Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials

Bettina Diekamp,1 Stephane Borentain,2 Dong-Jing Fu,3 Robert Murray,4 Kristin Heerlein,1 Qiaoyi Zhang,5 Cornelius Schüle,6 Maju Mathews2 1Department of Medical and Scientific Affairs, Janssen-Cilag GmbH, Neuss, Germany; 2Department of Global Medical Affairs, Janssen Research & Development LLC, T...

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Autores principales:	Diekamp B, Borentain S, Fu DJ, Murray R, Heerlein K, Zhang Q, Schüle C, Mathews M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	esketamine benzodiazepine depression suicidal ideation rapid-acting Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a411f610d609435393ad87721156590b
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spelling	oai:doaj.org-article:a411f610d609435393ad87721156590b2021-12-02T18:31:00ZEffect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials1178-2021https://doaj.org/article/a411f610d609435393ad87721156590b2021-07-01T00:00:00Zhttps://www.dovepress.com/effect-of-concomitant-benzodiazepine-use-on-efficacy-and-safety-of-esk-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Bettina Diekamp,1 Stephane Borentain,2 Dong-Jing Fu,3 Robert Murray,4 Kristin Heerlein,1 Qiaoyi Zhang,5 Cornelius Schüle,6 Maju Mathews2 1Department of Medical and Scientific Affairs, Janssen-Cilag GmbH, Neuss, Germany; 2Department of Global Medical Affairs, Janssen Research & Development LLC, Titusville, NJ, USA; 3Department of Neuroscience Clinical Development, Janssen Research & Development LLC, Titusville, NJ, USA; 4Neuroscience Clinical Biostatistics, Janssen Research & Development LLC, Titusville, NJ, USA; 5Global Market Access, Neuroscience, Janssen Global Services, LLC, Titusville, NJ, USA; 6Ludwig-Maximilians-University Munich, Clinic for Psychiatry and Psychotherapy, Munich, GermanyCorrespondence: Bettina DiekampDepartment of Medical and Scientific Affairs, Janssen-Cilag GmbH, Johnson & Johnson Platz 1, Neuss, 41470, GermanyTel +49-21379556179Email bdiekamp@its.jnj.comPurpose: The impact of benzodiazepines on the efficacy and safety of esketamine as a rapid-acting antidepressant remains unclear.Materials and Methods: Data from two identically designed, randomized double-blind studies were pooled and analyzed on a post-hoc basis. In both studies, adults with major depressive disorder with acute suicidal ideation or behavior were randomized to placebo or esketamine 84 mg nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care (initial hospitalization and newly initiated or optimized oral antidepressant[s]). Efficacy and safety were analyzed in two groups based on whether patients used concomitant benzodiazepines, which were prohibited within 8 hours before and 4 hours after the first dose of esketamine and within 8 hours of the primary efficacy assessment at 24 hours. The primary efficacy endpoint – change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score – was analyzed using ANCOVA.Results: Most patients (309/451, 68.5%) used concomitant benzodiazepines. Greater decrease in MADRS total score was observed with esketamine (mean [SD]: − 16.1 [11.73]) versus placebo (− 12.6 [10.56]) at 24 hours (least-squares mean difference: − 3.7, 95% CI: − 5.76, − 1.59). The differences between the esketamine and placebo groups were clinically meaningful, irrespective of benzodiazepine use (benzodiazepine: − 4.3 [− 6.63, − 1.89]; no benzodiazepine: − 3.1 [− 6.62, 0.45]). Among patients taking esketamine, change in MADRS total score was not significantly different between patients taking benzodiazepines (− 15.8 [11.27]) versus those not taking benzodiazepines (− 16.8 [12.82]) (least-squares mean difference: 1.1, [− 2.24, 4.45]). Among esketamine-treated patients, the incidence of sedation was higher with benzodiazepine use, whereas dissociation was similar.Conclusion: Benzodiazepines do not meaningfully affect the rapid-acting antidepressant effect of esketamine at 24 hours post-first dose among patients with MDD and acute suicidal ideation or behavior.Keywords: esketamine, benzodiazepine, depression, suicidal ideation, rapid-actingDiekamp BBorentain SFu DJMurray RHeerlein KZhang QSchüle CMathews MDove Medical Pressarticleesketaminebenzodiazepinedepressionsuicidal ideationrapid-actingNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2347-2357 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	esketamine benzodiazepine depression suicidal ideation rapid-acting Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	esketamine benzodiazepine depression suicidal ideation rapid-acting Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Diekamp B Borentain S Fu DJ Murray R Heerlein K Zhang Q Schüle C Mathews M Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
