A MULTICENTER, PLACEBO-CONTROLLED STUDY EVALUATING ZOLPIDEM IN THE TREATMENT OF CHRONIC INSOMNIA

Background: Zolpidem is a short-acting, nonbenzodiazepine hypnotic wit h rapid onset of action. Even though it is not a benzodiazepine. it bi nds to one of three types of central benzodiazepine receptors, showing selective binding to the type 1 benzodiazepine receptor subtype. Ther apeutic hypnotic dosages do not disturb normal sleep patterns (sleep a rchitecture). Method: A randomized, double-blind, placebo-controlled, parallel group multicenter trial was conducted to determine the effect iveness of 10 mg and 15 mg of zolpidem in the long-term (35 nights) tr eatment of chronic insomnia in 75 patients. Sleep stage effects and mo tor and cognitive effects during the 35-night treatment period and the 3-night posttreatment period were also investigated. Results: Within the first week of treatment, 10 mg of zolpidem had a significant effec t on latency to persistent sleep and sleep efficiency. Efficacy was ma intained throughout the 35 nights of drug administration. There was no evidence of residual effect with 10 mg of zolpidem. Stage 3-4 sleep w as preserved at both the 10-mg and 15-mg zolpidem dosages. There was n o evidence of tolerance at either dose and no significant treatment di fferences between the 10-mg zolpidem group and placebo in latency to p ersistent sleep or sleep efficiency during the posttreatment period. A lso, the 10-mg zolpidem dosage was judged by the patients to have help ed them fall asleep. Similar results were observed with the 15-mg zolp idem dosage. However, there were significant decreases in REM sleep at Weeks 3 and 4 with 15 mg of zolpidem compared with placebo. Overall, incidence rates of treatment-emergent adverse events in the zolpidem g roups were similar to those in the placebo group. Conclusion: This is the first sleep laboratory study using a parallel placebo group to dem onstrate efficacy for longer than 4 weeks with a hypnotic agent. In th is study 10 mg of zolpidem was found to be safe and effective for the long-term treatment of chronic insomnia, demonstrating hypnotic effica cy without affecting sleep stages or producing tolerance effects, rebo und effects. or detrimental effects on psychomotor performance. The 15 -mg zolpidem dosage provided no clinical advantage over the 10-mg zolp idem dosage.