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.
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.