description	Bettina Diekamp,1 Stephane Borentain,2 Dong-Jing Fu,3 Robert Murray,4 Kristin Heerlein,1 Qiaoyi Zhang,5 Cornelius Schüle,6 Maju Mathews2 1Department of Medical and Scientific Affairs, Janssen-Cilag GmbH, Neuss, Germany; 2Department of Global Medical Affairs, Janssen Research & Development LLC, Titusville, NJ, USA; 3Department of Neuroscience Clinical Development, Janssen Research & Development LLC, Titusville, NJ, USA; 4Neuroscience Clinical Biostatistics, Janssen Research & Development LLC, Titusville, NJ, USA; 5Global Market Access, Neuroscience, Janssen Global Services, LLC, Titusville, NJ, USA; 6Ludwig-Maximilians-University Munich, Clinic for Psychiatry and Psychotherapy, Munich, GermanyCorrespondence: Bettina DiekampDepartment of Medical and Scientific Affairs, Janssen-Cilag GmbH, Johnson & Johnson Platz 1, Neuss, 41470, GermanyTel +49-21379556179Email bdiekamp@its.jnj.comPurpose: The impact of benzodiazepines on the efficacy and safety of esketamine as a rapid-acting antidepressant remains unclear.Materials and Methods: Data from two identically designed, randomized double-blind studies were pooled and analyzed on a post-hoc basis. In both studies, adults with major depressive disorder with acute suicidal ideation or behavior were randomized to placebo or esketamine 84 mg nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care (initial hospitalization and newly initiated or optimized oral antidepressant[s]). Efficacy and safety were analyzed in two groups based on whether patients used concomitant benzodiazepines, which were prohibited within 8 hours before and 4 hours after the first dose of esketamine and within 8 hours of the primary efficacy assessment at 24 hours. The primary efficacy endpoint – change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score – was analyzed using ANCOVA.Results: Most patients (309/451, 68.5%) used concomitant benzodiazepines. Greater decrease in MADRS total score was observed with esketamine (mean [SD]: − 16.1 [11.73]) versus placebo (− 12.6 [10.56]) at 24 hours (least-squares mean difference: − 3.7, 95% CI: − 5.76, − 1.59). The differences between the esketamine and placebo groups were clinically meaningful, irrespective of benzodiazepine use (benzodiazepine: − 4.3 [− 6.63, − 1.89]; no benzodiazepine: − 3.1 [− 6.62, 0.45]). Among patients taking esketamine, change in MADRS total score was not significantly different between patients taking benzodiazepines (− 15.8 [11.27]) versus those not taking benzodiazepines (− 16.8 [12.82]) (least-squares mean difference: 1.1, [− 2.24, 4.45]). Among esketamine-treated patients, the incidence of sedation was higher with benzodiazepine use, whereas dissociation was similar.Conclusion: Benzodiazepines do not meaningfully affect the rapid-acting antidepressant effect of esketamine at 24 hours post-first dose among patients with MDD and acute suicidal ideation or behavior.Keywords: esketamine, benzodiazepine, depression, suicidal ideation, rapid-acting
format	article
author	Diekamp B Borentain S Fu DJ Murray R Heerlein K Zhang Q Schüle C Mathews M
author_facet	Diekamp B Borentain S Fu DJ Murray R Heerlein K Zhang Q Schüle C Mathews M
author_sort	Diekamp B
title	Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
title_short	Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
title_full	Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
title_fullStr	Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
title_full_unstemmed	Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials
title_sort	effect of concomitant benzodiazepine use on efficacy and safety of esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior: pooled randomized, controlled trials
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a411f610d609435393ad87721156590b
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Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials

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