Two Randomized Placebo-Controlled Trials to Evaluate the Efficacy and Tolerability of Mirtazapine for the Treatment of Obstructive Sleep Apnea

Abstract

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.

Pharmacological approaches to the treatment of obstructive sleep apnoea

“…These results are in contrast to those recently published by Marshall and co-workers, who performed two randomised placebo-controlled trials on the effects of different doses of mirtazapine on OSA severity [42]. The first study was a three-way crossover dose-finding study (7.5, 15, 30 and 45 mg of mirtazapine or placebo) for 2 weeks at each dose.…”

“…Eighteen OSA patients completed the protocol; of these, 8 received placebo while 13 received 7.5 mg, 12 received 15 mg, 11 received 30 mg and 10 received 45 mg of mirtazapine. Mirtazapine did not improve OSA severity with any dose; in fact, a small increase in AHI was observed with 15 and 30 mg of mirtazapine [42]. In the second study (parallel-group design), 26 patients were randomised to 15 mg of mirtazapine and 13 to placebo; there was no significant change in AHI after 4 weeks of treatment with mirtazapine.…”

α2-Adrenergic blockade rescues hypoglossal motor defense against obstructive sleep apnea

“…In a previous randomized double-blind controlled clinical study, the antidepressant mirtazapine (a mixed antagonist for serotonin 5HT 2 /5HT 3 receptors, histamine H 1 receptor, and α 2A /α 2C adrenoceptors; see Supplemental Table 1) was proposed to be efficacious for adult patients with OSA mainly through its antagonism of 5HT 2 /5HT 3 receptors, an effect that was thought to promote serotonin release in the brain (16). However, a subsequent trial failed to verify the suggested benefits of mirtazapine, especially at higher doses (17). The discrepancy may be explained in part by the inverse dose-dependent effects of mirtazapine on GG activity, indicating possible within-drug interaction (60).…”

“…However, related preclinical and clinical studies to date have been disappointing (8)(9)(10). Moreover, many candidate drugs have side effects such as drowsiness, weight gain, and suppression of REM sleep, which are counterproductive for OSA (14)(15)(16)(17). Other drugs that target certain inhibitory receptors (such as muscarinic receptors) on HMs have well-known cardiovascular liabilities (18).…”

New and Unconventional Treatments for Obstructive Sleep Apnea

“…Mirtazapine caused weight gain and lethargy in their trials. Therefore, mirtazapine is not recommended for the treatment of OSA [19,20].…”