Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a 2-week randomized outpatient trial

Background: Esmirtazapine (Org 50081), a high-affinity antagonist at 5-HT2A and H1 receptors, was assessed for its hypnotic efficacy. Methods: In this double-blind, randomized study, non-elderly patients with primary insomnia (but otherwise healthy) were treated with esmirtazapine (1.5, 3.0, or 4.5 mg) or placebo for two weeks. The primary end point was patient-reported total sleep time (TST); other patient-reported end points included sleep latency (SL), wake time after sleep onset (WASO), number of awakenings, sleep quality, and satisfaction with sleep duration. Measures to assess the potential adverse effects of treatment included morning alertness, daytime function/napping, and rebound insomnia during a single-blind placebo run-out week after treatment ended. Adverse events (AEs) were also assessed. Results: Overall, 526 patients were randomized and 463 (88%) completed treatment. All esmirtazapine doses significantly improved TST, SL, sleep quality, and satisfaction with sleep duration versus placebo. Relative to placebo, TST was increased by 30-40 min and SL decreased by similar to 12 min for all doses. The highest dose (4.5 mg) also significantly reduced WASO and number of awakenings. Across doses, AEs occurred in 25.5-32.8% of patients, compared with 20.7% with placebo. The most common AE was somnolence (similar to 10% for esmirtazapine and 2% for placebo). The incidence of AEs leading to discontinuation was low (<= 7%), and there were no serious drug-related AEs. Finally, there was no evidence of a rebound insomnia after discontinuation of esmirtazapine. Conclusions: Two weeks of treatment with esmirtazapine consistently and significantly improved patient-reported sleep parameters, and it was well tolerated in patients with primary insomnia. (C) 2015 Published by Elsevier B.V.