Symptom Management

Drug Treatment and Cognitive Dysfunction

By Robert E. Godsall, Ph.D.

MS causes widespread demyelination of the central nervous system associated with inflammatory damage. This damage often occurs in an area of the brain known as the white matter region. The white matter region transmits nerve impulses from one part of the brain to another. In MS, such white matter changes are often associated with varying degrees of cognitive dysfunction.

For many years, researchers were unable to accurately characterize these deficits. Consequently, individuals with MS were often stigmatized, as there seemed to be no basis for their cognitive and behavioral changes. Furthermore, medical treatment was very limited, so little hope was offered to the person experiencing these difficulties.

More recently, the advent of the disease modifying drugs has affected the progression of MS. Six medications are now approved for use: interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®), glatiramer acetate (Copaxone®), natalizumab (Tysabri®), and mitoxantrone (Novantrone®). While these medications have been effective in addressing the physical aspects of MS, they have been less effective in addressing the cognitive aspects. Some of the research into the effects of these drugs on cognitive dysfunction has shown limited benefit. Primarily, Avonex appears to have some effect on slowing the rate of decline in processing speed, memory, executive functioning, and visuospatial ability. Betaseron, with 1-3 years of treatment, has also shown some effect in improving memory. But overall, the results have been inconclusive. This has much to do with methodology, or how the research was conducted.

For example, some studies did not use clearly defined diagnostic categories. Others used different tests to measure cognitive function. In other studies, subjects differed in time since presentation of symptoms or time since initial diagnosis. To further complicate this research, the neural mechanisms underlying cognitive changes are still not clearly understood. All of these inconsistencies make it difficult to interpret and apply the results or have any kind of reasonable expectations about treatment.

In an ongoing effort to help their patients, healthcare providers are evaluating the potential benefit of other medications. Many are using donepezil (Aricept®), a medication developed to treat memory problems associated with Alzheimer’s disease. Hopefully, the drug will also improve memory in MS. Another medication being used in MS is memantine (Namenda®), which was also developed to address memory problems for people with dementias, such as Alzheimer’s disease. Because these medications are being used in a patient group that was not included in the clinical trials for development of the drug, this is known as “off-label prescriptive use.” The clinical evidence for success with off-label use is often anecdotal since the drug was not tested in a clinical trial involving MS patients.

Another group of medications, CNS stimulants, are also being prescribed off-label to address MS fatigue, a symptom that can also have a negative impact on cognitive function. CNS stimulants include methylphenidate (Ritalin®), atomoxetine (Strattera®), Adderall®, and more recently, modafinil (Provigil®). Again, because the use of these medications in MS is off-label, the evidence is anecdotal.

The take-home message is two-fold. First, research clearly indicates that early use of the disease-modifying drugs is helpful in slowing the physical effect of MS. While the effect of these drugs is less clear on cognitive symptoms, failure to comply with a treatment regimen will more likely leave you vulnerable to disease progression and possibly, cognitive decline. Second, consider trying the medications in the off-label group. Be sure to discuss the benefits you hope to attain with your physician or nurse practitioner and keep them well informed of your response to the drug.

Rob Godsall, Ph.D., is a clinical neuropsychologist at the MS Institute of Shepherd Center. His primary activities involve patient assessments to determine the impact of MS on cognitive functioning and emotions as well as providing counseling services to MS patients of the Shepherd Center. He lives in Pine Lake, a small community in the Stone Mountain area of Atlanta, where he pursues his love of music, particularly jazz.

(Last reviewed 7/2009)