The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F20%3A43920292" target="_blank" >RIV/00023752:_____/20:43920292 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/20:43920425

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00844/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00844/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fpsyt.2020.00844" target="_blank" >10.3389/fpsyt.2020.00844</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication

Popis výsledku v původním jazyce

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 &gt;8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p&lt;0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (&gt;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.

Název v anglickém jazyce

The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication

Popis výsledku anglicky

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 &gt;8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p&lt;0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (&gt;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30215 - Psychiatry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Psychiatry

ISSN

1664-0640

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

7

Strana od-do

"Article number 844"

Kód UT WoS článku

000570558700001

EID výsledku v databázi Scopus

2-s2.0-85090755590