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

Author(s): Marshall NS, Yee BJ, Desai AV, Buchanan PR, Wong KK, Crompton R, Melehan KL, Zack N, Rao SG, Gendreau RM, Kranzler J, Grunstein RR

Affiliation(s): NHMRC Centre for Sleep Medicine, Woolcock Institute of Medical Research, University of Sydney, NSW Australia.

Publication date & source: 2008-06-01, Sleep., 31(6):824-31.

Publication type: Research Support, Non-U.S. Gov't

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 Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects.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.