BACKGROUND: Traumatic brain injury (TBI) poses a considerable risk to human health. After TBI, individuals are susceptible to a range of psychiatric disorders, with depression being a primary complication. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression
however, their efficacy in addressing major depressive disorder (MDD) in adults following TBI remains uncertain. AIM: To investigate the efficacy of SSRIs in the treatment of MDD after TBI. METHODS: A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, encompassing studies published until May 2024. This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI. Studies were assessed based sample size, treatment duration, treatment methodologies, severity of brain injury, assessment techniques, and drug response. A random-effects model was used to derive the summary effect size. RESULTS: Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment. The eight studies did not exhibit heterogeneity ( CONCLUSION: SSRIs may be effective in treating patients with MDD after TBI. Adequately powered, randomized, controlled trials are required to confirm these findings.