dextromethorphan---quinidine-combination and Multiple-Sclerosis

Pseudobulbar affect (PBA) is a socially debilitating condition that primarily affects people with neurologic diseases, such as Alzheimer's disease or multiple sclerosis. This condition is characterized by uncontrolled, exaggerated expressions of laughing or crying-often when the situation does not warrant this behavior. Although the true prevalence of PBA is surprisingly high, this condition remains widely misdiagnosed and underdiagnosed. While its exact etiology is unknown, PBA likely results from disruptions in the brain structures and/or neurotransmitters that regulate emotions. Differential diagnosis of PBA includes ruling out depression or other psychiatric conditions. Treatment of PBA has traditionally centered on antidepressant therapies, but newer therapeutic options include combination agents employing multiple modalities. Therapy should include patient counseling to reassure patients and families that PBA is not the fault of the individual. Counseling should also emphasize safety precautions to minimize adverse events and maximize appropriate adherence to the selected therapies.

Topics: Affective Symptoms; Crying; Dextromethorphan; Drug Combinations; Female; Humans; Laughter; Middle Aged; Multiple Sclerosis; Neurotransmitter Agents; Quinidine

Pseudobulbar affect is characterized by uncontrollable, inappropriate laughing and/or crying that is either unrelated or out of proportion to the emotions felt by the patient and occurs in patients with neurological disorders, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis or traumatic brain injury. Dextromethorphan/quinidine is indicated in the US for the treatment of pseudobulbar affect. Dextromethorphan, when its metabolism is inhibited by the coadministration of quinidine, has been shown to have a positive effect on the symptoms of pseudobulbar affect. Dextromethorphan/quinidine 20 mg/10 mg twice daily was associated with a significantly greater decrease in the rate of pseudobulbar affect episodes per day (primary endpoint) than placebo in the 12-week, randomized, double-blind, placebo-controlled, multicentre STAR trial (Safety, Tolerability, And efficacy Results trial of AVP-923 in PBA [pseudobulbar affect]) involving patients with pseudobulbar affect and ALS or multiple sclerosis. Moreover, the mean change from baseline in Center for Neurologic Study-Lability Scale score at 12 weeks was significantly greater among recipients of dextromethorphan/quinidine 20 mg/10 mg twice daily than those receiving placebo. Dextromethorphan/quinidine 20 mg/10 mg twice daily was generally well tolerated. The drug has been shown to cause dosage-dependent corrected QT interval (QTc) prolongation; however, in the STAR trial, dextromethorphan/quinidine 20 mg/10 mg twice daily appeared to be well tolerated with regard to QTc prolongation.

Topics: Amyotrophic Lateral Sclerosis; Crying; Dextromethorphan; Drug Combinations; Emotions; Female; Humans; Laughter; Male; Mood Disorders; Multiple Sclerosis; Quinidine

In 2010, the US Food and Drug Administration (FDA) approved a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect after studies in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This medication, however, may be commonly prescribed in patients with dementia and/or Parkinson disease (PD).. To investigate the prescribing patterns of dextromethorphan-quinidine, including trends in associated costs.. This population-based cohort study of patients prescribed dextromethorphan-quinidine used data from 2 commercial insurance databases, Optum Clinformatics Data Mart and Truven Health MarketScan. The Medicare Part D Prescription Drug Program data set was used to evaluate numbers of prescriptions and total reported spending by the Centers for Medicare & Medicaid Services. Patients were included if they were prescribed dextromethorphan-quinidine from October 29, 2010, when the drug was approved, through March 1, 2017, for Optum and December 31, 2015, for Truven. Data were analyzed from December 1, 2017, through August 1, 2018.. The proportion of patients prescribed dextromethorphan-quinidine with a diagnosis of MS, ALS, or dementia and/or PD, as well as the number of patients with a history of heart failure (a contraindication for the drug).. In the commercial health care databases, 12 858 patients filled a prescription for dextromethorphan-quinidine during the study period. Mean (SD) age was 66.0 (18.5) years, 66.7% were women, and 13.3% had a history of heart failure. Combining results from both databases, few patients had a diagnosis of MS (8.4%) or ALS (6.8%); most (57.0%) had a diagnosis of dementia and/or PD. In the Medicare Part D database, the number of patients prescribed dextromethorphan-quinidine increased 15.3-fold, from 3296 in 2011 to 50 402 in 2016. Reported spending by Centers for Medicare & Medicaid Services on this medication increased from $3.9 million in 2011 to $200.4 million in 2016.. Despite approval by the FDA for pseudobulbar affect based on studies of patients with ALS or MS, dextromethorphan-quinidine appears to be primarily prescribed for patients with dementia and/or PD.

Topics: Aged; Amyotrophic Lateral Sclerosis; Dementia; Dextromethorphan; Drug Combinations; Excitatory Amino Acid Antagonists; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Parkinson Disease; Pseudobulbar Palsy; Quinidine; United States; United States Food and Drug Administration