In a pilot study of ten adults with treatment-resistant depression, combining low-dose ketamine with a psychotherapeutic protocol called Therapeutic Reset of Internal Processes (TRIP) led to a significant reduction in depressive symptoms. Patients' average depression score on the PHQ-9 fell from 17.9 (moderate range) before treatment to 9.5 after treatment, a decrease of about 47%. The authors suggest that adding this specific therapy may enhance the effects of ketamine, but note that controlled trials with comparison groups are needed.
Ketamine shows promise for treating major depression in patients who have not responded to standard antidepressants, including those with a history of chronic pain. The findings suggest that ketamine's rapid antidepressant effects may be particularly beneficial for this difficult-to-treat population, though the exact mechanisms remain under investigation.