify an individual’s risk for developing nicotine dependence—such as the gene encoding the cytochrome P-450 2A6 isoenzyme (CYP 2A6) that metabolizes nicotine to cotinine.⁹ Disturbed nicotinic receptor functioning has been shown in persons with schizophrenia, mood disorders, anxiety disorders, and attention-deficit/hyperactivity disorders.^3,10,11

Tobacco dependence is a chronic, relapsing condition that usually requires repeated intervention to motivate patients to try to quit and to help those who are willing to quit to succeed. Effective smoking cessation aids include:

• behavioral therapy (brief physician advice, problem-solving skills/skills training)
  
• pharmacologic therapy (nicotine replacement, sustained-release bupropion).¹²
  

Is smoking ‘self-medication’? Compelling evidence indicates that cholinergic mechanisms and nicotinic receptors (nAChRs) are involved in the pathophysiology of schizophrenia and other neuropsychiatric disorders.^3,10 Nicotine administration appears to improve sensory-processing and cognitive deficits observed in schizophrenia.^2,3 Moreover, the association between depression and smoking¹³ —and tobacco smoke’s monoamine oxidase-inhibiting and other psychoactive properties¹⁴ —have led some to posit that cigarette smoking may have antidepressant actions.¹⁰

For all these reasons, some authors have speculated that tobacco use may be a form of self-medication among the psychiatrically ill.³ The problem with this hypothesis, however, is that tobacco smoke is—at best—an untested and potentially lethal cognitive enhancer, antidepressant, or anxiolytic. Animal and human studies may find therapeutic effects of acute nicotine administration, but the cognitive effects of chronic tobacco smoking are not known.

Table 2

5 ‘A’s of brief clinical intervention for tobacco dependence

Adverse effects from quitting? Smokers with a history of major depressive disorder have been shown to be at risk to:

• develop another depressive episode after they quit smoking¹⁵
  
• experience more severe withdrawal symptoms during abstinence, compared with smokers with no history of depression.^13,16
  

Concerns that substance-abusing patients should not attempt to quit smoking during alcohol and other drug dependence treatment are also unsubstantiated. Rather than exacerbating drug addiction, smoking cessation has been found to improve addicts’ abstinence rates.¹⁹

USING AVAILABLE THERAPIES

Evidence is insufficient so far to show whether psychiatrically ill smokers would benefit more from specially tailored cessation treatments than from standard treatments, according to the 2000 U.S. Public Health Service clinical practice guide.¹² Thus, while researchers try to resolve this issue, psychiatrists are left to use medications found to be effective in smokers overall.

Clinical vignette. Mr. J, age 45, has paranoid-type schizophrenia and has been smoking at least two packs of cigarettes daily for 25 years. He complains of a productive cough and expresses interest in quitting smoking when his psychiatrist raises this topic.

His persecutory delusions are well-controlled on olanzapine, 10 mg/d. He is adhering with his medications and participating in weekly group counseling that provides supportive therapy for patients with serious mental illness.

In this schizophrenic smoker who is willing to try to quit, the psychiatrist performed the first three of “5 ‘A’s” (Table 2) of brief clinical intervention for tobacco dependence.^5,12 The next steps are to assist the patient’s effort to quit and arrange follow-up.

When to quit. The best time for a smoker with psychiatric illness to try to quit is when he or she:

• is psychiatrically stable
  
• is not in crisis
  
• has no recent or planned psychiatric drug changes.
  

Smoking cessation may increase blood levels of these psychotropics

Olanzapine’s clearance is approximately 40% higher in smokers than in nonsmokers. The psychiatrist discussed this with Mr. J and:

• asked him to call if side effects develop during the quit attempt
  
• scheduled more-frequent appointments to monitor side effects.
  

Mr. J’s schizophrenia is stable on maintenance therapy with an atypical antipsychotic. Schizophrenic smokers taking atypicals may be more able to quit smoking with NRT or sustained-release bupropion, compared with those taking conventional antipsychotics.²

The psychiatrist also determined that Mr. J had tried to quit smoking three times. Two of these attempts were done “cold turkey,” without pharmacotherapy, and one involved using nicotine gum. Mr. J said that although the gum “worked well at first,” he stopped using it because it was expensive and made his mouth sore. This information helped the psychiatrist choose medication for this quit attempt.

Most smoking cessation guidelines rely on a stepped-care approach, progressing from minimal to more-intensive interventions as needed.⁵ Mr. J’s psychiatrist devised an intensive treatment plan because:

• Mr. J has tried to quit before
  
• schizophrenic patients generally have more difficulty quitting and are more nicotine-dependent than other smokers.
  

