Suicide prevention in psychiatric disorders with medication: a systematic review and meta-analysis of observational studies

BackgroundPsychiatric disorders are associated with an increased risk of suicidal behaviour. The effect of pharmacological treatments on suicide-related outcomes is inconsistent. Although the main approach to evaluate effectiveness, randomised controlled trials may not provide externally valid results for suicide prevention in psychiatric populations. We aimed to synthesise the evidence and assess the medication effects on suicide outcomes from observational studies.MethodsWe systematically searched eight databases from database inception to March 2025 for pharmacoepidemiological and other observational studies on suicide-related outcomes in people treated with the main types of psychotropic medications. We included primary studies involving adults with psychiatric diagnoses who were prescribed medication and a comparison sample with the same diagnosis without prescribed medication (between-individual studies) or the same individuals during a non-prescription period (within-individual studies). We excluded studies that did not report psychiatric diagnoses and selected samples (such as inpatients only). Outcomes were any suicide-related behaviour (self-harm, attempted suicide) and suicide mortality. We pooled effect sizes as odds ratios (OR), hazard ratios (HR) or risk ratios (RR) using random-effects models and assessed study quality. The study protocol was registered with PROSPERO, CRD42024515794.FindingsWe identified 47 independent studies from 13 countries based on more than 6 million people (46.6% male). Across main diagnostic categories and 70 individual medications examined, strongest associations with suicide risks were found for second generation antipsychotics in schizophrenia spectrum disorders (OR range 0.35 to 0.75), lithium and divalproex/valproic acid in bipolar disorder (OR range 0.26 to 1.03), and SSRIs and tricyclic antidepressants in depression (OR range 0.47-0.78). Benzodiazepines were associated with higher suicide risks in all diagnostic categories (OR range 1.57-5.47). There was evidence for publication bias for SSRIs in depression, leading to more papers reporting higher risks of suicide-related outcomes.InterpretationObservational studies suggest a role for psychotropic medication for suicide prevention in certain psychiatric disorders.