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To what extent do high doses of selective serotonin reuptake inhibitors (SSRIs) confer benefits for treating depression? Some research studies and meta-analyses have indicated advantages of higher doses, and others have not. For a pairwise meta-analysis and network meta-analysis, researchers identified 33 randomized clinical trials (from 5333 articles screened) that assessed two or more fixed SSRI doses, given for ≥3 weeks for major depressive disorder (MDD).
The included studies did not examine secondary depression (e.g., in Parkinson disease) or stepwise dose increases; about two thirds of studies excluded patients with bipolar disorder. The SSRIs examined were fluoxetine (n=7 studies), citalopram (n=7), sertraline (n=6), paroxetine (n=6),…