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

Summary & key facts

Researchers tested whether adding cognitive behavioral therapy (CBT) could keep the fast antidepressant effect of ketamine going in people whose depression had not improved with other treatments. Sixteen people started a short course of four ketamine infusions over two weeks while also doing 12 CBT sessions across ten weeks. About half felt better after ketamine, and some kept feeling better for weeks after the last infusion. The study was small and not blinded, so the results are only suggestive. Bigger controlled trials are needed to know if CBT really helps people avoid long-term ketamine use.

Key facts:

• Sixteen people with treatment-resistant depression took part in the study.
• Each person received four ketamine infusions over two weeks and began a 12-session CBT course that lasted ten weeks.
• About half of the participants (8 people) responded to the ketamine treatment during the first two weeks.
• About four in ten people (7 people) reached remission, meaning their symptoms dropped to a low level, in the first two weeks.
• Among the eight people who responded to ketamine, two had relapsed by the end of the CBT course (about eight weeks after the last ketamine), which is roughly one quarter.
• Over a longer follow-up, five of the eight initial responders eventually relapsed. The middle point for relapse was about 12 weeks after the ketamine infusions.
• Among the seven people who reached remission, three stayed in remission for at least four weeks after ketamine, and two stayed in remission for at least eight weeks.
• People who did not respond to ketamine did not seem to get benefit from adding CBT in this study.
• The study was open-label (participants and researchers knew what treatment was given) and small, so the authors say larger, well-controlled trials are needed to test whether CBT truly helps sustain ketamine’s antidepressant effects.

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.

Topics

Neurotransmitter Receptor Influence on Behavior Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Anesthesia Antidepressant Clinical trial Cognition Depression (economics) Economics Hippocampus Internal medicine Ketamine Macroeconomics Major depressive disorder Medicine Psychiatry Psychology Randomized controlled trial Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood