In an open-label extension of a prior crossover trial, oral ketamine was given for six weeks to people with treatment-resistant depression, post-traumatic stress disorder, or obsessive-compulsive disorder. Doses started at 1-1.5 mg/kg and increased to 1.5-2.5 mg/kg, taken one to three times per week. Symptom scores remained low throughout the six weeks, and the oral formulation was well tolerated with few side effects. The findings suggest that oral ketamine can sustain improvements in these treatment-resistant conditions and offers a practical alternative for maintenance therapy.
Ketamine reduces obsessive-compulsive symptoms more than a psychoactive control (fentanyl) in people with severe, treatment-resistant OCD. In a small double-blind trial, participants received a single intramuscular dose of either 0.5 mg/kg ketamine, 1.0 mg/kg ketamine, or 50 µg fentanyl. Both ketamine doses produced greater and dose-related reductions on the Yale-Brown Obsessive-Compulsive Scale, with effects separating from fentanyl within 1–2 hours and persisting for up to 168 hours. Ketamine caused short-term dissociative and cardiovascular effects; two of twelve participants dropped out due to not tolerating dissociation. The findings provide preliminary evidence for ketamine's efficacy and tolerability in an outpatient cohort.
Intramuscular ketamine shows preliminary effectiveness and is well tolerated by people with posttraumatic stress disorder in a community setting. The findings are encouraging given the known limitations of existing treatments, but more research is needed to determine the best dosing schedule and long-term role of ketamine for PTSD.
A randomized controlled trial will test the feasibility of adding behavioral activation therapy (BAT) to oral ketamine for treatment-resistant major depressive disorder. The study aims to recruit 60 adults aged 18–65 years, randomizing them to eight weeks of oral ketamine with BAT or oral ketamine alone. Feasibility will be measured by attendance, acceptability, and retention. The primary efficacy outcome is the Montgomery-Asberg Depression Rating Scale, assessed weekly during treatment and fortnightly during 12 weeks of follow-up. For a definitive trial to be recommended, the study must meet recruitment targets and show a greater than 20% reduction in relapse rates favoring the combined treatment arm.