The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis
S. Wilkinson, Elizabeth D. Ballard, Michael H. Bloch, S. Mathew, James W. Murrough, Adriana Feder, Peter Šóš, Gang Wang, Carlos A. Zarate, Gerard Sanacora
American Journal of Psychiatry October 3, 2017 DOI: 10.1176/appi.ajp.2017.17040472 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and individual participant data meta-analysis Peer reviewed |
|---|---|
| Sample size | 167 |
| Population | Depressed patients with suicidal ideation at baseline |
| Intervention | Ketamine |
| Dose | single dose |
| Duration | Up to one week post-ketamine administration |
| Topics | Esketamine Ketamine |
| Citations | 680 |
| Key findings | Ketamine rapidly reduces suicidal ideation for up to one week, with effects partially independent of mood improvement. |
Abstract
Objective: Suicide is a public health crisis with limited treatment options. We conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation.
Method: Individual participant data were obtained from 10 of 11 identified comparison intervention studies (using either saline or midazolam as control). The analysis included only participants with suicidal ideation at baseline (n=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D)) and self-reported scales (Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) or Beck Depression Inventory (BDI)), obtained for up to one week post-ketamine administration.
Results: Ketamine rapidly reduced (one day) suicidal ideation on both the clinician-administered (p<0.001) and self-reported outcome measures (p<0.001). Effect sizes were moderate-to-large (Cohen’s d=0.51–0.85) at all time points post-dose. Sensitivity analysis demonstrated that, compared to controls, ketamine had significant benefits on the individual suicide items of the MADRS, HAM-D, and QIDS-SR (all p<0.001) but not on the BDI (p=0.080). Ketamine’s effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms.
Conclusions: Ketamine rapidly reduced suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, though subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine’s long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.