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, M. Bloch, S. Mathew, J. Murrough, A. Feder, P. Šóš, Gang Wang, C. Zarate, G. Sanacora
American Journal of Psychiatry October 3, 2017 Peer reviewed DOI: 10.1176/appi.ajp.2017.17040472 via Semantic Scholar 680 citations
Summary
A single dose of ketamine rapidly reduces suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. The effect is moderate to large and partially independent of changes in depressive symptoms. The analysis combined data from 167 participants across 10 studies comparing ketamine to a placebo (saline or midazolam). Ketamine significantly improved clinician-rated and self-reported suicidal ideation, though not on one self-report measure (the Beck Depression Inventory). The authors call for further research on long-term safety and suicide risk reduction before clinical use.
Study at a glance
| Design | systematic review and individual participant data meta-analysis |
|---|---|
| Sample size | 167 |
| Population | depressed patients with suicidal ideation at baseline |
| Key finding | 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.