title: A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia.
abstract: The antidepressant mirtazapine is an alternative to classical hypnotics, and this study investigated the efficacy and safety of esmirtazapine (Org 50081, the maleic acid salt of S-mirtazapine) in patients given a diagnosis of primary insomnia after acute (2-day) treatment. Patients aged 18 to 65 years with primary insomnia were randomized to receive placebo or 1.5-, 3.0-, or 4.5-mg esmirtazapine in a balanced 4-way crossover study; 2 sleep laboratory nights with polysomnography were separated by 5-day, single-blind placebo washout periods. Polysomnography-determined total sleep time (primary end point) and patient-reported total sleep time improved by at least 25 minutes with all 3 doses of esmirtazapine (P ≤ 0.001 vs placebo). Polysomnography-measured wake time after sleep onset (P ≤ 0.0001) and latency to persistent sleep also improved vs placebo (P ≤ 0.01, 3.0 and 4.5 mg). Patient-reported sleep quality improved with 3.0- and 4.5-mg esmirtazapine (P ≤ 0.01 and P ≤ 0.05, respectively, vs placebo). Morning alertness and contentment were not altered after esmirtazapine, and calmness increased with 4.5-mg esmirtazapine vs placebo. Evening questionnaires showed no difference in duration of daytime naps but reduced energy and ability to work/function after esmirtazapine treatment periods vs placebo (P < 0.05), although this effect was limited to the first night of each 2-night period. There were few adverse events, no serious adverse events, or clinically relevant treatment differences in vital signs, laboratory values, or electrocardiogram. Esmirtazapine doses of 1.5 to 4.5 mg/day significantly improved quantity and quality of sleep and were generally well tolerated, with no evidence of safety concerns or consistent pattern of residual effects.
authors.affiliation: From the *MSD, Oss, The Netherlands; †Henry Ford Hospital, Detroit, MI; ‡Clinilabs, Inc, New York, NY; and §Merck & Co, Inc, Kenilworth, NJ.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruwe
authors.forename: Pieta
authors.initials: P
authors.lastname: IJzerman-Boon
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Gary
authors.initials: G
authors.lastname: Zammit
authors.forename: Neely
authors.initials: N
authors.lastname: Ivgy-May
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D000078785:Mirtazapine; D017063:Outcome Assessment, Health Care; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine