Effect of dopamine partial agonist antipsychotics on suicide risk in persons with schizophrenia and schizoaffective disorders: A systematic review and meta-analysis.

BACKGROUND AND HYPOTHESIS: Clozapine is the only antipsychotic with protective effects against suicide in schizophrenia (SCZ). Newer dopamine partial agonist (DPA) antipsychotics have better tolerability and modulate serotonin, dopamine, and N-methyl-d-aspartate neurotransmission pathways implicated in suicide. We aim to investigate the effects of DPAs on suicide in SCZ. METHODS: We searched seven databases up to February 2026 for SCZ studies that reported suicide data. The primary outcome was suicide deaths and attempts; suicidal ideation was added as a secondary outcome. Random effects meta-analyses quantified suicide risk in randomized controlled trials (RCT) while single proportion meta-analyses assessed longitudinal suicide risk in open label extension trials (OLE). For RCTs, sensitivity analyses were conducted and subgroup analyses explored the impact of dose, drug type, and comparator arm. STUDY RESULTS: Twenty articles were included; thirteen excluded higher suicide risk participants. Compared to placebo control, DPAs did not significantly change the risk of primary [RR = 0.65, p = 0.38] or secondary [RR = 0.63, p = 0.15] suicide outcomes. Subgroup and sensitivity analyses were not statistically significant. For OLEs, there was a significant increase in the incidence of primary [Ip = 0.004, p = 0.048] and secondary [Ip = 0.024, p = 0.0013] suicide outcomes, but there was marked study heterogeneity. CONCLUSION: There is no current trial evidence to show that DPAs significantly impact suicide outcomes in SCZ. The signal from OLEs should be interpreted cautiously due to heterogeneity and requires replication. An effective clozapine alternative is needed for suicide prevention in SCZ.