Abstract
INTRODUCTION: Suicide risk is markedly elevated following presentation after self-harm, yet the evidence base for interventions initiated in the immediate post-presentation period has not been synthesized with specific attention to this high-risk window. Clarifying which early interventions may reduce adverse outcomes is essential for informing psychiatric care and prevention strategies. METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials enrolling individuals presenting to clinical services after self-harm, with interventions initiated within 1 month of the index episode. PubMed, Embase, PsycINFO, the WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov were searched from inception through April 24, 2025. Two reviewers independently screened studies and extracted data using standardized forms. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated with GRADE. Random-effects meta-analyses with Hartung-Knapp adjustment were conducted for intervention categories with at least three trials, and prediction intervals were calculated. Prespecified meta-regressions examined participant- and intervention-level moderators. RESULTS: Sixty randomized clinical trials, including 22,654 participants, met the inclusion criteria. Across pooled analyses, no intervention category was associated with a statistically significant reduction in repeat self-harm at any follow-up interval. For suicide deaths, problem-solving therapy was associated with lower mortality at medium-term follow-up (6-12 months; OR 0.45, 95% CI 0.29-0.70; I (2) = 0%), and brief intervention and contact was associated with lower mortality at long-term follow-up (> 12 months; OR 0.34, 95% CI 0.15-0.79; I (2) = 0%). Meta-regression analyses indicated that younger mean sample age and trial inclusion based on suicidal intent moderated effects on repeat self-harm at > 6-12 months. CONCLUSIONS: Among trials initiating treatment within 1 month of self-harm presentation, effects on repeat self-harm were small and not statistically significant, likely reflecting outcome heterogeneity in the acute post-presentation period. In contrast, structured problem-solving and brief contact-based interventions were associated with lower suicide mortality at medium- and long-term follow-up. These findings support the use of scalable early interventions in psychiatric services and highlight priorities for future trials powered to detect effects on suicide mortality. TRIAL REGISTRATION: PROSPERO: CRD42023458233.