April 2010

Depression during Pregnancy
New guidelines aid clinicians in treating pregnant women with depression.

SSRIs versus an SNRI
A new study failed to find enhanced benefit from duloxetine (Cymbalta) compared with generic selective serotonin reuptake inhibitors in patients with depression.

Zopiclone and Morning-After Impairment
In a small trial of older adults, driving ability and cognitive performance were impaired the morning after subjects took a dose of zopiclone at bedtime.

In Brief
Antipsychotic Polypharmacy Does Not Increase Mortality Risk in Schizophrenia; Tarenflurbil Fails to Slow Cognitive Decline in Alzheimer’s Disease

Second-Generation Antipsychotics Cause Weight Gain and Adverse Metabolic Effects in Young Patients
Second-generation antipsychotics can be life-saving for youth with serious psychiatric illnesses, but they carry the risk for weight gain and possible long-term cardiovascular and metabolic problems.

Zopiclone and Morning-After Impairment

April 2010

As we reported last month (BTP 2010;33:11-12), many people take medications, prescribed and over-the-counter, hoping to combat insomnia. Although cognitive behavioral therapy may be the best long-term treatment for chronic insomnia, hypnotic medications can provide modest benefits in enhancing sleep, especially acutely. Their "downside" is that they may cause cognitive, motor, and behavioral impairment during the night and on the following morning.

Among the most commonly prescribed hypnotics are the benzodiazepine temazepam (Restoril and others) and the nonbenzodiazepine zopiclone.* Temazepam, 20 mg at bedtime, does not appear to impair a person's ability to drive a car safely the morning after.1 However, the studies on which this conclusion is based involved healthy young volunteers, whereas most hypnotic users are older adults. Zopiclone, 7.5 mg, moderately impairs morning-after driving.

The effects of sedating medications are apt to be more profound in older people, note Leufkens and Vermeeren.1 Age-related reductions in liver capacity and lean body mass can increase blood levels. In addition, older people may have increased pharmacodynamic sensitivities and often suffer cognitive and motor effects they did not experience when they were younger.

With funding from their university, Leufkens and Vermeeren studied 10 female and 8 male drivers, aged 55 to 75 years.1 In a double-blind, three-way crossover design, subjects took single oral doses of temazepam, 20 mg; zopiclone, 7.5 mg; or placebo at bedtime in random order. Ten to eleven hours after they took the "sleeping pills," subjects performed a standardized highway driving test. Before and after the driving test, their cognitive performance was assessed.

Subjects' performances on the driving test were the same after taking temazepam as they were after taking placebo. Zopiclone, however, significantly impaired driving ability (P < .002). Laboratory test results were consistent with those from the highway tests.

Morning-after impairment with hypnotics should always be a concern. Driving is risky in any case, and the risk can increase for older drivers. Based on their pharmacokinetic and pharmacodynamic properties, some hypnotics are likely to impair morning-after driving more than others. In this test in a relatively small sample of older people, temazepam, 20 mg daily, appeared comparatively safe. By contrast, zopiclone, 7.5 mg, impaired driving ability, at least through 11 hours after the dose. It is unclear if the same result would be found with eszopiclone, but it is wise to err on the side of caution.

*Racemic zopiclone is not available in the United States. However, the stereoisoform, eszopiclone, is now available as Lunesta.

1Leufkens TR, Vermeeren A: Highway driving in the elderly the morning after bedtime use of hynotics. A comparison between temazepam 20 mg, zopiclone 7.5 mg, and placebo. J Clin Psychopharmacol 2009;29:432-438.