Exploring the effects of pharmacological treatments on suicidality in children and adolescents: a structured review of the literature and narrative synthesis.

Background: Suicide rates have risen among young people, making it a leading cause of adolescent death worldwide. Although several pharmacological treatments have been approved in the context of definite underlying conditions, their broader efficacy in reducing suicidality remains unclear. Methods: A structured review was conducted on pharmacological treatments for suicidality in under 18s. PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to 31 July 2025. Eligible studies included patients <18 years with suicidality treated with antidepressants, mood stabilisers, or antipsychotics. Exclusion criteria were non-pharmacological interventions, non-suicidal self-injury-only studies, reviews, and grey literature. Both interventional and observational designs were considered. Four authors independently screened, extracted, and appraised data using Joanna Briggs Institute tools. The primary outcome was suicidality reduction, synthesised narratively. This study is registered with PROSPERO, CRD42024548628. Findings: Twenty-three articles out of 1747 met inclusion criteria, totalling 2235 participants. Risk of bias across studies was low-to-moderate for nearly all studies (22/23). However, the majority employed weaker study designs and targeted underlying diagnoses, with suicidality rarely assessed as a primary outcome. Esketamine (four studies, n = 211) and ketamine (four, n = 6) use in major depressive disorder induced rapid reduction of acute suicidality within 24 h. In the longer term, lithium (three, n = 923) was beneficial in reducing suicidality in youths with bipolar disorder. Sertraline, citalopram, escitalopram, fluoxetine and duloxetine (six, n = 906) yielded inconsistent results. Other agents, including valproate, lamotrigine and antipsychotics such as clozapine and quetiapine exhibited some benefit in reducing suicidality, but findings were limited to small-scale studies. Interpretation: Evidence remains scarce and heterogeneous. Esketamine and lithium appear promising for acute and chronic suicidality, respectively. Further high-quality studies investigating suicidal thoughts and behaviours as independent treatment targets are needed to guide clinical decision-making. Funding: None.