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Drugs Jan 2015Fixed-dose dextromethorphan/quinidine capsules (Nuedexta(®)) utilize quinidine to inhibit the metabolism of dextromethorphan, enabling high plasma dextromethorphan... (Review)
Review
Fixed-dose dextromethorphan/quinidine capsules (Nuedexta(®)) utilize quinidine to inhibit the metabolism of dextromethorphan, enabling high plasma dextromethorphan concentrations to be reached without using a larger dose of the drug. The drug combination is the first treatment to be approved for pseudobulbar affect (PBA), a condition of contextually inappropriate/exaggerated emotional expression that often occurs in adults with neurological damage conditions, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, traumatic brain injury, Alzheimer's disease or Parkinson's disease. Dextromethorphan/quinidine at the recommended dosages of 20/10 or 30/10 mg twice daily reduced the rate of PBA episodes and improved PBA severity in a 12-week, double-blind, placebo-controlled trial in adults with ALS or MS (STAR), with further improvements in the severity of the condition observed in a 12-week open-label extension phase. Dextromethorphan/quinidine 20/10 mg twice daily also improved PBA secondary to dementia in a cohort of a 12-week noncomparative trial (PRISM II). The drug combination was generally well tolerated in these studies, with no particular safety or tolerability concerns. Although longer-term efficacy and tolerability data for dextromethorphan/quinidine 20/10 or 30/10 mg twice daily would be beneficial, current evidence indicates that it is a useful option in the treatment of adults with PBA.
Topics: Adult; Dextromethorphan; Drug Combinations; Humans; Mood Disorders; Nervous System Diseases; Quinidine
PubMed: 25420446
DOI: 10.1007/s40265-014-0328-z -
The Consultant Pharmacist : the Journal... Apr 2014To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA). (Review)
Review
OBJECTIVE
To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA).
DATA SOURCES
A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine.
STUDY SELECTION AND DATA EXTRACTION
English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations.
DATA SYNTHESIS
PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration.
CONCLUSIONS
Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.
Topics: Clinical Trials as Topic; Crying; Dextromethorphan; Drug Combinations; Excitatory Amino Acid Antagonists; Humans; Laughter; Pseudobulbar Palsy; Quinidine; Receptors, sigma; Treatment Outcome; Sigma-1 Receptor
PubMed: 24704895
DOI: 10.4140/TCP.n.2014.264 -
American Journal of Health-system... Dec 2022
Topics: Humans; Dextromethorphan; Bupropion; Chromatography, High Pressure Liquid
PubMed: 36259787
DOI: 10.1093/ajhp/zxac292 -
Journal of Psychosocial Nursing and... Nov 2022Dextromethorphan (DXM) has been re-purposed several times over the past 7 decades: first as a cough suppressant, then as a compounded formulation with quinidine for...
Dextromethorphan (DXM) has been re-purposed several times over the past 7 decades: first as a cough suppressant, then as a compounded formulation with quinidine for treatment of pseudobulbar affect, and most recently as a compounded formulation with bupro-pion for treatment of major depressive disorder. The current article describes the history and purported mechanisms of action of DXM for each use and the uniquely rapid action and safety profile of the oral dextromethorphan- bupropion antidepressant formulation. [(11), 9-11.].
Topics: Humans; Antitussive Agents; Dextromethorphan; Depressive Disorder, Major; Quinidine; Antidepressive Agents
PubMed: 36317836
DOI: 10.3928/02793695-20221005-02 -
Archives of Pediatrics & Adolescent... Dec 2007To compare the effects of a single nocturnal dose of buckwheat honey or honey-flavored dextromethorphan (DM) with no treatment on nocturnal cough and sleep difficulty... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
OBJECTIVES
To compare the effects of a single nocturnal dose of buckwheat honey or honey-flavored dextromethorphan (DM) with no treatment on nocturnal cough and sleep difficulty associated with childhood upper respiratory tract infections.
DESIGN
A survey was administered to parents on 2 consecutive days, first on the day of presentation when no medication had been given the prior evening and then the next day when honey, honey-flavored DM, or no treatment had been given prior to bedtime according to a partially double-blinded randomization scheme.
SETTING
A single, outpatient, general pediatric practice.
PARTICIPANTS
One hundred five children aged 2 to 18 years with upper respiratory tract infections, nocturnal symptoms, and illness duration of 7 days or less.
INTERVENTION
A single dose of buckwheat honey, honey-flavored DM, or no treatment administered 30 minutes prior to bedtime.
MAIN OUTCOME MEASURES
Cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality.
RESULTS
Significant differences in symptom improvement were detected between treatment groups, with honey consistently scoring the best and no treatment scoring the worst. In paired comparisons, honey was significantly superior to no treatment for cough frequency and the combined score, but DM was not better than no treatment for any outcome. Comparison of honey with DM revealed no significant differences.
