This article is more than 5 years old. Information may no longer be current.

Higher doses of SSRIs increase efficacy, decrease tolerability for major depressive disorder

A systematic review and meta-analysis indicated higher doses of serotonin reuptake inhibitors are slightly more effective for treatment of major depressive disorder in adults, with benefit plateauing at around 250 mg of imipramine equivalents.

“While the efficacy of selective serotonin reuptake inhibitor (SSRI) medications and their widespread use is generally accepted in major depressive disorder (especially in more severe cases), there remains some uncertainty as to the optimal dose for SSRI pharmacotherapy of major depressive disorder,” Ewgeni Jakubovski, MA, of Yale Child Study Center, New Haven, Connecticut, and colleagues wrote.

To assess the relationship between dosage and treatment response in major depressive disorder (MDD), researchers conducted a systemic review and meta-analysis of 40 studies among 10,039 patients. Included studies examined efficacy of SSRIs for treating MDD in adults and assessed improvement in depression severity at multiple time points.

Longitudinal modeling and endpoint analysis indicated a small but statistically significant positive association between SSRI dose and efficacy (P = .004).

Higher doses of SSRIs were associated with an increased risk for dropouts due to side effects (P = .0028) and decreased risk for all-cause dropout (P = .011).

“Our meta-analysis provides evidence to support clinical guidelines that recommend raising SSRI dose in adults with [MDD] who do not respond to SSRI medications at or below the lower end of the therapeutic dose range,” the researchers wrote. “Higher doses of SSRIs are associated with increased efficacy (number needed to treat for treatment response range: 14-16) but also reduced tolerability as evidenced by a higher likelihood of dropouts due to side effects in trials (number needed to harm range: 22-24).” – by Amanda Oldt

Disclosure: Jakubovski reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.