Table 4

Nicotine replacement and other options for smoking cessation

Follow-up. Recognizing that most relapses occur in the first few days of quitting, the psychiatrist sets Mr. J’s first follow-up appointment for the day after his TQD to assess:

• whether he has smoked and number of cigarettes smoked per day
  
• presence and severity of withdrawal symptoms
  
• onset of psychiatric symptoms
  
• treatment adherence
  
• how he is handling high-risk situations and urges to smoke
  
• medication side effects.⁶
  

Related resources

• American Psychiatric Association. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry 1996; 53(153[suppl]): 1-31.
  
• Fiore MC, Bailey WC, Cohen SJ, et.al. Treating tobacco use and dependence. Clinical practice guideline. Rockville, MD: U.S. Public Health Service, 2000. http://www.ahcpr.gov/path/tobacco.htm. Accessed Dec. 13, 2004.
  

• Amantadine • Symmetrel
  
• Bupropion • Wellbutrin SR, Zyban
  
• Clonidine • Catapres
  
• Nicotine nasal spray • Nicotrol NS
  
• Nicotine polacrilex • Nicorette
  
• Nicotine replacement patch • Nicoderm CQ, Nicotrol, others
  
• Nicotine vapor inhaler • Nicotrol Inhaler
  
• Nortriptyline •Aventyl, Pamelor
  

Dr. Anthenelli receives grant/research support from Sanofi-Aventis and Ortho-McNeil Pharmaceuticals and is a consultant and speaker for Sanofi-Aventis.

Acknowledgments

The author would like to thank Reene Cantwell for technical assistance in preparing this manuscript. This work was supported by grants R01 AA13307 and R01 AA13957 from the National Institute on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs.

Three myths about cigarette smoking may explain why psychiatrists rarely intervene in their patients’ tobacco dependence:

• Cigarette smoking is an incurable habit in psychiatric patients and thus not worth the effort of intervening.
  
• Cigarette smoking is an acceptable form of self-medication in persons with psychiatric illness.
  
• Quitting smoking will worsen psychiatric symptoms.
  

Smoking by psychiatric patients is treatable, however, and evidence proves that many can quit.¹ This article rebuts the “why-bother?” myths and provides practical tips on how to more effectively help psychiatric patients stop smoking.

DEBUNKING THREE MYTHS

Mentally ill women and men consume nearly one-half (44%) of the cigarettes smoked in the United States (Table 1)^1-3 and thus are at high risk for tobacco-related premature death, cancer, cardiovascular disease, and respiratory disorders. Although recognized as a leading cause of death, cigarette smoking by psychiatric patients frequently goes unaddressed, contributing to excess mortality in this population.⁴

Table 1

Cigarette smoking: An epidemic among psychiatric patients

• psychiatrists seldom (6,7
  
• when counseling did occur, nicotine replacement therapy was not prescribed.⁶
  

Tobacco dependence is a syndrome with strong genetic and biologic roots. Family, twin, and adoption studies show consistently that tobacco dependence is genetically mediated.⁸ Genetic polymorphisms are being identified that may modify an individual’s risk for developing nicotine dependence—such as the gene encoding the cytochrome P-450 2A6 isoenzyme (CYP 2A6) that metabolizes nicotine to cotinine.⁹ Disturbed nicotinic receptor functioning has been shown in persons with schizophrenia, mood disorders, anxiety disorders, and attention-deficit/hyperactivity disorders.^3,10,11

Tobacco dependence is a chronic, relapsing condition that usually requires repeated intervention to motivate patients to try to quit and to help those who are willing to quit to succeed. Effective smoking cessation aids include:

• behavioral therapy (brief physician advice, problem-solving skills/skills training)
  
• pharmacologic therapy (nicotine replacement, sustained-release bupropion).¹²
  

Is smoking ‘self-medication’? Compelling evidence indicates that cholinergic mechanisms and nicotinic receptors (nAChRs) are involved in the pathophysiology of schizophrenia and other neuropsychiatric disorders.^3,10 Nicotine administration appears to improve sensory-processing and cognitive deficits observed in schizophrenia.^2,3 Moreover, the association between depression and smoking¹³ —and tobacco smoke’s monoamine oxidase-inhibiting and other psychoactive properties¹⁴ —have led some to posit that cigarette smoking may have antidepressant actions.¹⁰

For all these reasons, some authors have speculated that tobacco use may be a form of self-medication among the psychiatrically ill.³ The problem with this hypothesis, however, is that tobacco smoke is—at best—an untested and potentially lethal cognitive enhancer, antidepressant, or anxiolytic. Animal and human studies may find therapeutic effects of acute nicotine administration, but the cognitive effects of chronic tobacco smoking are not known.

