Selection of the optimal dose of sertraline for depression: A dose-response meta-analysis of randomized controlled trials

Abstract

Sertraline has been shown to be effective in the treatment of depression. However, the relationship between the dosage of sertraline and its efficacy and safety are unclear. We identified RCTs that compared sertraline with placebo for the treatment of depression, conducted conventional meta-analyses on the efficacy and safety of sertraline, and assessed the nonlinear dose-response relationship between sertraline dosage and the changes in HAM-D and CGI-S scores, dropout from care for any reason or due to adverse effects, and the rate of adverse effects, using a 1-stage restricted cubic spline regression model. Twenty-one RCTs involving 4,235 patients were included. The pooled mean differences (MD) in the change in HAM-D total score [MD=-2.34, 95% confidence interval (CI) -2.93, -1.76], CGI-S score and MADRS score, but also the dropout rate for adverse effects, and rate of adverse effects were higher in sertraline group. The therapeutic response of sertraline for treating depression increased with the dosage. Meanwhile, the risk of total adverse reactions slightly decreased between 50 and 150 mg, and increased at doses above 150 mg. The dose-dependence of both efficacy and safety need to be considered when choosing the optimal dosage of sertraline.

Keywords: Depression; Dose-response relationship; Sertraline; Systematic review.