An experimental medication is showing promise for a condition associated with multiple sclerosis and certain neurological disorders. Results of a clinical trial testing the efficacy of the medicine, known currently by its scientific code AVP-923, were released at the annual meeting of the American Academy of Neurology in Miami Beach last week.1
Uncontrolled Emotions Erupt
The condition the drug is designed to treat is known as pseudobulbar affect (soo-doe-BOWL-bar uh-fekt). In MS, it's believed the body's immune system abnormally strikes tissue in the central nervous system. This fatty tissue is known as myelin, which protects nerve endings in the brain and spinal cord and helps them communicate with each other. When myelin is stripped away in an autoimmune attack, it leaves the nerve endings bare and vulnerable, unable to conduct electrical impulses in their normal way.2
Subsequently, brain lesions occur, and they can cause pseudobulbar affect in some people. People with this condition laugh or cry uncontrollably for no reason and they find it difficult to stop. They know that their emotions don't correlate with a given situation, but they can't help themselves. This condition also occurs in other brain conditions like stroke, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS)—also known as Lou Gehrig's disease.
There is currently no approved therapy to treat pseudobulbar affect. However, antidepressants may be prescribed even though the condition is regarded as a clearly distinguishable pathology from depression.3
Comparative Analysis
In the trial of 150 people with MS, Hillel Panitch, MD, of the University of Vermont College of Medicine in Burlington, Vermont compared outcomes using AVP-923 versus that of placebo. The drug is a combination of dextromethorphan hydrobromide (dex-troh-meh-THOR-phan hye-droh-BROH-mide) and quinidine (KWIN-uh-deen) sulfate. The study ran for 12 weeks. While they were taking medication or placebo during this period, the patients also kept diaries tracking the number of laughing or crying episodes that they experienced each day, as well as any side effects. Each patient was also evaluated at four clinic visits throughout the study.
At the conclusion of the 12-week trial period, Panitch's team discovered AVP-923 had positive effects. They found that 84 percent of the patients taking the medication had improvements in the condition, compared to less than half of those taking only a placebo. The patients in the treatment group also reported overall improvement in their quality of life, quality of their relationships, and amount of pain they experienced during the study.
There was one negative finding: more patients taking AVP-923 reported dizziness than those taking placebo.
"This is the first drug designed specifically for this condition," said Panitch, who is a professor of Neurology and director of the Clinical Trials Unit at the University of Vermont. "The only treatment [available] now is antidepressants, which can have unpleasant side effects."
He says the therapy showed improvements in the patients taking it during his study as early as the first week.
The study was funded by Avanir Pharmaceuticals, which is developing AVP-923.
Other Analyses of the Drug
Similar research was conducted last year testing the efficacy of AVP-923 with its components in a group of people with pseudobulbar affect related to ALS.4 In the randomized, double-blind, controlled trial, AVP-923 was given twice per day for nearly a month, and was compared to a group of patients taking dextromethorphan hydrobromide alone or a group given quinidine sulfate alone.
Each patient was then evaluated three times throughout the study.
At the end of 1 month of treatment, more patients taking AVP-923 experienced symptom improvement compared to the groups given dextromethorphan hydrobromide or quinidine sulfate. Those in the AVP-923 group also reported greater improvements in their quality of life and quality of relationships, the investigators at the University of Wisconsin reported.
"Adverse events were mostly mild or moderate; treatment-related discontinuation was 24% for AVP-923, 6% for dextromethorphan hydrobromide, and 8% for quinidine sulfate," the authors reported.
Despite that, the therapy caused "fewer episodes of crying and laughing, and improvements in overall quality of life and quality of relationships," they wrote.
1. American Academy of Neurology 57th Annual Meeting. 2005 Apr 9-16. Miami Beach, FL.
2. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp.
3. Avanir Pharmaceuticals. Pseudobulbar Affect. Available at: http://www.pseudobulbar.com/background.html#q6. Accessed April 14, 2005.
4. Brooks BR, Thisted RA, Appel SH et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004 Oct 26;63(8):1364-70.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
