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 combined raw data from ten clinical trials to see whether a single intravenous dose of ketamine quickly reduces suicidal thoughts in people with depression. They looked only at 167 people who had suicidal thoughts at the start. Compared with placebo or an active control, ketamine cut suicidal thinking within one day and the benefit lasted for about a week in many people. The effect was partly separate from general improvements in mood. The authors say more research is needed on long-term safety and whether ketamine actually lowers the risk of suicide before it can be used widely in clinics.

Key facts:

• The report pooled individual data from ten comparison trials and focused on 167 people who had suicidal thoughts before treatment.
• Participants received a single dose of ketamine given into a vein and were compared with people who got saline (salt water) or midazolam (a short-acting sedative).
• Suicidal thoughts fell rapidly after ketamine, usually within one day, and the reduction lasted for about one week for many people.
• The size of the benefit was described as moderate to large across different measurement times, meaning the change was noticeable rather than tiny.
• When researchers adjusted for overall changes in depression, ketamine’s effect on suicidal thoughts stayed statistically meaningful, suggesting it was at least partly independent from just feeling less depressed.
• One of the self-report questionnaires used (the Beck Depression Inventory) did not show a significant ketamine benefit, while three other measures did, so findings varied by the way thoughts were measured.
• The study cannot tell us about long-term safety or whether ketamine actually reduces deaths by suicide. The authors call for more trials that include different kinds of patients before clinical use is recommended.

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