Avanir Pharmaceuticals announced positive results from a Phase III clinical trial evaluating the safety and effectiveness of the oral drug Neurodex^TM (a combination of dextro­methorphan and quinidine sulfate) for treating the symptom of “pseudobulbar affect,” a condition involving uncontrollable laughing and/or crying affecting a small proportion of persons with MS and some other disorders, such as ALS, Alzheimer’s disease and stroke.
In a press release issued August 24, 2004, the company reports that it intends to apply to the U.S. Food and Drug Administration for approval to market the drug for pseudobulbar affect based on the results of this and another trial that studied patients with ALS.

Avanir has not yet published the data from the MS trial, but provided an outline of the results in its press release. According to the press release, 150 individuals at 22 clinical sites, who had MS and a history of pseudobulbar affect, received either oral Neurodex or inactive placebo every 12 hours for 90 days. Those on treatment experienced a statistically significant reduction in a clinical score (the Center for Neurologic Study Lability Scale) that measures the frequency and severity of episodes of pseudobulbar affect, the primary endpoint examined in the study. Secondary endpoints indicated that the drug reduced the number of episodes, improved quality of life and quality of relationships, and reduced pain. Side effects were tolerable, with dizziness being the primary complaint in some who received the active treatment.

“The availability of a drug that could safely and effectively treat pseudobulbar affect would be a real breakthrough for those with MS and other neurological conditions who experience this troubling symptom,” said Dr. Nicholas LaRocca, a clinical psychologist who directs the National MS Society’s research programs in patient management and health care delivery and policy.

Multiple sclerosis involves an immune-system attack against the central nervous system – the brain, spinal cord and optic nerve. The cause of pseudobulbar affect in MS is thought to be related to disease-induced tissue damage in areas of the brain involved in emotional expression. The exact number of  persons with MS who have pseudobulbar affect is not known, but some estimates suggest about 10%.

There is currently no drug approved specifically for treating pseudobulbar affect. The prime ingredient of Neurodex is dextromethorphan, a cough suppressant used in many over-the-counter cough and cold remedies. Neurodex is a combination of this ingredient with an enzyme inhibitor, quinidine, which seems to help sustain levels of dextromethorphan in the body. Neurodex is not currently approved for use outside of clinical studies, and has not yet been reviewed by the FDA for safety and efficacy against the symptom of pseudobulbar affect. 

Individuals experiencing this symptom should consult their physicians to discuss treatment options which may include other drugs as well as counseling to assist them and their families to cope with this problem. A Clinical Bulletin providing details about pseudobulbar affect and its treatment in MS is available on the National MS Society’s Website.

http://www.nationalmssociety.org/research-2004aug25.asp