Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

Kerri A Schoedel,1 Sarah A Morrow,2 Edward M Sellers3,4 1Altreos Research Partners, Inc., Toronto, 2Western University, London, 3DL Global Partners, Inc., Toronto, 4University of Toronto, Toronto, Ontario, Canada Abstract: Pseudobulbar affect (PBA) is a common manifestation of brain pathology ass...

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Autores principales:	Schoedel KA, Morrow SA, Sellers EM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/930cbf7bce314eed9687b3801c1446fe
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spelling	oai:doaj.org-article:930cbf7bce314eed9687b3801c1446fe2021-12-02T04:59:28ZEvaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect1178-2021https://doaj.org/article/930cbf7bce314eed9687b3801c1446fe2014-06-01T00:00:00Zhttp://www.dovepress.com/evaluating-the-safety-and-efficacy-of-dextromethorphanquinidine-in-the-a17375https://doaj.org/toc/1178-2021 Kerri A Schoedel,1 Sarah A Morrow,2 Edward M Sellers3,4 1Altreos Research Partners, Inc., Toronto, 2Western University, London, 3DL Global Partners, Inc., Toronto, 4University of Toronto, Toronto, Ontario, Canada Abstract: Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients with underlying risk factors for torsade de pointes and in those receiving medications that may interact with DM/Q. Keywords: clinical pharmacology, Nuedexta, drug interactions, CYP2D6, QTc interval, CNS-LSSchoedel KAMorrow SASellers EMDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2014, Iss default, Pp 1161-1174 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Schoedel KA Morrow SA Sellers EM Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
description	Kerri A Schoedel,1 Sarah A Morrow,2 Edward M Sellers3,4 1Altreos Research Partners, Inc., Toronto, 2Western University, London, 3DL Global Partners, Inc., Toronto, 4University of Toronto, Toronto, Ontario, Canada Abstract: Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients with underlying risk factors for torsade de pointes and in those receiving medications that may interact with DM/Q. Keywords: clinical pharmacology, Nuedexta, drug interactions, CYP2D6, QTc interval, CNS-LS
format	article
author	Schoedel KA Morrow SA Sellers EM
author_facet	Schoedel KA Morrow SA Sellers EM
author_sort	Schoedel KA
title	Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
title_short	Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
title_full	Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
title_fullStr	Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
title_full_unstemmed	Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
title_sort	evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/930cbf7bce314eed9687b3801c1446fe
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Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

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