Samuel T Wilkinson1,2, Taeho Greg Rhee1, Jutta Joormann3, Ryan Webler4, Mayra Ortiz Lopez5, Brandon Kitay1,6, Madonna Fasula1, Christina Elder1, Lisa Fenton1, Gerard Sanacora1,2. 1. Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA. 2. Interventional Psychiatric Service, Yale School of Medicine, New Haven, Connecticut, USA. 3. Department of Psychology, Yale University, New Haven, Connecticut, USA. 4. Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA. 5. Department of Nursing, Southern Connecticut State University, New Haven, Connecticut, USA. 6. Department of Psychiatry and Behavioral Sciences, Emory School of Medicine, Atlanta, Georgia, USA.
Abstract
INTRODUCTION:Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. OBJECTIVE: We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD). METHODS: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. RESULTS: Of the 42 patients who signed consent, 28 patients achieved a response and were randomized toCBT 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 d = 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 (F = 4.58; p = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen d = 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 (N = 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 (t[8] = 2.33; p < 0.05) whereas nonresponders did not (t[10] <1; p ns). CONCLUSIONS: 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.
RCT Entities:
INTRODUCTION:Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. OBJECTIVE: We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD). METHODS: 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. RESULTS: 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 d = 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 (F = 4.58; p = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen d = 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 (N = 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 (t[8] = 2.33; p < 0.05) whereas nonresponders did not (t[10] <1; p ns). CONCLUSIONS: 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.
Authors: Sandra J Drozdz; Akash Goel; Matthew W McGarr; Joel Katz; Paul Ritvo; Gabriella F Mattina; Venkat Bhat; Calvin Diep; Karim S Ladha Journal: J Pain Res Date: 2022-06-15 Impact factor: 2.832