title: Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial.
abstract: OBJECTIVE
  Esmirtazapine (Org 50081), a medication that binds with high affinity to serotonin 5-HT2A and histamine-1 receptors, was evaluated as a potential treatment for insomnia.
  
  
  METHODS
  Adults with primary insomnia were treated with esmirtazapine (3.0 or 4.5 mg) or placebo in this 6-week, double-blind, randomized, polysomnography (PSG) study. The end points included wake time after sleep onset (WASO) (primary), latency to persistent sleep, and total sleep time. Patient-reported parameters were also evaluated, including sleep quality and satisfaction with sleep duration. Residual daytime effects and rebound insomnia (sleep parameters during the single-blind placebo run-out week after treatment ended) were also assessed.
  
  
  RESULTS
  Overall, 419 patients were randomized and 366 (87%) completed treatment. The median decrease in PSG WASO (double-blind average) was 20.5 min for placebo, and 52.0 min and 53.6 min for the 3.0- and 4.5-mg esmirtazapine groups, respectively (P < 0.0001 vs. placebo for both doses). Changes in the other PSG parameters and in all patient-reported parameters were also statistically significant with both doses versus placebo. Overall, 35-42% of esmirtazapine-treated patients had adverse events (AEs) versus 29% in the placebo group. AEs were mild or moderate in most esmirtazapine-treated patients. Furthermore, the incidence of AEs leading to discontinuation was low (<8%).
  
  
  CONCLUSIONS
  Six weeks of treatment with esmirtazapine was associated with consistent improvements in objective and patient-reported parameters of sleep onset, maintenance, and duration. It was generally well tolerated, and residual daytime effects were minimal and no rebound insomnia was observed.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: mayneely@gmail.com.
authors.forename: Neely
authors.initials: N
authors.lastname: Ivgy-May
authors.affiliation: MSD, Oss, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruwe
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Krystal
authors.affiliation: Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D017060:Patient Satisfaction; D017286:Polysomnography; D012008:Recurrence; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; D008803:Mianserin; D000078785:Mirtazapine
keywords: Clinical trial; Esmirtazapine; Insomnia; Polysomnography; Sleep maintenance