A comprehensive review of pharmacologic agents used in the treatment of multiple sclerosis (MS) was conducted by researchers at Kessler Foundation to seek efficacy evidence for the cognitive dysfunction experienced by more than half of affected individuals.

The researchers identified 87 articles using the PubMed and PsycINFO databases and the 2017 American Academy of Neurology (AAN) criteria for therapeutic trials. Further, standardized effect sizes were calculated for comparison across trials.

The following therapeutic categories were represented: Disease-modifying therapies (DMTs), interferon B-1a, B1b, glatiramer acetate, natalizumab, fingolimod; symptomatic therapies such as dalfampridine; cognition enhancers: rivastigmine, Gingko biloba, donepezil; stimulants such as modafinil, armodafinil, methylphenidate, amphetamine sulfate, amantadine; and other therapies that were neither DMTs nor stimulants, such as estrogen, methylprednisolone, simvastatin, human erythropoietin.

The review of the studies of DMTs failed to support the efficacy for treating cognitive deficits, with a majority of class 3 and 4 evidence, according to the study authors.

“We found no class 1 evidence, and class 2 evidence was minimal to none,” said Michelle H. Chen, PhD, postdoctoral fellow in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation, in a press release.

There were contradictory findings, although most of the studies of symptomatic therapies were randomized controlled trials with primary cognitive outcomes, according to the study authors. The findings show inconclusive evidence for the cognitive efficacy of symptomatic therapies. Studies of the agents in the “other” category also found insufficient evidence to support their use to treat cognitive problems.

In conclusion, there was insufficient evidence for cognitive efficacy across the spectrum of pharmacologic agents used in the treatment of MS, according to the study authors.

“Given the impact of cognitive dysfunction on individuals with MS, it is prudent to explore the potential for cognitive efficacy of available pharmaceuticals,” said Helen Genova, PhD, in a press release.

Future studies involving DMTs must focus on cognitive outcomes and follow standardized criteria such as the AANs, according to the study authors.

“Randomized, controlled studies with cognition as the primary outcomes will provide clinicians with the information they need to choose for optimal treatments for patients,” Genova said in a press release.

Evidence lacking for drug treatment of multiple sclerosis-related cognitive impairment. https://kesslerfoundation.org/press-release/evidence-lacking-drug-treatment-multiple-sclerosis-related-cognitive-impairment. Published June 17, 2020. Accessed June 19, 2020.