Drug treatment of primary insomnia: a meta-analysis of polysomnographic randomized controlled trials.

CONTEXT: 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.

OBJECTIVE: 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.

DATA SOURCES: 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.

ELIGIBILITY CRITERIA: Only polysomnographic, parallel-group, randomized controlled drug trials were included; eligibility was determined by two independent authors.

DATA SYNTHESIS: We used a random effects model, based on 31 studies reporting 80 treatment conditions, covering 3,820 participants.

RESULTS: 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.

LIMITATIONS: Data on drug safety were not analyzed.

CONCLUSIONS: 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.