The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Summary & key facts

Researchers gathered raw data from ten studies that tested a single intravenous dose of ketamine against a placebo or a sedative in people who were depressed and had suicidal thoughts. They analyzed data from 167 people who had suicidal thinking at the start. Ketamine cut suicidal thoughts quickly, within a day, and the drop lasted up to a week on most measures. The drop in suicidal thinking was partly separate from overall mood improvement. The authors say more work is needed on long-term safety and on whether ketamine actually reduces suicide risk before it is used widely for this purpose.

Key facts:

• The analysis combined individual-level data from ten comparison studies that used either saline or midazolam as a control.
• The pooled sample included 167 people who had suicidal thoughts before treatment.
• A single intravenous dose of ketamine reduced suicidal thinking within one day and the reduction lasted up to one week on most clinician-rated and self-report measures.
• The size of the ketamine effect was moderate to large, meaning the change was noticeable compared with control treatments.
• Ketamine's benefit on suicidal thinking remained even after taking into account changes in overall depression severity, suggesting some effect was independent of mood improvements.
• One common self-report questionnaire, the Beck Depression Inventory, did not show a significant ketamine benefit on its suicide item, so not all measures agreed.
• The authors warned that long-term safety and whether ketamine lowers actual suicide risk were not established, and more research is needed before clinical use for this purpose.

Abstract

OBJECTIVE: Suicide is a public health crisis with limited treatment options. The authors 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 that used either saline or midazolam as a control treatment. The analysis included only participants who had 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 (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. RESULTS: Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. 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 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although 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.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Suicide and Self-Harm Studies Treatment of Major Depression

Categories

Health Sciences Medicine Pharmacology

Tags

Clinical psychology Internal medicine Ketamine Medical emergency Medicine Meta-analysis Poison control Psychiatry Psychology Suicidal ideation Suicide prevention

Substances

Ketamine

Conditions & symptoms

Depression Sadness or low mood