A single dose of ketamine rapidly reduces suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. The effect is moderate to large and partially independent of changes in depressive symptoms. The analysis combined data from 167 participants across 10 studies comparing ketamine to a placebo (saline or midazolam). Ketamine significantly improved clinician-rated and self-reported suicidal ideation, though not on one self-report measure (the Beck Depression Inventory). The authors call for further research on long-term safety and suicide risk reduction before clinical use.
Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence in rats. The drug rapidly penetrates the brain, reaching peak concentrations within 15 minutes after administration. Ketamine also produces marked hyperlocomotion and deficits in prepulse inhibition of the acoustic startle reaction, a measure of sensorimotor gating. The maximum levels of EEG change correlate with the kinetics of ketamine, and the effects are most pronounced at 10-15 minutes after administration of 30 mg/kg.
Concomitant benzodiazepine treatment at higher doses may attenuate the rapid antidepressant effect of a single ketamine infusion. In 47 patients with major depression who received 0.54 mg/kg ketamine as an add-on to ongoing antidepressants, 28% achieved at least a 50% reduction in depression severity within one week. Patients taking more than 8 mg of diazepam equivalent daily showed a significantly worse response on days 3 and 7 compared to those taking lower doses or none. Nonresponders had significantly higher benzodiazepine doses. The findings suggest that higher benzodiazepine doses interfere with ketamine's efficacy, with implications for clinical protocols and future research.