CONCLUSIONS
In a comparison of honey, DM, and no treatment, parents rated honey most favorably for symptomatic relief of their child's nocturnal cough and sleep difficulty due to upper respiratory tract infection. Honey may be a preferable treatment for the cough and sleep difficulty associated with childhood upper respiratory tract infection.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00127686.
Topics: Adolescent; Antitussive Agents; Child; Child Welfare; Child, Preschool; Cough; Dextromethorphan; Female; Health Surveys; Honey; Humans; Male; Parents; Respiratory Tract Infections; Sleep; Sleep Wake Disorders
PubMed: 18056558
DOI: 10.1001/archpedi.161.12.1140 -
Drug Metabolism Reviews May 2020Dextromethorphan (DXM) is a safe and effective antitussive agent present in several over the counter cough and cold medications. At higher doses, it causes psychoactive... (Review)
Review
Dextromethorphan (DXM) is a safe and effective antitussive agent present in several over the counter cough and cold medications. At higher doses, it causes psychoactive effects, making it appealing for abuse. In this work, the pharmacokinetics and pharmacodynamics of DXM with clinical and forensic relevance were extensively reviewed. DXM and related known metabolizing enzymes and metabolites were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Major metabolic pathways include sequential -demethylation and -demethylation of DXM, yielding dextrorphan (DXO), the major active metabolite, and 3-hydroxymorphinan, the bi-demethylated product, respectively. The demethylation order described may reverse being the resultant mid product 3-methoxymorphinan. UDP-glucuronosyltranferase produces glucuronide conjugates. Genotypic variations in enzymes and interactions with other drugs can result in large inter-individual variability in the pharmacological and toxicological effects produced. Knowing the metabolism of DXM may help to better understand the inter-individual variability in the pharmacokinetics and pharmacodynamics and to avoid adverse effects.
Topics: Animals; Antitussive Agents; Dextromethorphan; Drug Misuse; Humans
PubMed: 32393072
DOI: 10.1080/03602532.2020.1758712 -
Neurology Mar 1994
Topics: Animals; Anticonvulsants; Convulsants; Dextromethorphan; Humans
PubMed: 8179707
DOI: 10.1212/wnl.44.3_part_1.582-b -
Pharmacology & Therapeutics Mar 2016Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and... (Review)
Review
Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders.
Topics: Animals; Antitussive Agents; Dextromethorphan; Humans
PubMed: 26826604
DOI: 10.1016/j.pharmthera.2016.01.016 -
Drug Safety 1992Dextromethorphan is a highly effective and widely used nonopioid antitussive drug. As it has been in use for more than 30 years, a large body of clinical experience has... (Review)
Review
Dextromethorphan is a highly effective and widely used nonopioid antitussive drug. As it has been in use for more than 30 years, a large body of clinical experience has been used to formulate a safety profile. An anthology of adverse drug events has been analysed, drawn both from published case records and a data base recording dextromethorphan-related adverse events spontaneously reported by physicians or pharmacists. The resulting safety profile indicates that adverse drug reactions are infrequent and usually not severe. The predominant symptoms are usually dose related and include neurological, cardiovascular and gastrointestinal disturbances. Particular safety concerns arise when monoamine oxidase inhibiting (MAOI) drugs and dextromethorphan are coadministered. In addition to adverse drug reactions, the safety profile of dextromethorphan is affected by episodic and sporadic abuse. In fact, abuse appeared to be the most significant hazard identified by analysis of spontaneous adverse event reporting. No evidence could be found that the well documented pharmacokinetic polymorphism observed with dextromethorphan is correlated with any clinically significant safety risk if it is used for short term treatment. In summary, the safety profile of dextromethorphan is reassuring, particularly relating to overdose in adults and children.
Topics: Animals; Dextromethorphan; Drug Interactions; Drug Overdose; Humans; Monoamine Oxidase Inhibitors; Nervous System; Risk Factors; Substance-Related Disorders
PubMed: 1503667
DOI: 10.2165/00002018-199207030-00004 -
The American Journal of Emergency... May 1991Dextromethorphan, a common ingredient in cough syrups, has rarely been described to cause toxicity. The authors describe an unusual case of a known asthmatic presenting... (Review)
Review
Dextromethorphan, a common ingredient in cough syrups, has rarely been described to cause toxicity. The authors describe an unusual case of a known asthmatic presenting with somnolence, who appeared to be in end-stage respiratory failure. Her partial response to routine naloxone, 1 mg, was surprising. However, additional naloxone was required to completely normalize the patient's mental status. The authors suggest naloxone be administered in doses of 0.4 mg or more intravenously in suspected dextromethorphan overdose.
Topics: Adolescent; Adult; Antidotes; Antitussive Agents; Child, Preschool; Dextromethorphan; Drug Overdose; Female; Humans; Infant; Male; Naloxone; Poisoning
PubMed: 2018593
DOI: 10.1016/0735-6757(91)90085-x