An oral medicine approved to treat pseudobulbar affect — involuntary outbursts of laughing or crying — in people with amyotrophic lateral sclerosis or multiple sclerosis is most often prescribed to treat those with Parkinson’s disease or dementia, a study based on U.S. health databases reports.
The study “Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect,” published in JAMA Internal Medicine, also noted a higher risk of falls and possible cardiac issues in these older patient groups.
Nuedexta (dextromethorphan-quinidine), by Avanir Pharmaceuticals, was approved to treat pseudobulbar affect (PBA) in ALS and MS patients by the U.S. Food and Drug Administration (FDA) in 2010. PBA refers to sudden, uncontrollable, and often inappropriate episodes of crying or laughing.
Approval was based on results of a Phase 3 clinical trial (NCT00573443) conducted in people with ALS and MS that showed these outbursts were reduced by nearly half among treated patients over 12 weeks compared to those given placebo.
Its initial label noted that Nuedexta was not known to be “safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.” But a 10-week Phase 2 trial (NCT01584440) found its use lowered agitation scores by one or two points in patients with probable Alzheimer’s disease over 10 weeks compared to those on placebo.
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Alzheimer’s patients given the dextromethorphan-quinidine medication also had higher rates of falls and urinary tract infection, but it was “generally well tolerated,” according to a study published in 2015 reporting on that trial. Prescribing information for Nuedexta was updated that same year to remove that initial warning statement.
Extrapolating a therapy’s efficacy and safety to patients who have not been the focus of rigorous research is common but can be clinically challenging, particularly when there is little evidence supporting likely clinical benefit and safety. Because Parkinson’s and dementia patients can experience rapid and exaggerated mood changes, researchers decided to look at prescribing patterns for Nuedexta and changes in prescription and cost trends over time.
Because there has been evidence that Nuedexta is commonly prescribed to patients with dementia and/or Parkinson’s disease, as they can also experience rapid and exaggerated mood changes, researchers examined the medicine’s prescribing patterns and how the prescription and cost trends have changed over time.
They used data from two commercial insurance databases, Optum Clinformatics Data Mart and Truven Health MarketScan, to evaluate the numbers of prescriptions and total reported spending by the Centers for Medicare & Medicaid Services. Data were collected on 12,858 patients given prescriptions from Oct. 29, 2010 (Nuedexta approval date), until Dec. 31, 2015 (most recent data for the Truven database), and March 1, 2017.
Combining results from both databases, the researchers found that only 8.4% of patients prescribed Nuedexta had an MS diagnosis and only 6.8% had one for ALS.
Rather, the majority of patients prescribed Nuedexta — 57.0% — were Parkinson’s or dementia patients. “Our findings suggest that dextromethorphan-quinidine was primarily prescribed for patients with dementia and/or PD,” the study noted.
Additionally, 13.3% of prescribed patients had a history of heart failure, which is a contraindication for the therapy.
A more than 15-fold increase in the number of patients prescribed Nuedexta from 2011 to 2016 — 3,296 to 50,402, respectively – was also found. Likewise, the reported spending by Centers for Medicare & Medicaid Services on Nuedexta increased from $3.9 million in 2011 to $200.4 million in 2016, the study found.
These results show that despite the fact that approval of Nuedexta by the FDA for pseudobulbar affect was based on studies conducted in patients with ALS or MS, the medicine appears to be primarily prescribed for elderly patients with dementia and/or Parkinson’s disease.
“Current therapies to treat behavioral symptoms of dementia are largely ineffective, and thus clinicians may want to prescribe dextromethorphan-quinidine to see if it helps their patients, despite the dearth of trial evidence on its efficacy in this context,” 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.”
Similar to antipsychotics, Nuedexta is also being prescribed to a broader and older patient population than its preapproval study group, the researchers said. “[W]e found that it is being used in a population that is approximately 15 years older than those included in the main preapproval clinical trial (mean ages, 66.0 years compared with 52.0 years). Age is one of the strongest risk factors across all drugs for adverse drug events.”
In light of these findings, the researchers emphasized that further attention needs to be paid to educating physicians about the potential benefits and risks of this medication. They added that the FDA should be more closely monitoring the patient populations using a medication after its approval, and recommended further study of Nuedexta in people with Parkinson’s and dementia.
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