Antidepressants and Body Weight: A Comprehensive Review and Meta-Analysis

Objective: Psychotropic drugs often induce weight gain, leading to discomfort and discontinuation of treatment and, more importantly, increasing the risk of obesity-related illnesses such as diabetes mellitus, hypertension, and coronary heart disease. There is evidence that antidepressant drugs may induce a variable amount of weight gain, but results are sparse and often contradictory.

Data Sources: We performed a literature search using the MEDLINE, ISI Web of Knowledge, and Cochrane research databases for all publications available to January 2009. We used the following keywords: antidepressant, psychotropic drugs, body weight, weight gain, obesity, overweight, adverse event, side effects, SSRIs, tricyclic antidepressants, and the name of each antidepressant active compound together with body weight or other keywords. Studies reporting body weight changes during treatment with different antidepressants were selected for eligibility. Finally, 116 studies were included in the analysis.

Data Extraction: Weight change mean and standard deviation and size of each group were recorded. Missing means and standard deviations were directly calculated by using information available in the article when possible. Non-placebo-controlled studies were compared to a virtual placebo sample, whose mean and standard deviation were derived by the weighted mean of means and standard deviations of all placebo samples. Methodological quality of studies, heterogeneity, publication bias, and effect of treatment duration were systematically controlled.

Data Synthesis: Quantitative results evidenced that amitriptyline, mirtazapine, and paroxetine were associated with a greater risk of weight gain. In contrast, some weight loss occurs with fluoxetine and bupropion, although the effect of fluoxetine appears to be limited to the acute phase of treatment. Other compounds have no transient or negligible effect on body weight in the short term. However, the effect of each antidepressant may vary greatly depending on an individual’s characteristics and generally became more evident in the long term to a variable degree across compounds.

Conclusions: Despite the fact that some analyses were done on only a few studies due to the difficulty of finding reliable information in literature, to our knowledge, this is the first comprehensive meta-analysis to allow comparison of different antidepressants as regards their impact on body weight. Data presented may be helpful for a more accurate treatment selection in patients at risk of obesity or related medical illness.

J Clin Psychiatry 2010;71(10):1259-1272

Submitted: May 12, 2009; accepted September 16, 2009

(doi:10.4088/JCP.09r05346blu).

Corresponding author: Alessandro Serretti, MD, PhD, Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy (alessandro.serretti@unibo.it).