ISTANBUL, TURKEY – The antidepressant trazodone showed objective polysomnographic evidence of efficacy for primary insomnia in a small double-blind, randomized trial.
This is the first objective evidence of a sleep-promoting effect for trazodone (Desyrel) in patients with primary insomnia–that is, unaccompanied by depression or anxiety, Dr. Louise M. Paterson told the annual congress of the European College of Neuropsychopharmacology.
It's an important observation, because trazodone is widely prescribed for this purpose despite the previous absence of supporting data. The drug is said to be the second most often prescribed for primary insomnia in the United States (J. Clin. Psychiatry 2005;66:469-76), though this is an off-label use for an agent licensed as an antidepressant, noted Dr. Paterson of the University of Bristol (England).
There is still an unmet clinical need for sleep-promoting agents that address poor sleep quality and treat middle insomnia–awakening in the middle of the night and difficulty falling back asleep–without causing dependence. The polysomnographic study suggests trazodone might have value toward that end.
Dr. Paterson reported on 12 adults, average age 43 years, with primary chronic insomnia of more than 1 year's duration. All had baseline normal-range anxiety and depression scores. None were on psychotropic or hypnotic medication. They were randomized double blind to 1 night of 100 mg of trazodone or placebo 2 hours before their usual bedtime, after which they underwent home polysomnography. At least 1 week later, they crossed over to the other study arm.
The 433-minute mean total sleep time on trazodone represented a 38-minute increase over placebo. The mean 129 minutes spent in slow wave sleep during the trazodone night was 33 minutes longer than with placebo. Time spent awake after sleep onset decreased from 77 minutes on placebo to 57 minutes on trazodone.
Trazodone also significantly reduced the number of awakenings while decreasing spindle density, with no change in REM sleep, overall sleep efficiency, or sleep onset, compared with placebo.
Results on the Leeds Sleep Evaluation Questionnaire and the St. Mary's Hospital Sleep Questionnaire showed significant improvements in subjective sleep factors (quality, satisfaction), compared with placebo. Yet there was no difference between trazodone and placebo in terms of “awakening from sleep” or “behavior following awake,” indicating the drug was not associated with a significant morning hangover effect, said Dr. Paterson.
There were 11 adverse events associated with the single dose of trazodone, compared with 3 with placebo. In patients on trazodone, two complained of dizziness; one had a fall; and one each reported clumsiness, nausea, attentional disturbance, or “feeling abnormal.” No one had any such complaints while on placebo.
The Avon and Wiltshire Mental Health Partnership NHS Trust funded the study. Dr. Paterson reported no financial conflicts of interest.