Only 15% of patients prescribed dextromethorphan hydrobromide plus quinidine sulfate had pseudobulbar affect due to multiple sclerosis or amyotrophic lateral sclerosis, the condition for which this drug is labeled, according to an analysis of two national commercial insurance claims databases published online Jan. 7 in.
Conversely, 57% of patients prescribed dextromethorphan-quinidine (Nuedexta) had a diagnosis of Parkinson’s disease or dementia. Furthermore, according to Medicare Part D data, prescriptions for dextromethorphan-quinidine rose 15-fold during a recent 6-year period, with a concurrent 50-fold rise in reimbursement. “In response to findings such as ours, further attention should be paid to educating prescribers about the actual benefits and risks of this costly drug combination,” Michael Fralick, MD, and his associates at Brigham and Women’s Hospital and Harvard Medical School, Boston, wrote in their paper.
The Food and Drug Administration approved Nuedexta in 2010 for the treatment of pseudobulbar affect after it produced modest improvements in laughing or crying episodes in a 12-week, placebo-controlled trial of patients with multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). The initial FDA label noted: “Nuedexta has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.” Then, in 2015, patients with Alzheimer’s disease showed modest improvements in agitation scores when they received dextromethorphan-quinidine in a 10-week, placebo-controlled, industry-designed and sponsored trial. Although the dextromethorphan-quinidine arm also had higher rates of falls, urinary tract infections, and serious adverse events, the prescribing information was updated in 2015 to remove the statement about patients with dementia.
To assess real-world prescribing patterns for dextromethorphan-quinidine, Dr. Fralick and his associates analyzed data from 12,858 patients who filled a prescription for this medication between 2010 and 2017 and were recorded in the Optum Clinformatics Data Mart or Truven Health MarketScan databases. Only 8.4% of patients had a diagnosis of MS and only 6.8% had ALS, while 57% had dementia and/or Parkinson’s disease and 28% had an unknown diagnosis. The number of patients prescribed dextromethorphan-quinidine rose from nearly 3,300 in 2011 to more than 50,000 in 2016, while spending on this medication by the Centers for Medicare & Medicaid Services increased from $3.9 million to $200.4 million during the same time period.
Current treatments for behavioral symptoms of dementia “are largely ineffective, and thus clinicians may want to prescribe dextromethorphan-quinidine to see if it helps their patients,” the researchers wrote. “Yet the absence of data showing efficacy, coupled with the demonstrated risks of falls and possible cardiac effects, calls this strategy into question.
“Further studies should be required to evaluate the safety and effectiveness of this medication as it is currently being used,” the authors suggested.
Study funders included the Laura and John Arnold Foundation, the Harvard Program in Therapeutic Science, the Engelberg Foundation, and the University of Toronto Clinician Scientist Training Program. One author disclosed grants from the Food and Drug Administration Office of Generic Drugs and Division of Health Communication unrelated to the study topic.
SOURCE: Fralick M et al. JAMA Inter Med. 2019 Jan 7.