Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: A randomized, double-blind placebo-controlled study and open-label extension

Abstract

Study Objectives: Esmirtazapine (1.5-4.5 mg) has demonstrated short-term sleep-promoting effects in nonelderly outpatients with chronic insomnia. This phase 3, randomized, double-blind study (NCT00631657) and its open-label extension (NCT00750919) investigated efficacy and safety of long-term esmirtazapine treatment in adult outpatients with chronic insomnia. Methods: Participants were randomized to receive esmirtazapine 4.5 mg or placebo for 6 months; those receiving esmirtazapine were then rerandomized to esmirtazapine or placebo for an additional 7 days. Participants could enter the 6-month open-label extension with esmirtazapine 4.5 mg. The primary objective of the double-blind study was to assess long-term efficacy of esmirtazapine vs placebo on self-reported total sleep time. Assessing long-term safety and tolerability were secondary and primary objectives of the double-blind and extension studies, respectively. Results: Overall, 457 participants received treatment in the double-blind study (esmirtazapine, n = 342; placebo, n = 115) and 184 participants (prior esmirtazapine, n = 136; prior placebo, n = 48) received esmirtazapine in the extension. In the double-blind study, a 48.7-minute increase in average nightly total sleep time was observed for esmirtazapine vs placebo (95% confidence interval, 35.0-62.5; P