Early Response to Ketamine for Suicidal Crisis Reduces Suicidal Events at 3 Months

Background: Intravenous (IV) ketamine has demonstrated rapid reduction of suicidal ideation (SI), but its impact on suicidal attempts remains unclear. This study investigates the effect of IV ketamine on SI at 7 days and suicidal events (suicide attempt or hospitalizations for SI) at 3 months in a real-world clinical setting.

Methods: We conducted an observational retrospective study including 100 adult French patients who received 1 or 2 IV ketamine infusions (0.5 mg/kg) within 1 week for a suicidal crisis between June 2022 and June 2024. Depressive symptoms (Montgomery-Asberg Depression Rating Scale) and SI severity (Columbia-Suicide Severity Rating Scale [C-SSRS]) were assessed at baseline and 7 days postinfusion. Suicidal events were collected from clinical records at 3 months.

Results: Ketamine significantly reduced depressive symptoms (β = -11; P < .001) and SI severity (β = -2.0; P < .001) at 7 days after controlling for age, sex, and number of infusions. A direct (β = -0.78; P < .001) and indirect effect (β = -0.29; P = .007) on SI through depression reduction was observed. Sixty-one percent of patients were SI responders (≥50% reduction in C-SSRS severity). SI responders at 7 days had 75% lower odds of experiencing suicidal events at 3 months (OR =0.25; P = .009).

Conclusion: This is the first study demonstrating that early SI response to IV ketamine is associated with a reduced risk of suicidal events at 3 months. These findings support ketamine's unique antisuicidal properties beyond its antidepressant effects, highlighting its potential role in suicide prevention.

Trial Registration: ClinicalTrials.gov identifier: NCT06806475.