Australian & New Zealand Journal of Psychiatry
November 15, 2019
Katrina Witt, Jennifer Potts, Anna A.m. Hubers et al.
203 citations
A single infusion of ketamine may reduce suicidal thoughts in people with treatment-resistant depression within four hours, and the effect can last up to 72 hours. The analysis combined 15 randomized controlled trials with 572 participants, mostly with mood disorders. At four hours after infusion, suicidal ideation scores dropped significantly (standardized mean difference -0.51), and the reduction persisted through 72 hours (standardized mean difference -0.57 to -0.63 at different intervals) but not beyond. Results varied widely across studies, and evidence quality was moderate to low. There were almost no data on whether ketamine prevents actual suicide attempts or self-harm. Further trials are needed to confirm these findings and find ways to sustain the anti-suicidal effect.
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
JAMA Network Open
August 12, 2020
Matthew S. Milak, Rain Rashid, Zhengchao Dong et al.
59 citations
A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder within hours. In this randomized clinical trial of 38 adults, higher ketamine doses and blood levels correlated with greater improvement on the Hamilton Depression Rating Scale 24 hours later. However, the brain's glutamate+glutamine (Glx) response to ketamine mediated this relationship: lower Glx responses predicted better antidepressant effects. GABA levels did not correlate with antidepressant benefit. Adverse effects were linked to blood levels only in men. The findings suggest that ketamine's antidepressant mechanism involves reducing Glx levels in the ventromedial prefrontal cortex.
The International Journal of Neuropsychopharmacology
April 1, 2024
Sumra Sajid, Hanga C Galfalvy, John G Keilp et al.
9 citations
In a randomized, midazolam-controlled trial of 40 suicidal, depressed participants given intravenous ketamine, acute dissociative and psychotomimetic effects were not associated with changes in suicidal ideation or depressive symptoms from before to after infusion. Norketamine showed a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection, suggesting dissociation may be more an effect of the parent drug. Dehydronorketamine correlated with dissociative symptoms at multiple time points. No evidence was found that ketamine's acute, transient dissociative or psychotomimetic effects contribute to its antidepressant or anti-suicidal actions.
Translational Psychiatry
February 6, 2025
Sumra Sajid, J John Mann, Michael F Grunebaum
3 citations
Ketamine and its enantiomers can reduce suicidal thoughts, but the effects are short-lived and vary by dose and route of administration. A systematic review of 16 clinical trials since 2020 found that multiple intravenous doses of ketamine or S-ketamine reduced suicidal ideation for several days to weeks, while single doses had shorter, less consistent effects. Intranasal and single intravenous doses produced less reliable results. R-ketamine showed fewer side effects but requires more research. No studies measured suicidal behavior as an outcome. The review highlights the need for personalized treatment and notes limitations such as small samples and study heterogeneity.
Journal of Affective Disorders
November 1, 2026
Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp et al.
A midazolam-controlled trial of intravenous ketamine for suicidal depressed patients found that ketamine rapidly reduced suicidal ideation within 24 hours. An exploratory analysis measured saliva cortisol awakening response at baseline and 24 hours after infusion. Waking cortisol significantly increased 24 hours after ketamine treatment. The increase in waking cortisol from baseline to post-infusion showed a small to medium, nonsignificant correlation with decreased suicidal ideation. These preliminary results, pending replication, align with evidence that moderate cortisol increases may enhance stress-resilience.