Depression is one of the largest contributors of non-fatal health loss across the globe. Second-gen antidepressants and Selective serotonin reuptake inhibitors (SSRIs) are used as the primary line of treatment, but their optimal dosage is still in question. The objective of this study is to determine the ideal dose of SSRIs and antidepressants in patients with major depression.

This is a systematic review and dose-response meta-analysis of double-blind, randomized, controlled trials. The study included the examination of fixed dosages of five SSRIs: escitalopram, fluoxetine, paroxetine, citalopram, and sertraline; and two antidepressants: venlafaxine or mirtazapine. A total of 28,554 records were identified, out of which 77 studies, including 19,364 participants with major depression, who were given either SSRIs or antidepressants, were considered. The primary outcome of the study was the efficacy, tolerability, and acceptability of the treatments. 

For the SSRI group, the dose-efficacy curve showed an increase up to doses between 20 and 40 mg, followed by a decrease up to 80 mg. In the case of antidepressants, the dose-efficacy curve showed a gradual increase up to doses around 75-150 mg.

The research concluded that the lower range of doses of second-gen antidepressants and SSRIs achieve an optimal balance between efficacy and acceptability.