Psychiatry Research
August 15, 2025
Sipan Haikazian, Roger S McIntyre, Shakila Meshkat et al.
7 citations
Ketamine infusions, given intravenously at sub-anesthetic doses, reduced depression and suicidality scores in patients with treatment-resistant major depressive disorder and treatment-resistant bipolar depression. Improvements from an acute course persisted during maintenance infusions over weeks and months, with no cases of suicidal behavior or addiction. One bipolar patient (4%) experienced an affective switch that stabilized. These results provide preliminary support for the long-term use of maintenance ketamine infusions.
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
In randomized clinical trials of psychedelic drugs for psychiatric disorders, the drugs' strong subjective effects often reveal which treatment participants or raters think they received, a phenomenon called functional unblinding. A systematic review of 112 trials found that only 29.5% assessed whether blinding was maintained, yet 57.1% cited blinding as a limitation. Blinding failure exceeded 90% in psilocybin, LSD, and ayahuasca studies and 85% in MDMA trials with inert placebos. Ketamine trials rarely assessed blinding but fared better when midazolam was used as an active comparator. No control strategy consistently preserved ideal blinding, raising concerns about the validity of efficacy estimates.
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.
Expert Opinion on Pharmacotherapy
January 22, 2026
Diana Orsini, Sara Di Luch, Gabrielle F. M. Lovell et al.
A large body of evidence from clinical trials and real-world studies supports the antidepressant effects of intravenous ketamine and intranasal esketamine. Larger studies have provided reassuring safety data, including for long-term treatment. Alternative routes of administration show promise for scalability, but their efficacy relative to intravenous ketamine remains unclear. Preliminary data suggest ketamine may also be effective for bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Challenges include functional unblinding, expectancy-related bias, and treatment costs.
General Hospital Psychiatry
January 1, 2026
Gabrielle F. M. Lovell, Shreya Vasudeva, Diana 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.