Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

OBJECTIVE

To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy.

METHODS

This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere.

RESULTS

Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect.

CONCLUSIONS

This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required.

CLINICALTRIALSGOV IDENTIFIER

NCT02178995.

CLASSIFICATION OF EVIDENCE

This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints.