Drug Treatment of Primary Insomnia: A Meta-Analysis of Polysomnographic Randomized Controlled Trials

Although insomnia is a frequent health complaint that is often treated with drugs, little is known about differences in treatment efficacy of various drug classes on objective versus subjective outcome measures. Our aim was to compare treatment efficacy of classical benzodiazepines, benzodiazepine receptor agonists (zopiclone, zolpidem and zaleplon), antidepressants (including low-dose doxepin), neuropeptides, progesterone receptor antagonists, hormones, melatonin receptor agonists, antihistamines, antiepileptics, and narcotics addressing primary insomnia. We conducted a comprehensive literature search (up to 5 April 2013) using PubMed, Cochrane Clinical Trials, PQDT OPEN, OpenGREY, ISI Web of Knowledge, PsycINFO, PSYNDEX, and the WHO International Clinical Trials Registry Platform. Only polysomnographic, parallel-group, randomized controlled drug trials were included; eligibility was determined by two independent authors. We used a random effects model, based on 31 studies reporting 80 treatment conditions, covering 3,820 participants. Effect size estimates for the total sample of pooled drug classes suggest that there is a small-to-moderate, significant, and robust effect for objective outcomes (sleep onset latency g = -0.36, total sleep time g = 0.27) and subjective outcomes (sleep onset latency g = -0.24, total sleep time g = 0.21). Results indicate higher effect sizes for benzodiazepine receptor agonists and classical benzodiazepines compared with antidepressants (including low-dose doxepin) and for classical benzodiazepines compared with benzodiazepine receptor agonists. Benzodiazepine receptor agonists demonstrated higher effect sizes for objective outcomes. Data on drug safety were not analyzed. Future studies should use objective and subjective assessment. Focusing on efficacy, clinicians should favor benzodiazepine receptor agonists and classical benzodiazepines over antidepressants (including low-dose doxepin) for primary insomnia treatment, but the additional consideration of different side effect profiles can lead to alternative treatment decisions.