Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial
Psychotherapy and Psychosomatics – January 01, 2021
Source: CrossRef
Summary
Ketamine's rapid antidepressant effects in treatment-resistant depression can be sustained longer with cognitive behavioral therapy. Of 42 patients, 28 responders to initial ketamine infusions were randomized. Those receiving CBT for 14 weeks showed greater sustained improvement in depressive symptoms compared to standard care, with a moderate-to-large effect size (Cohen *d* = 0.71). Furthermore, 8 ketamine responders from a 20-patient subset demonstrated improved emotional processing. This approach offers a promising strategy to maintain ketamine's benefits.
Abstract
<b><i>Introduction:</i></b> Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. <b><i>Objective:</i></b> We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD). <b><i>Methods:</i></b> Subjects with TRD were recruited and treated with 6 intravenous infusions of ketamine over 3 weeks. Subjects who experienced a clinical response (≥50% improvement in depression severity) were then randomized to receiving CBT or treatment as usual (TAU) for an additional 14 weeks, using a sequential treatment model. <b><i>Results:</i></b> Of the 42 patients who signed consent, 28 patients achieved a response and were randomized to CBT or TAU. When measured using the Montgomery-Asberg Depression Rating Scale (primary outcome measure), the effect size at the end of the study was moderate (Cohen <i>d</i> = 0.65; 95% CI –0.55 to 1.82), though the group-by-time interaction effect was not significant. There was a significant group-by-time interaction as measured by the Quick Inventory of Depressive Symptomatology (<i>F</i> = 4.58; <i>p</i> = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen <i>d</i> = 0.71 (95% CI –0.30 to 1.70) at the end of the study (14 weeks following the last ketamine infusion). In a subset of patients (<i>N</i> = 20) who underwent cognitive testing using the emotional N-back assessments before and after ketamine, ketamine responders showed improvement in the accuracy of emotional N-back (<i>t</i>[8] = 2.33; <i>p</i> < 0.05) whereas nonresponders did not (<i>t</i>[10] <1; <i>p</i> ns). <b><i>Conclusions:</i></b> This proof-of-concept study provides preliminary data indicating that CBT may sustain the antidepressant effects of ketamine in TRD. Further study and optimization of this treatment approach in well-powered clinical trials is recommended.