An Update on Somatic Treatments for Suicide Risk

Am J Psychiatry. 2026 Jun 1;183(6):382-400. doi: 10.1176/appi.ajp.20260287. Epub 2026 Jun 1.

ABSTRACT

OBJECTIVE: Suicide is a major cause of death worldwide and a key public health challenge. Pharmacologic and neuromodulatory interventions are central to suicide prevention. This review summarizes evidence for these interventions with potential antisuicidal effects across major psychiatric disorders and, where possible, distinguishes their direct effects on suicide diathesis from those mediated by psychiatric symptom improvement.

METHODS: This scoping review synthesized evidence from randomized controlled trials (RCTs), meta-analyses, national registry studies, and large pharmacoepidemiologic and cohort studies to examine associations between pharmacologic and neuromodulatory treatments and suicide deaths, suicide attempts, or suicidal ideation as outcomes. Studies were appraised based on design, sample size, population, and outcome definitions.

RESULTS: Lithium and clozapine were associated with reductions in suicidal behavior in bipolar disorder and schizophrenia spectrum disorders, respectively, mediated by mechanisms beyond disease stabilization. Intravenous ketamine rapidly reduced suicidal ideation in RCTs, partially independent of antidepressant effects. Benefit was generally transient, and studies were not powered for suicidal behavior. Antidepressants reduced suicidal ideation primarily through improvement in depressive symptoms in RCTs that were generally underpowered to determine effects on suicidal behavior. Observational and patient-level RCT meta-analyses generally found reduced suicidal behavior risk. Opioid use disorder medications were associated with lowered suicide and overdose mortality in observational studies. Electroconvulsive therapy rapidly reduced suicidal ideation and suicide mortality, and transcranial magnetic stimulation appeared to reduce suicidal ideation primarily via antidepressant effects.

CONCLUSIONS: Somatic treatments reduce suicidal ideation and, in some cases, suicidal behavior risk, with effects mostly mediated by antidepressant or mood-stabilizing mechanisms. Clozapine and lithium may prevent suicidal behavior, and intravenous ketamine may reduce suicidal ideation through additional effects on suicide diathesis. Targeting the diathesis for suicidal behavior is a largely unexplored therapeutic strategy. Adequately powered RCTs to test somatic treatment effects on suicidal behavior are essential for evidence-based suicide prevention.

PMID:42219565 | DOI:10.1176/appi.ajp.20260287