Abstract
Post-stroke depression (PSD) is a common neuropsychiatric complication that adversely affects rehabilitation outcomes, cognitive recovery, and quality of life in stroke survivors. While selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line treatment, serotonin-norepinephrine reuptake inhibitors (SNRIs) have emerged as potential alternatives with broader neurochemical targets. This systematic review aimed to compare the efficacy of SSRIs and SNRIs in the treatment and prevention of PSD. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Google Scholar in accordance with PRISMA guidelines, applying filters for English-language clinical trials. Five randomized controlled trials met the inclusion criteria and were analyzed. The findings revealed that both SSRIs and SNRIs significantly improved depressive symptoms, with escitalopram showing early and superior antidepressant effects compared to sertraline. SNRIs like duloxetine and reboxetine demonstrated added benefits in cognitive outcomes, prevention of PSD, and symptom subtype-specific efficacy, particularly in retarded depression. While the overall risk of bias was low in most studies, limitations such as small sample sizes and limited direct head-to-head comparisons were noted. These results support the clinical utility of both drug classes and emphasize the need for individualized pharmacologic strategies based on patient characteristics and symptom profiles.