Background
Pseudobulbar Affect (PBA), a common symptom of several neurological conditions including ALS/MND. People affected by PBA experience sudden episodes of unintentional or involuntary crying and laughter without any emotional stimulus. The symptoms can cause embarrassment and it can disrupt daily life.
PBA is caused by damage to the nerve cells in the brain that control emotions. The drug Nuedexta modulates nerve cell activity in the brain, and it was approved to treat PBA in people with ALS/MND in the United States in 2010. Read on to learn more about Nuedexta’s pathway to approval.
| Approved in: | Commercial Name: |
| USA | Nuedexta |
Background
Nuedexta is an oral medication manufactured by Avanir Pharmaceuticals. After its approval in the US, Nuedexta received approval from the European Medicine Agency (EMA) but for commercial reasons, its approval was later withdrawn
How it Works
Nuedexta contains two active ingredients: dextromethorphan hydrobromide (DMX; the active ingredient in cough syrup) and quinidine sulfate. The drug acts on several different proteins throughout the body, and it is unclear exactly how it works to treat PBA. The quinidine component acts to increase the amount of DMX the body can use, but on its own, quinidine may also have beneficial effects that have not yet been discovered.
The dextromethorphan component is thought to activate certain cell receptors, such as sigma-1 receptors, which are critical for activating nerve cells. It may also inhibit receptors that suppress nerve cell activity, such as NMDA receptors. However, it is unclear how these two effects work together to reduce PBA symptoms in people with ALS/MND.
Although scientists do not know exactly how the drug works, Nuedexta has shown efficacy for treating PBA in multiple clinical trials. Since then, researchers have investigated Nuedexta’s potential as a treatment for other motor symptoms such as impaired speech and swallowing.
Nuedexta in Clinical Trials
Researchers must demonstrate the safety and efficacy of a drug before it can be approved for treatment. A randomized, double-blind, placebo-controlled clinical trial is considered the highest standard.
In these trials, participants are randomly assigned to one out of two or more groups. One group will receive a placebo, which does not contain the test drug. Other groups will receive a specific dose of the test drug.
“Double-blinded” means that neither the participants nor the researchers know who receives which treatment (drug vs placebo). This can prevent bias from affecting the results of the study.
Nuedexta underwent several such clinical trials, ultimately leading to US Food and Drug Administration (FDA) approval in 2010.
Study 1:
In the first pivotal clinical trial for Nuedexta, 140 people with ALS/MND and PBA were randomly assigned to one of three groups. Participants in one group received Nuedexta, while the others received either 30 mg of dextromethorphan or 30 mg of quinidine.
The drug was administered twice daily for 28 days and researchers measured peoples’ emotional outbursts on a scale from 7 (no symptoms) to 35 (many symptoms). If someone scores higher than 13 points, they receive a diagnosis of PBA.
In the trial, the people taking Nuedexta experienced lower rates of PBA episodes. They scored an average of 3.5 points lower on the symptom scale than those taking either dextromethorphan or quinidine alone. Participants taking Nuedexta also rated their quality of life and quality of relationships higher than those in the other two groups.
This trial was published in 2004 in Neurology, in an article titled, “Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial.”
Study 2:
In a second randomized, double-blind, placebo-controlled clinical trial, 150 people with multiple sclerosis received a capsule of Nuedexta or placebo, twice daily for 85 days.
The researchers measured changes in PBA symptoms on the same scale as Study 1.
Nuedexta reduced scores by 7.7 points, on average, compared to placebo, which only reduced scores by 3.3 points.
These results were published in 2006 in an Annals of Neurology article titled, “Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.”
Study 3:
In a third clinical trial, researchers compared two different compositions of Nuedexta. A total of 283 people with ALS/MND and PBA were assigned to one of three groups: Nuedexta containing 30 mg of DMX, Nuedextra containing 20 mg of DMX, or placebo. The treatments were administered twice daily for 12 weeks.
After the 12 weeks, participants receiving both compositions of Nuedexta cut PBA episodes by almost half compared to the placebo group. Furthermore, both compositions led symptoms scores to drop by 8.2 points on average, compared to placebo, which only led to a 5.7-point drop. Symptoms were more likely to go away in those who received Nuedexa, and the higher dose led to improved social functioning and mental health.
These results were published in the Annals of Neurology in an article titled, “Dextromethorphan plus ultra-low-dose quinidine reduces pseudobulbar affect.”
Dose and Administration
In its FDA-approved form, one capsule of Nuedexta contains 20 mg of dextromethorphan and 10 mg of quinidine. For treatment of PBA, people take Nuedexta once daily for seven days and then twice daily thereafter.
Reported Side Effects of Nuedexta
Nuedexta is a prescription medication that should be used in consultation with a physician. Common side effects can include diarrhea, dizziness, coughing, vomiting, fatigue, and urinary tract infections. In addition, there are reports of various drug interactions.
Do not take Nuedexta if you are taking MAO inhibitor drugs (e.g. Marplan, Parnate). Individuals with a medical history of certain disorders such as hepatitis, bone marrow depression, or thrombocytopenia may be more likely to experience complications in response to this medication. Therefore, people with ALS/MND should disclose their medical history and other medications to their healthcare team before using Nuedexta.
Current Status
Recently, Nuedexta gained attention for its potential benefits in treating other bulbar symptoms in ALS/MND, such as speech and swallowing impairments.
In 2017, researchers recruited 60 people with ALS/MND for a randomized, double-blind, cross-over clinical trial looking at if the drug could improve speech and swallowing and reduce drooling. People received Nuedexta or a placebo for 28 days then went off the drug for two weeks. Participants then switched treatment groups for another 28 days: the Nuedexta group switched to placebo and the placebo group switched to Nuedexta. The clinical trial showed promising results, but more research is warranted.
The results were published in a study titled, “Enhanced bulbar function in amyotrophic lateral sclerosis: the Nuedexta treatment trial” in Neurotherapeutics.
A clinical trial is currently ongoing to further investigate the effects of Nuedexta on speech and swallowing in people with ALS/MND. People enrolled in this study will receive one Nuedexta capsule daily for 30 days.
Researchers are also investigating whether the drug can be effective at treating depression, bipolar disorder, Alzheimer’s disease, and autism. While clinical trials have shown promising results, Nuedexta is still only approved for the treatment of PBA, and only in the United States.
Disclaimer: Consult with your doctor to determine if Nuedexta is an option for you. Always disclose your medical history, including any drugs, natural supplements, or herbal medicines you are currently using. Your doctor will determine the right plan for your needs.