Journal of affective disorders
April 15, 2026
Gia Han Le, Sabrina Wong, Danica E Johnson et al.
4 citations
Ketamine and esketamine rapidly reduce depression in people with treatment-resistant depression and bipolar depression, but the synaptic mechanisms behind dosing and durability are unclear. This review of 61 clinical and 17 preclinical studies found that a single 0.5 mg/kg intravenous infusion produces antidepressant effects peaking at 24 hours and fading over 2-3 days. Early neurophysiological changes appear within 3-8 hours, consolidate by 24 hours, and are rarely detected beyond 3 days. Twice-weekly and thrice-weekly dosing produce comparable four-week outcomes, and weekly maintenance reduces relapse risk. Ketamine may open a plasticity window lasting about 2-3 days, and aligning dosing intervals with this window could optimize durability while minimizing drug exposure.
Journal of psychopharmacology (Oxford, England)
June 24, 2026
Shreya Vasudeva, Gabrielle F M Lovell, Sabrina Wong et al.
Ketamine and its enantiomer esketamine show low risk of abuse, dependence, or misuse when administered under controlled clinical supervision, based on a systematic review of 30 studies (25 clinical and 5 preclinical). Clinical studies found minimal evidence of craving, dose escalation, or illicit use in monitored settings. Preclinical work indicated that (S)-ketamine produces reward-related behaviors, racemic ketamine shows reinforcing effects at higher doses, and (R)-ketamine has minimal reinforcing effects. Abuse risk was identified mainly in case reports lacking proper monitoring. The findings support safe incorporation of ketamine into mood disorder treatment protocols with structured administration and ongoing monitoring.
General hospital psychiatry
January 1, 2026
Gabrielle F M Lovell, Shreya Vasudeva, Diana K Orsini et al.
Ketamine, an anesthetic also used for mood and anxiety disorders, may cause mild, temporary elevations in liver enzymes, but serious liver damage appears rare. A systematic review of 13 studies (5 randomized trials, 3 observational studies, and 5 case reports) involving 1,017 patients—mostly with major depressive disorder or bipolar disorder—found 75 mild liver enzyme elevations across trials, with only a few cases of impaired liver function. No cases met Hy's Law criteria for severe drug-induced liver injury. Case reports described more severe liver issues that improved with dose reduction or stopping treatment. Routine liver monitoring during ketamine treatment remains advisable.