Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression
Samuel T. Wilkinson, Dashaun Wright, Madonna K. Fasula, Lisa Fenton, Matthew Griepp, Robert B. Ostroff, Gerard Sanacora
Psychotherapy and Psychosomatics January 1, 2017 DOI: 10.1159/000457960
Summary
Combining cognitive behavioral therapy (CBT) with ketamine may extend its antidepressant benefits for treatment-resistant depression. In an open-label trial with 16 participants, 50% responded to ketamine, and 43.8% achieved remission. Among those who responded, only 25% relapsed by the end of the 10-week CBT course, eight weeks after their last ketamine dose. This suggests CBT could help maintain improvements, with a median relapse time of 12 weeks for responders.
Abstract
<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.