Rivastigmine for Cognitive Impairment in Multiple Sclerosis: A Prospective Randomized Open Label study with Blinded End-Point Assessment.

Background and Objective:Nearly 40-65% patients with MS develop cognitive impairment during the disease. There is no treatment clearly effective in improving the cognitive deficits. To evaluate the efficacy and safety of Rivastigmine in cognitively impaired MS patients. Materials and Methods:This was a parallel group randomized open label study with blinded end-point assessment. The patient allocation to treatment and control arm was done by telephonic contact with an independent statistician who used a computer to generate a random sequence of allocation using permuted block randomization (varying block size of 4 and 6) in 1:1 ratio. The outcome assessor was blinded to this allocation. A total of 60 patients were in included in the study (30 in each arm). Primary outcome was improvement in memory functions (using logical memory subset of Wechsler Memory Scale III, India) assessed after 12 weeks. Secondary outcomes included fatigue, depression, and safety. Results:In modified intention to treat analysis (N = 22), treatment arm showed statistically significant improvement in memory function with mean difference of 7.56 [95% CI (0.67,14.46), p 0.032] as compared to control arm. There was no statistically significant difference in outcomes such as fatigue and depression. Vomiting was the most common side effect. No major adverse events were observed in either group. Conclusion:Rivastigmine is safe and effective in improving memory functions in cognitively impaired MS patients. However, our study has a small sample size and tested only a single domain. Larger studies with a validated single comprehensive neuropsychological test are needed.