In this post, I link to and excerpt “Ketamine For Suicidal Ideation” from Emergency Medicine Cases’ Ep 171 Posterior Stroke, EP Lead, HEAR Score, Ketamine for Suicidal Ideation, Peer Support Workers – Highlights from Calgary EM Hodsman Lecture Day, July, 2022.
Helman, A. Lang, E. Betzner, M. McRae, A. Lin, K. VandenBerg, S. Ross, M. Borgundvaag, B. Bradshaw, C. Posterior Stroke, EP Lead, HEAR Score, Ketamine for Suicidal Ideation, Peer Support Workers- Highlights from Calgary EM Hodsman Lecture Day. Emergency Medicine Cases. July, 2022. https://emergencymedicinecases.com/posterior-stroke-ep-lead-hear-score-ketamine-for-suicidal-ideation-peer-support-highlights-from-calgary-em-hodsman-lecture-day. Accessed August 28, 2022
Ketamine For Suicidal Ideation occurs in the podcast from 1:07:10 to
Here are the show notes from this section of the podcast:
Ketamine to relieve suicidal ideation and reduce acute risk
Biological plausibility of ketamine for suicidal ideation
Ketamine is an NMDA receptor antagonist. Little is understood about its biological plausibility for its effects on depression and suicidality. The most compelling theories revolve around the concept of neuroplasticity that appear to occur hours to days after dosing, rather than its immediate neurotransmitter effects. Animal studies suggest that pre-frontal cortex dendritic atrophy that occurs with chronic stress is partially reversed by ketamine, whose effects last for about one week.
Ketamine for depression
The interest in ketamine for depression started when a number of war veterans receiving ketamine for surgery seemed to recover from surgery with less pain and less depression. A recent systematic review of >2900 patients in 36 trials that looked at ketamine and esketamine for depression concluded that ketamine was safe and effective for treating depression. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations endorsed ketamine for treatment resistant depression as a level 1 recommendation. The antidepressant effects of ketamine are thought to start around 2 hours and last about 7 days. In patients who have resolution of suicidality after ketamine, 89% of them remain free of suicidal ideation at 7 days.
Psychiatry literature on ketamine for suicidal ideation
The most compelling evidence for treating suicidality with ketamine is from the psychiatry literature. A 2021 systematic review identified 15 studies including 9 RCT looking at esketamine and ketamine for suicidal ideation in both inpatient and outpatient psychiatry settings. The most common dose of ketamine was 0.5mg/kg IV infusion over 40min. They concluded that IV ketamine showed a rapid decrease in suicidal ideation but that the effects were short lived.
Emergency Medicine literature on ketamine for suicidal ideation
There is a paucity of EM literature for ketamine and suicidal ideation. There are only 3 prospective trials with large confidence intervals and suboptimal trial design enrolling and treating a total of 77 patients. The largest study by Kashani excluded patients with substance use disorder, and all of these trials used only 0.2mg/kg IV, a significantly lower dose than the one that has been established in the psychiatric literature of 0.5mg/kg IV over 40 minus. Keeping these caveats in mind, these studies did show significant improvements in suicidal ideation as measured by standardized psychometrics. Data from the smaller trial showed significant improvements compared to the control group at 90 min but that difference became non-significant at 230min. It appears that patients receiving ketamine improved faster, but over time they eventually caught up as their suicidal ideation resolved on its own.
Is there potential for ketamine to relieve suffering from suicidal ideation, decrease admission rates and bridge patients to ongoing care?
Currently, the EM literature points to a trend in acutely reducing suicidal ideation in patients without substance use disorder based on tiny poorly designed studies. Based on some of the psychiatry literature suggesting ketamine’s anti-suicidal ideation effects up to 7 days, it is plausible that carefully selected patients with suicidal ideation who receive ketamine in the ED may not require admission if they are ensured followup within 7 days. Larger, well designed ED RCTs are required before we consider incorporating ketamine for suicidal ideation into our practices.
- P A Zunszain. Ketamine: synaptogenesis, immunomodulation and glycogen synthase kinase-3 as underlying mechanisms of its antidepressant properties. Molecular Psychiatry volume 18, pages1236–1241 (2013).
- Anees Bahji, Carlos A. Zarate & Gustavo H. Vazquez (2022) Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis, Expert Opinion on Drug Safety.
- Swainson J, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder:. Can J Psychiatry. 2021 Feb;66(2):113-125.
- Kashani P, Yousefian S, Amini A, Heidari K, Younesian S, Hatamabadi HR. The effect of intravenous ketamine in suicidal ideation of emergency department patients. Emerg (Tehran). 2014;2(1):36–9.
- Burger J, Capobianco M, Lovern R, et al. A double-blinded, randomized, placebo- controlled sub-dissociative dose ketamine pilot study in the treatment of acute de- pression and Suicidality in a military emergency department setting. Mil Med. 2016; 181(10):1195–9.
- Domany Y, Shelton RC, McCullumsmith CB. Ketamine for acute suicidal ideation. An emergency department intervention: a randomized, double-blind, placebo- controlled, proof-of-concept trial. Depress Anxiety. 2020;37(3):224–33.