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

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.

Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale

“…We utilized existing quantitative data from several sources: a randomized controlled trial of ketamine versus saline placebo, which included a subsequent open-label phase (N = 67) (Singh et al, 2016), an open-label trial of ketamine (N = 16) (Wilkinson et al, 2017), and data from the Interventional Psychiatric Services at X University (N = 27) that provides ketamine as clinical treatment to patients refractory to other forms of therapy and uses the CADSS as a standard clinical safety measure. Inclusion and exclusion criteria from previous studies has been published elsewhere (Singh et al, 2016; Wilkinson et al, 2017).…”

“…Inclusion and exclusion criteria from previous studies has been published elsewhere (Singh et al, 2016; Wilkinson et al, 2017). For the clinical sample, no specific inclusion/exclusion criteria were applied other than clinically appropriate for ketamine treatment.…”

“…Anecdotal evidence derived from the experience of the authors’ use of ketamine in several clinical trials (Singh et al, 2016; Valentine et al, 2011; Wilkinson et al, 2017) as well as in a general clinical setting suggests that the CADSS does not adequately capture the acute psychoactive experience that occurs when patients with depression receive subanesthetic doses of ketamine seen in previous trials. For example, a number of patients who score zero, or close to zero on the CADSS 40 min into a ketamine infusion remark that they feel “out of it”, but that the questions of the CADSS do not accurately reflect what they are experiencing.…”

What Is New about New Antidepressants?

“…An approach to prolonging the antidepressant effect of ketamine was tested in an open-label study of 16 MDD patients (mean age 42.7 years) with a mean duration of the current episode of 47 months who had failed an average of 2.64 antidepressant trials; 6 patients (37.5%) had a history of receiving ECT in the past, but their response was not noted [55]. All patients received 2 intravenous doses of ketamine a week for 2 weeks and started cognitive behavior therapy (CBT) after the first ketamine infusion.…”

“…By consensus, response is defined as a 50% improvement in depression rating scale scores, and remission is defined as a decrease to the equivalent of 7 or less on the Hamilton Depression Rating Scale or a MADRS score of 9–10 or less [55, 74]. Considering initial scores in the range of 20–30, a patient in remission would be one third as depressed after treatment.…”