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.
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.