Amantadine for olanzapine-induced weight gain: a systematic review and meta-analysis of randomized placebo-controlled trials

Objective: The objective of this study was to conduct a systematic review and meta-analysis of randomized placebo-controlled trials of amantadine for the treatment of olanzapine-induced weight gain. Methods: Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as ClinicalTrials. gov, Controlled-trials.com, and Clinicalstudyresults.org. Study eligibility criteria included randomized, double-blind clinical trials comparing amantadine with placebo for olanzapine-induced weight gain with body weight as an outcome measure and study duration of at least 12 weeks. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (body weight and frequency of weight loss >7%) and treatment effects were expressed as weighted mean differences (WMD) and Mantel-Haenszel odds ratio for continuous and categorical outcomes, respectively. Results: A systematic review of literature revealed six studies that had assessed amantadine for olanzapine-induced weight gain. Of these, two studies (n = 144) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight and frequency of body weight loss >7%. For body weight change, WMD was -1.85 (95% confidence interval [CI] -3.31 to -0.39) kg with amantadine as compared with placebo; the overall effect was statistically significant (p = 0.01). For frequency of body weight loss >7%, Mantel-Haenszel odds ratio for weight loss was 3.72 (95% CI 1.19-11.62), favoring amantadine as compared with placebo, and the overall effect was significant (p = 0.02). Conclusions: Existing data is limited to two studies, which support the efficacy of amantadine for olanzapine-induced weight gain and a significant proportion of patients might lose weight with amantadine compared with placebo.