Safety of long-term zolpidem treatment in patients with insomnia

Because a substantial number of patients with insomnia take hypnotics for extended periods, maintenance of effectiveness and the effects of withdrawal following long-term use are critical issues. In this multicenter, single-blind study, patients between 18 and 60 years of age (mean, 42 years) received placebo for 4 to 7 nights, followed by 12 weeks of nightly treatment with zolpidem 15 mg, followed by placebo for 1 withdrawal week. If adverse events occurred, the study design allowed for a dose reduction to 10 mg. Efficacy was evaluated subjectively using the Clinical Global Impression scale at the end of the placebo run-in period and at the end of weeks 2, 4, 8, and 12 and placebo week 13. In addition, patients completed self-reports, describing their sleep before each visit. Of the 229 patients who received zolpidem, 155 patients completed all 12 weeks of treatment. Thirty-three patients had their dose decreased from 15 mg to 10 mg at some time during the study. Adverse effects led to withdrawal in only 8% of the patients initially enrolled. The incidence of side effects was considerably higher with the 15-mg dose compared with the 10-mg dose. Despite the prolonged use of higher than currently recommended doses of zolpidem, no evidence of rebound insomnia was reported. In addition, there was no evidence of drug tolerance throughout the 12 weeks of drug administration. In agreement with recommendations of numerous previous studies, the 10-mg dose was found to be safe during the 12-week treatment period.