Table 2

5 ‘A’s of brief clinical intervention for tobacco dependence

Adverse effects from quitting? Smokers with a history of major depressive disorder have been shown to be at risk to:

• develop another depressive episode after they quit smoking¹⁵
  
• experience more severe withdrawal symptoms during abstinence, compared with smokers with no history of depression.^13,16
  

Concerns that substance-abusing patients should not attempt to quit smoking during alcohol and other drug dependence treatment are also unsubstantiated. Rather than exacerbating drug addiction, smoking cessation has been found to improve addicts’ abstinence rates.¹⁹

USING AVAILABLE THERAPIES

Evidence is insufficient so far to show whether psychiatrically ill smokers would benefit more from specially tailored cessation treatments than from standard treatments, according to the 2000 U.S. Public Health Service clinical practice guide.¹² Thus, while researchers try to resolve this issue, psychiatrists are left to use medications found to be effective in smokers overall.

Clinical vignette. Mr. J, age 45, has paranoid-type schizophrenia and has been smoking at least two packs of cigarettes daily for 25 years. He complains of a productive cough and expresses interest in quitting smoking when his psychiatrist raises this topic.

His persecutory delusions are well-controlled on olanzapine, 10 mg/d. He is adhering with his medications and participating in weekly group counseling that provides supportive therapy for patients with serious mental illness.

In this schizophrenic smoker who is willing to try to quit, the psychiatrist performed the first three of “5 ‘A’s” (Table 2) of brief clinical intervention for tobacco dependence.^5,12 The next steps are to assist the patient’s effort to quit and arrange follow-up.

When to quit. The best time for a smoker with psychiatric illness to try to quit is when he or she:

• is psychiatrically stable
  
• is not in crisis
  
• has no recent or planned psychiatric drug changes.
  

Smoking cessation may increase blood levels of these psychotropics

Olanzapine’s clearance is approximately 40% higher in smokers than in nonsmokers. The psychiatrist discussed this with Mr. J and:

• asked him to call if side effects develop during the quit attempt
  
• scheduled more-frequent appointments to monitor side effects.
  

Mr. J’s schizophrenia is stable on maintenance therapy with an atypical antipsychotic. Schizophrenic smokers taking atypicals may be more able to quit smoking with NRT or sustained-release bupropion, compared with those taking conventional antipsychotics.²

The psychiatrist also determined that Mr. J had tried to quit smoking three times. Two of these attempts were done “cold turkey,” without pharmacotherapy, and one involved using nicotine gum. Mr. J said that although the gum “worked well at first,” he stopped using it because it was expensive and made his mouth sore. This information helped the psychiatrist choose medication for this quit attempt.

Most smoking cessation guidelines rely on a stepped-care approach, progressing from minimal to more-intensive interventions as needed.⁵ Mr. J’s psychiatrist devised an intensive treatment plan because:

• Mr. J has tried to quit before
  
• schizophrenic patients generally have more difficulty quitting and are more nicotine-dependent than other smokers.
  

Table 4

Nicotine replacement and other options for smoking cessation

Follow-up. Recognizing that most relapses occur in the first few days of quitting, the psychiatrist sets Mr. J’s first follow-up appointment for the day after his TQD to assess:

• whether he has smoked and number of cigarettes smoked per day
  
• presence and severity of withdrawal symptoms
  
• onset of psychiatric symptoms
  
• treatment adherence
  
• how he is handling high-risk situations and urges to smoke
  
• medication side effects.⁶
  

Related resources

• American Psychiatric Association. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry 1996; 53(153[suppl]): 1-31.
  
• Fiore MC, Bailey WC, Cohen SJ, et.al. Treating tobacco use and dependence. Clinical practice guideline. Rockville, MD: U.S. Public Health Service, 2000. http://www.ahcpr.gov/path/tobacco.htm. Accessed Dec. 13, 2004.
  

• Amantadine • Symmetrel
  
• Bupropion • Wellbutrin SR, Zyban
  
• Clonidine • Catapres
  
• Nicotine nasal spray • Nicotrol NS
  
• Nicotine polacrilex • Nicorette
  
• Nicotine replacement patch • Nicoderm CQ, Nicotrol, others
  
• Nicotine vapor inhaler • Nicotrol Inhaler
  
• Nortriptyline •Aventyl, Pamelor
  

Dr. Anthenelli receives grant/research support from Sanofi-Aventis and Ortho-McNeil Pharmaceuticals and is a consultant and speaker for Sanofi-Aventis.

Acknowledgments

The author would like to thank Reene Cantwell for technical assistance in preparing this manuscript. This work was supported by grants R01 AA13307 and R01 AA13957 from the National Institute on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs.