Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial
In brief
Ketamine rapidly reduces psychological pain in suicidal inpatients for up to four days
In a double-blind trial of 156 suicidal inpatients, two IV ketamine infusions lowered self-rated psychological pain scores within 40 minutes and sustained the advantage through 96 hours, whereas placebo showed no early benefit. The effect persisted after accounting for depression and hopelessness and was strongest in bipolar patients, suggesting ketamine could serve as an acute psychological-pain reliever, though longer-term impact remains unclear.
- Journal
- Journal of affective disorders (Q1)
- Published
- 10 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Ilya Baryshnikov, Christophe Demattei, Mocrane Abbar, Erkki Isometsä, Fabrice Jollant
- PMID
- 42575195
- DOI
- 10.1016/j.jad.2026.122366
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (top studies of the week, 16 August 2026).
Abstract
BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (0.9% saline) 24 h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96 h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n = 73) or placebo (n = 83). Psychological pain decreased in both groups but was lower with ketamine during the first 96 h. Pointwise scores were lower with ketamine from 40 min to 96 h, largest at 40 min, 2 h, 4 h, and 24 h (all p < 0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96 h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.