A meta-analysis of sleep changes associated with placebo in hypnotic clinical trials.

Objectives: The effects associated with placebo (EAP) have been incompletely described in clinical trials of insomnia treatment. We conducted a meta-analysis of insomnia medication trials for the purpose of estimating the magnitude of sleep EAP.

Method: We reviewed Medline for 1966 through 2000 for the meta-analysis. The subject heading of insomnia restricted to the subheading of drug therapy was crossed against the results of a search on the subjects heading placebo and text word placebo. We selected only papers that examined primary insomnia, incorporating both placebo and active medication therapies in a randomized, double-blind, parallel-group design. We required that results be reported for 1, 2, 3, or 4 weeks of treatment, and that outcomes be reported in hours/minutes.

Results: Five papers satisfied our requirements for eligibility, comprising 213 patients receiving placebo for a 2-week interval. Subjective sleep latency demonstrated a significant reduction (mean+/-S.E.) of 13.1+/-2.0 min (95% confidence interval (CI) 9.2, 17.0) for the placebo group after combining the data across studies. Subjective total sleep time demonstrated a significant increase of 13.5+/-5.4 min (95% CI 2.9, 24.0). Polysomnographic (PSG) sleep latency demonstrated a non-significant reduction of 2.5+/-4.3 min (95% CI -5.9, 10.9).

Conclusions: The confirmation of EAP in insomnia clinical trials argues for the retention of a placebo control in future insomnia clinical trials.