OPEN Foundation

R. Ostroff

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.
Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2017). Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression. Psychotherapy and Psychosomatics86(3), 162-167. 10.1159/000457960
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Reply to: Ketamine and Psychosis History: Antidepressant Efficacy and Psychotomimetic Effects Postinfusion

Abstract

New and encouraging findings regarding the use of ketamine for depression in the context of psychotic symptoms have been published by Pennybaker et al. (1). In their analysis, patients with bipolar disorder without a history of psychosis had a more robust response to ketamine, and patients with a history of psychosis had a significant response compared with placebo as well. Concerning dissociative symptoms, even though patients with a history of psychosis endorsed more symptoms, these were not maintained after a 40-minute period, and no full psychosis was induced in their sample.

da Frota Ribeiro, C. M., Sanacora, G., & Ostroff, R. (2017). Reply to: Ketamine and Psychosis History: Antidepressant Efficacy and Psychotomimetic Effects Postinfusion. Biological Psychiatry. 10.1016/j.biopsych.2017.01.012
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The use of ketamine for the treatment of depression in the context of psychotic symptoms

Abstract

Mounting evidence from a series of small clinical trials and case series suggests ketamine can have rapid and robust antidepressant(1), and possibly anti-suicidal effects(2) in patients who had not responded to standard treatment options. However, due to ketamine’s variable psychotomimetic effects in healthy volunteers and exacerbation of previously experienced positive symptoms in schizophrenic volunteers(3,4), patients previously experiencing psychotic features have been excluded from the reported studies and trials.

da Frota Ribeiro, C. M., Sanacora, G., Hoffman, R., & Ostroff, R. (2015). The use of ketamine for the treatment of depression in the context of psychotic symptoms. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2015.05.016
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