Emerging preclinical and clinical evidence suggests a potential role of nicotinic acetylcholine receptors in the pathophysiology of depression. Several clinical trials have investigated the efficacy of nicotinic acetylcholine receptor antagonists in treatment-resistant depression. We performed this meta-analysis to investigate whether nicotinic acetylcholine receptor antagonists significantly improve symptoms in patients with major depressive disorder who have an inadequate response to standard antidepressant therapy.

A comprehensive literature search identified 6 randomized controlled trials. These 6 trials, which included 2067 participants, were pooled for this meta-analysis using a random-effects model.

Nicotinic acetylcholine receptor antagonists failed to show superior efficacy compared to placebo in terms of the mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score [mean difference=–0.12 (95% CI=–0.96 to 0.71); response rate (risk ratio [RR]=0.92 (95% CI=0.83 to 1.02)); and remission rate [RR]=1.01 (95% CI= 0.83 to 1.23)].

This meta-analysis failed to confirm preliminary positive evidence for the efficacy of nicotinic acetylcholine receptor antagonists in treatment-resistant depression. Further studies investigating the efficacy of various alternative treatment strategies for treatment-resistant depression will help clinicians to better understand and choose better treatment options for these populations.