The U.S. Food and Drug Administration (FDA) has approved Nuedexta for "pseudobulbar affect" (PBA), a neurologic condition that sometimes occurs in people with amyotrophic lateral sclerosis (ALS) and involves episodes of involuntary emotional expression out of proportion to or distinct from the person's actual emotional state. The approval was announced by Nuedexta's developer, Avanir Pharmaceuticals, Oct. 29, 2010. (See Nuedexta Is First and Only FDA-Approved Treatment for Pseudobulbar Affect.)
Nuedexta is a combination of two drugs: dextromethorphan hydrobromide (20 milligrams) and quinidine sulfate (10 milligrams). Dextromethorphan acts in the central nervous system to reduce the frequency of unwanted episodes of laughing or crying, although the precise mechanism by which it works is unknown. Quinidine increases blood levels of dextromethorphan by interfering with its breakdown in the body.
A phase 3 trial of Nuedexta (former versions of which were known as Neurodex, Zenvia and AVP923) included approximately 300 participants with PBA secondary to either ALS or multiple sclerosis (a disorder not covered in MDA's program). The investigators found the drug reduced the number of episodes of unwanted laughing or crying compared to a placebo and that it was generally safe and well tolerated for 12 weeks.
During the phase 3 trial, participants took capsules containing 30 milligrams of dextromethorphan plus 10 milligrams of quinidine or capsules containing 20 milligrams of dextromethorphan plus 10 milligrams of quinidine twice daily.
At the end of the phase 3 study, participants were invited to take the 30-milligram capsules on an open-label basis for an additional 12 weeks, during which time the drug continued to demonstrate benefit and safety. (See Zenvia Improves Emotional Symptoms in ALS and Trial results announced for drug for laughing/crying jags.)
The FDA has now approved the formulation that includes 20 milligrams of dextromethorphan and 10 milligrams of quinidine, with a recommendation for a starting dose of one capsule daily by mouth for seven days and one capsule every 12 hours after that, according to information posted on Avanir's website. (See Nuedexta.)
The drug is indicated for people with PBA secondary to ALS or multiple sclerosis and has not been shown to be safe or effective in emotional expression abnormalities that occur in association with Alzheimer's disease or other forms of dementia.
Nuedexta should not be taken in combination with other drugs that contain quinidine or related compounds; nor should it be taken by people on antidepressant drugs known as monoamine oxidase inhibitors (MAOIs) or people with certain cardiac problems.
PBA occurs when neurologic diseases damage the area of the brain that controls expression of emotion. The damage can trigger episodes of involuntary laughing or crying that are completely unrelated to the person's circumstances or are more exaggerated than the person's actual mood would cause.
PBA episodes are unpredictable and can cause embarrassment and withdrawal from social situations.
Meaning for people with ALS
Although Nuedexta does not treat the life-disrupting symptoms of ALS that cause weakness of the muscles associated with speaking, breathing or body movement, it may help control some of the other symptoms of ALS that have an impact on quality of life. The ability to choose what emotions one portrays, particularly in public, is important to many people, and Nuedexta appears to help re-establish this control.
Now that the FDA has approved the drug for use in people with PBA caused by ALS, it should be available soon for physicians to prescribe.
People considering taking Nuedexta should discuss their current health problems and medications, as well as the possible benefits and risks of this new drug, with their physicians.