A Cough Medicine and Neurologic Disorders
Can a common cough medicine contribute to effective treatment of symptoms in persons with neurologic disorders? The evidence is mounting in its favor. At the recent American Academy of Neurology annual meeting, research results were presented from a phase 3, double-blind, placebo-controlled, multicenter study into the safety and efficacy of a dextromethorphan/quinidine capsule in treating pseudobulbar affect (PBA) in patients with multiple sclerosis.
The study involved 150 patients, with 76 receiving the dextromethorphan/quinidine capsule (Neurodex, Avanir Pharmaceuticals) and 74 receiving placebo. Patients treated with Neurodex reported 46% fewer laughing and/or crying spells during the 3-month trial--and improvement was seen during the first week, according to Hillel D. Panitch, MD, a professor of neurology at the University of Vermont, who presented the results. Panitch said the primary end point of the 3-month study, a change in the Center for Neurological Study Lability Scale score, was statistically achieved in the form of a 7.7% decrease in PBA symptoms for patients who received Neurodex, compared with a 3.3% decrease in PBA symptoms for patients who received placebo (P < .0001).
Avanir filed a new drug application last December for Neurodex for treating PBA. Those efforts sparked the writing of a news article that included both critics and supporters (Pollack A. Marketing a disease, and also a drug to treat it. New York Times, May 9, 2005:C1).
Critics said that PBA is not a condition that warrants drug therapy because patients with it are fighting more serious health problems and because PBA has a variety of names that could confuse patients and doctors. "They don't need to be treated; they don't ask to be treated," leading researcher in amyotrophic lateral sclerosis (ALS) Vincent Meininger, MD, professor of neurology at the Hôpital de la Salpêtrière, Paris, was quoted as saying. He was countered by Panitch in the article: "It's socially disabling and people tend to hide it, which is one reason you don't hear much about it."
Neurodex also has been tested successfully as a treatment for PBA in patients with ALS (Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine. Neurology. 2004;63:1364-1370). Avanir plans to begin a phase 3 trial this year to test it as a treatment for diabetic neuropathic pain.
Meanwhile, the over-the-counter version of dextromethorphan may help patients with fibromyalgia calm their nerves that turn ordinary touches into agonizing pain, according to University of Florida researchers (Staud R, Vierck CJ, Robinson ME, Price DD. Effects of the N-methyl d-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in patients with fibromyalgia and normal control subjects. J Pain. 2005;6:323-332). However, the researchers cautioned against having patients self-medicate with the cough syrup because side effects could occur.
Recent FDA Activities
Restless Legs Syndrome On May 5, ropinirole (Requip, GlaxoSmithKline) became the first and only FDA-approved drug treatment for moderate to severe primary restless legs syndrome (RLS). The FDA based its approval on 3 randomized, double-blind, placebo-controlled studies in adults. The agent was approved for treatment of Parkinson disease in 1997. Ropinirole is a second-generation dopamine agonist.
According to a review published in January, clinical studies indicate that ropinirole reduces the motor symptoms of RLS and improves overall sleep quality (Kakar RS, Kushida CA. Ropinirole in the treatment of restless legs syndrome. Expert Rev Neurother. 2005;5:35-42).
MRIs and Neurostimulators The FDA issued on May 10 a public health notice for radiologists and physicians to take preventive action against potential injury or death in patients with implanted neurologic stimulators who undergo MRI procedures. The agency said it had received "several reports of serious injury, including coma and permanent neurological impairment," that appeared to be associated with the combination of implanted neurostimulators and MRI.
The FDA's recommendation to physicians is: "Explain to the patient what MRI procedures are and stress that they must consult with the monitoring physician before having any MRI exam to find out whether it can be performed safely." The topic was investigated last year in an article by a team that included Frank G. Shellock, PhD, adjunct clinical professor of radiology at the Keck School of Medicine, University of Southern California, and the head of the Institute for Magnetic Resonance, Safety, Education, and Research (www.MRIsafety. com) in Los Angeles (Rezai AR, Phillips M, Baker KB, et al. Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. Invest Radiol. 2004;39:300-303).
News From Recent Reports
Attention-Deficit Hyperactivity Disorder Researchers at the University at Buffalo in New York have found that children with attention-deficit hyperactivity disorder (ADHD) respond positively when behavior modification therapy is combined with drug treatment in the form of a methylphenidate patch (MethyPatch, Shire Pharmaceutical Group). In an article appearing in the May issue of Experimental and Clinical Psychopharmacology, the researchers, led by William E. Pelham, Jr, PhD, a professor of psychology at the University at Buffalo School of Medicine and Biomedical Sciences, wrote that not only is the combination of therapies effective, the amount of medication used can be reduced by two thirds, compared with use of medication alone.
The study, which included 27 children with ADHD, compared treatment with behavior modification, the MethyPatch, and placebo. Both the patch and behavior modification were effective, but a regimen that combined these therapies produced the best results, according to the researchers. MethyPatch is a new formulation of the stimulant marketed in pill form as Ritalin (Novartis) and Concerta (Eli Lilly). Developed by Noven Pharmaceuticals, MethyPatch was licensed to Shire Pharmaceuticals Group last year. Shire is expected to seek FDA approval of the patch next year, according to a statement from the University at Buffalo.
Depression and Chronic Pain A new study by researchers at the University of Michigan Health System and the University of Cologne, Germany, concludes that depression and chronic pain, while often seen together in patients, should be treated as 2 disorders (Giesecke T, Gracely RH, Williams DA, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum. 2005;51:1577-1584). Using functional MRI (fMRI) and sensory testing, investigators studied how symptoms of depression and clinically diagnosed major depressive disorder affected pain processing in the brains of patients with fibromyalgia. The study involved 53 patients with fibromyalgia and 42 controls. The findings suggest that parallel, independent neural pain-processing networks exist for sensory and affective pain elements. In the fibromyalgia patients, less contact pressure was required to activate neurons associated with acute pain than in controls. According to Daniel J. Clauw, MD, who led the Michigan researchers, this is the first study in which fMRI scans show that pain and depression should be treated independently. According to the published paper, "The implication for treatment is that addressing an individual's depression [eg, by prescribing an antidepressant medication that has no analgesic properties] will not necessarily have an impact on the sensory dimension of pain."