Treatment of Multiple Sclerosis–Related Cognitive Problems With Adjunctive Modafinil

In patients with multiple sclerosis (MS), attention and information-processing-speed impairment contribute to dysfunction in other cognitive domains (learning, memory). Treatment for MS-related attention and processing-speed deficits may have dual benefits: improvement of function in these domains and in overall cognitive efficiency. The objective of this study was to determine whether adjunctive treatment of fatigue with modafinil ameliorates deficits in attention and cognitive domains reliant on attention. Relapsing-remitting MS patients receiving intramuscular interferon beta-1a (IM IFNβ-1a) were screened for attention problems with four well-validated, reliable, standardized neurocognitive measures sensitive to attention impairment. Those scoring at least 1 standard deviation below normative expectations on at least two of the measures were eligible for continued participation. Participants with normal values on all physical screening measures were randomized to one of two groups: continued IM IFNβ-1a alone or plus modafinil. Significant mean group differences were found at 4 months on multiple measures of fatigue and cognitive functioning. Patients on combination therapy reported significantly less fatigue (P <.05) and performed significantly better (P <.05) than those in the monotherapy group on measures tapping simple attention span, working memory, and phonemic verbal fluency. Combination therapy was generally well tolerated. No serious adverse events were reported by patients in either treatment arm. This study was developed as a proof of concept that attention-enhancing medications could be used to address fatigue, cognition, and mood in MS patients. The results demonstrate the need for a larger study to determine relative safety and efficacy.