Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

Ketamine provides rapid but short-lived antidepressant effects. In an open-label trial, patients with treatment-resistant depression received a 2-week course of intravenous ketamine alongside a 10-week course of cognitive behavioral therapy (CBT). Of 16 participants, 8 responded to ketamine and 7 achieved remission in the first 2 weeks. Among responders, 25% relapsed by the end of CBT, and the median time to relapse was 12 weeks after ketamine. Among remitters, 2 of 7 maintained remission through 8 weeks after ketamine. Ketamine nonresponders did not benefit from CBT. The combination may help sustain ketamine's effects, but randomized controlled trials are needed.

Study at a glance

Abstract

Introduction: Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. Methods: Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol. Results: Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT. Conclusions: CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects.