Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea

Sleep. 2008 Jun;31(6):824-31. doi: 10.1093/sleep/31.6.824.


Objective: Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials.

Methods: Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10-40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15 mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA.

Results: Two patients withdrew from Study 1 after complaints of unacceptable lethargy. Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects. No measurement of sleep apnea improved due to mirtazapine in either study. Weight gain was significantly greater on mirtazapine than on placebo in both trials.

Conclusions: Mirtazapine did not improve sleep apnea in either trial. Mirtazapine caused weight gain, which may further worsen OSA. Therefore, mirtazapine is not recommended for the treatment of OSA.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Tolerance*
  • Female
  • Histamine H1 Antagonists / therapeutic use*
  • Humans
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Mianserin / analogs & derivatives*
  • Mianserin / therapeutic use
  • Mirtazapine
  • Polysomnography
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep, REM / physiology
  • Treatment Outcome


  • Histamine H1 Antagonists
  • Hypnotics and Sedatives
  • Mianserin
  • Mirtazapine