OBJECTIVES: Given the high incidence of post-stroke depression (PSD), its serious sequalae, and inherent problems with diagnosis, prophylactic use of antidepressants may be a viable management strategy in patients experiencing stroke. The purpose of this study was to assess the prophylactic effects of antidepressants in non-depressed patients with stroke. METHODS: A meta-analysis of randomized placebo-controlled trials (RCTs) evaluating the prophylactic effects of antidepressants in non-depressed patients with stroke was conducted. Literature searches in MEDLINE, PubMed, CINAHL, PsycINFO, EMBASE, Cochrane library, and CNKI from 1950 to August 2006 were used to identify the relevant studies. Outcome measures included the occurrence rate of newly developed PSD cases and severity of depressive symptoms as indicated by mean depression rating scales scores. The effect size was presented as rate difference (RD) or weighted mean difference (WMD). RESULTS: From 10 RCTs, a total of 703 non-depressed patients after stroke were identified. The pooled occurrence rate of newly developed PSD cases in the intervention and control groups were 12.54% (41/327) and 29.17% (91/312), respectively (pooled RD=-0.17, 95% CI: -0.26 to -0.08). Prophylactic effects of antidepressants were not related to duration of use (coefficient of Pearson' correlation [ã] =0.57, p=0.11). CONCLUSION: Antidepressant prophylaxis is associated with a significant reduction in the occurrence rate of newly developed PSD, suggesting antidepressants may be considered along with other vascular preventive strategies in management of stroke patients.