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Andrashko V, Novak T, Brunovsky M, et al. The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication. Front Psychiatry. 2020;11:844doi: 10.3389/fpsyt.2020.00844.
Andrashko, V., Novak, T., Brunovsky, M., Klirova, M., Sos, P., & Horacek, J. (2020). The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication. Frontiers in psychiatry, 11844. https://doi.org/10.3389/fpsyt.2020.00844
Andrashko, Veronika, et al. "The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication." Frontiers in psychiatry vol. 11 (2020): 844. doi: https://doi.org/10.3389/fpsyt.2020.00844
Andrashko V, Novak T, Brunovsky M, Klirova M, Sos P, Horacek J. The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication. Front Psychiatry. 2020 Aug 28;11:844. doi: 10.3389/fpsyt.2020.00844. eCollection 2020. PMID: 33005153; PMCID: PMC7485124.
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Front Psychiatry. 2020 Aug 28;11:844. doi: 10.3389/fpsyt.2020.00844. eCollection 2020.

The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication.

Frontiers in psychiatry

Veronika Andrashko, Tomas Novak, Martin Brunovsky, Monika Klirova, Peter Sos, Jiri Horacek

Affiliations

  1. Clinical Research of Mental Disorders, National Institute of Mental Health, Klecany, Czechia.
  2. Third Faculty of Medicine, Charles University, Prague, Czechia.

PMID: 33005153 PMCID: PMC7485124 DOI: 10.3389/fpsyt.2020.00844

Abstract

The rapid antidepressant effect of ketamine has become a breakthrough in the research and treatment of depression. Although predictive and modulating factors of the response to ketamine are broadly studied, little is known about optimal concurrent medication protocols. Concerning gamma-aminobutyric acid neurotransmission being a shared target for both ketamine and benzodiazepines (BZD), we evaluated the influence of BZD on the antidepressant effect of a single ketamine infusion in depressed patients. Data from 47 patients (27 females) with major depression (MADRS ≥ 20, ≥ 1 prior nonresponse to antidepressant treatment in current episode) who participated in two previous studies (EudraCT Number: 2009-010625-39 and 2013-000952-17) entered the analysis. All of the subjects were given an infusion of a subanesthetic dose of racemic ketamine (0.54 mg per kg) as an add-on medication to ongoing antidepressant treatment. Thirteen patients (28%) reached ≥ 50% reduction in MADRS within one week after ketamine administration. Nineteen (40%) patients took concomitant benzodiazepines on a daily basis. The doses of BZDs were significantly higher in nonresponders (p=0.007). ROC analysis distinguished responders from nonresponders by a criterion of >8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p<0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (>8mg of DZ equivalent) and BZD- (≤8mg of DZ equivalent) groups, with a significantly worse outcome in BZD+ on day 3 (p=0.04) and day 7 (p=0.02). The results of the study indicate that concomitant benzodiazepine treatment in higher doses may attenuate ketamine's antidepressant effect. The pathophysiological, clinical and methodological implications of this finding should be considered in future research and ketamine treatment.

Copyright © 2020 Andrashko, Novak, Brunovsky, Klirova, Sos and Horacek.

Keywords: antidepressant; benzodiazepines; clinical effect; concomitant medication; depression; ketamine

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