Effectiveness of Pharmacologic Interventions in the Management of Weight Gain in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis.

Objective: To collate and analyze randomized controlled trials (RCTs) that evaluated pharmacologic interventions to reduce weight gain in patients with severe mental illness (SMI).

Data Sources: Searches were conducted in PubMed, Web of Science, and PsycINFO databases from inception through May 9, 2019, using the terms ("severe mental disease" OR "severe mental illness" OR "severe mental disorder" OR schizophre* OR bipolar OR antipsychotic*) AND (weight) AND (pharmacologic* OR treatment). There was no language restriction, and the electronic search was complemented by a manual search for additional articles in reference lists and previous reviews.

Study Selection: Fifty-two studies investigating different pharmacologic weight loss interventions in SMI were retrieved. Only RCTs assessing pharmacologic interventions to manage weight gain in adult subjects with SMI and reporting change in body weight as a primary outcome were included.

Data Extraction: Two reviewers independently extracted data about the name and dose of the pharmacologic agent used to manage weight gain, trial duration, agent used for index disease, psychiatric diagnostics, and the mean change in body weight over the course of the trial. A meta-analysis was performed using a random effects model to pool mean body weight change over the course of the trial.

Results: The most-studied agent was metformin (14 studies), followed by topiramate (6 studies), nizatidine (4 studies), and sibutramine (3 studies). Other agents were investigated in 1 or 2 isolated studies. A meta-analytical procedure showed a significant pooled mean difference of -3.27 kg (95% CI, -4.49 to -2.06) for metformin compared with placebo and -5.33 kg (95% CI, -7.20 to -3.46) favoring topiramate.

Conclusions: Metformin and topiramate were the most-studied agents for weight control in SMI and were considered efficacious and safe in promoting weight reduction compared to placebo in this population. More studies are required with larger sample sizes and in line with the recommendations from research from the obesity and metabolic field to better define guidelines for use of pharmacologic interventions to reduce weight gain in patients with SMI.