Mirtazapine for antipsychotic-induced acute akathisia: a systematic review and meta-analysis of randomized placebo-controlled trials

Abstract

Objective: To conduct a systematic review and meta-analysis of randomized placebo-controlled trials of mirtazapine for the treatment of antipsychotic-induced acute akathisia (AIAA).

Methods: Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as www.clinicaltrials.gov, www.controlled-trials.com, and www.clinicalstudyresults.org. The study eligibility criteria were randomized, double-blind clinical trials comparing mirtazapine with placebo for AIAA with standardized rating for akathisia as outcome measure. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (response rate and complete remission) and treatment effects were expressed as Mantel-Haenszel risk ratio (RR). Fixed-effect meta-analysis was performed as heterogeneity was not significant. Number need to treat (NNT) as a measure of relative treatment effectiveness was calculated.

Results: A systematic review of the literature revealed six studies that had assessed mirtazapine for the treatment of AIAA. Of these, two studies (n = 86) met the review inclusion criteria and were included in the final analysis. A meta-analysis was performed to see the effect size of response rate and complete remission. For response rate, RR was 6.67 [95% confidence interval (CI) 2.14-20.78], favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.001, NNT 4, 95% CI 2.6-8.6). For complete remission, RR was 6.20 (95% CI 1.74-22.08), favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.005, NNT 5, 95% CI 2.9-11.6).

Conclusions: Although limited to only two studies and small sample, existing data support the efficacy of mirtazapine for the treatment of AIAA, with one in four patients showing partial response and one in five patients showing complete remission.

Keywords: akathisia; meta-analysis; mirtazapine; systematic review.

Figure 1.

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2009 flow diagram.

Figure 2.

Forest plot showing response rate (at least two-point reduction in BAS Global Scale) in randomized controlled trials comparing mirtazapine with placebo for antipsychotic-induced acute akathisia (N = 86). CI, confidence interval; M-H, Mantel–Haenszel.

Figure 3.

Forest plot showing complete remission (0 or 1 on BAS Global Scale) in randomized controlled trials comparing mirtazapine and placebo for antipsychotic-induced acute akathisia (N = 86). CI, confidence interval; M-H, Mantel–Haenszel.