Pharmacokinetics

• Half life 25–41 hours

• Active metabolite

• Metabolized in part by CYP450 3A4

Drug Interactions

• Increased depressive effects when taken with other CNS depressants

• Effects of quazepam may be increased by CYP450 3A4 inhibitors such as nefazodone or fluvoxamine

Other Warnings/Precautions

• Insomnia may be a symptom of a primary disorder, rather than a primary disorder itself

• Some patients may exhibit abnormal thinking or behavioral changes similar to those caused by other CNS depressants (i.e., either depressant actions or disinhibiting actions)

• Some depressed patients may experience a worsening of suicidal ideation

• Use only with extreme caution in patients with impaired respiratory function or obstructive sleep apnea

• Quazepam should be administered only at bedtime

Do Not Use

• If patient is pregnant

• If patient has angle-closure glaucoma

• If there is a proven allergy to quazepam or any benzodiazepine

QUAZEPAM: SPECIAL POPULATIONS

Renal Impairment

• Recommended dose: 7.5 mg/day

Hepatic Impairment

• Recommended dose: 7.5 mg/day

Cardiac Impairment

• Benzodiazepines have been used to treat insomnia associated with acute myocardial infarction

Elderly

• Recommended dose: 7.5 mg/day

• If 15 mg/day is given initially, try to reduce the dose to 7.5 mg/day after the first 1–2 nights

Children and Adolescents

• Safety and efficacy have not been established

• Long-term effects of quazepam in children/adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Risk Category X [positive evidence of risk to human fetus; contraindicated for use in pregnancy]

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• Effects on infant have been observed and include feeding difficulties, sedation, and weight loss

QUAZEPAM: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Transient insomnia

Potential Disadvantages

• Chronic nightly insomnia

Primary Target Symptoms

• Time to sleep onset

• Total night sleep

• Nighttime awakening

Pearls

✽ Because quazepam tends to accumulate over time, perhaps not the best hypnotic for chronic nightly use

• If tolerance develops, it may result in increased anxiety during the day and/or increased wakefulness during the latter part of the night

• Quazepam has a longer half-life than some other sedative hypnotics, so it may be less likely to cause rebound insomnia on discontinuation

✽ Long-term accumulation of quazepam and its active metabolites may cause insidious onset of confusion or falls, especially in the elderly

• Though not systematically studied, benzodiazepines have been used effectively to treat catatonia and are the initial recommended treatment

Suggested Reading

Ankier SI, Goa KL. Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia. Drugs 1988;35:42–62.

Hilbert JM, Battista D. Quazepam and flurazepam: differential pharmacokinetic and pharmacodynamic characteristics. J Clin Psychiatry 1991;52(Suppl):S21–6.

Kales A. Quazepam: hypnotic efficacy and side effects. Pharmacotherapy 1990;10:1–10.

Kirkwood CK. Management of insomnia. J Am Pharm Assoc (Wash) 1999;39:688–96.

Roth T, Roehrs TA. A review of the safety profiles of benzodiazepine hypnotics. J Clin Psychiatry 1991;52(Suppl):S38–41.

QUETIAPINE

QUETIAPINE: THERAPEUTICS

Brands

• Seroquel

• Seroquel XR

see index for additional brand names

Generic?

Yes

Class

• Atypical antipsychotic (serotonin-dopamine antagonist; second generation antipsychotic; also a mood stabilizer)

Commonly Prescribed for

(bold for FDA approved)

• Acute schizophrenia in adults (quetiapine, quetiapine XR) and ages 13–17 (quetiapine)

• Schizophrenia maintenance (quetiapine XR)

• Acute mania in adults (quetiapine and quetiapine XR, monotherapy and adjunct to lithium or valproate) and ages 10–17 (quetiapine, monotherapy and adjunct to lithium or valproate)

• Bipolar maintenance (quetiapine, quetiapine XR)

• Bipolar depression (quetiapine, quetiapine XR)

• Depression (quetiapine XR, adjunct)

• Other psychotic disorders

• Mixed mania

• Behavioral disturbances in dementias

• Behavioral disturbances in Parkinson’s disease and Lewy body dementia

• Psychosis associated with levodopa treatment in Parkinson’s disease

• Behavioral disturbances in children and adolescents

• Disorders associated with problems with impulse control

• Severe treatment-resistant anxiety