Methylphenidate improves cognition, quality of life in epilepsy patients

By Liz Meszaros, MDLinx
Published March 21, 2018

Key Takeaways

In patients with epilepsy, methylphenidate (MPH) may be both safe and effective and bring about significant improvements in both cognition and quality of life, according to results published in Epilepsia.

Methylphenidate is a central nervous system stimulant approved for the treatment of attention deficit/hyperactivity disorder (ADHD) and narcolepsy. Patients with epilepsy can suffer from inattention, memory impairment, and slower neurologic processing. The use of MPH in patients with concurrent ADHD and epilepsy is controversial due to the possibility that it may lower the seizure threshold.

“Our preceding double-blind, placebo-controlled, single-dose study in this cohort demonstrated positive effects of MPH in patients with epilepsy,1 but data are needed to demonstrate MPH’s safety and efficacy for longer-term use in clinical dosing regimens in adult epilepsy patients with cognitive comorbidities. The present investigation is a 1-month, open-label follow-up to the aforementioned study. We hypothesized that MPH would improve scores on objective cognitive measures and on measures of quality of life without an increased risk of seizures,” noted the study authors, led by Jesse Adams, MD, second-year child and adolescent psychiatry fellow, University of Washington, Seattle, WA.

For this study, Dr. