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

Psychother Psychosom. 2017;86(3):162-167. doi: 10.1159/000457960. Epub 2017 May 11.

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.

Keywords: Cognition; Cognitive behavior therapy; Ketamine; Major depressive disorder; Relapse; Treatment-resistant depression.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Adult
  • Antidepressive Agents / pharmacology*
  • Cognition
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Depressive Disorder, Major / therapy*
  • Depressive Disorder, Treatment-Resistant / therapy*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ketamine / pharmacology*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Recurrence
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Antidepressive Agents
  • Ketamine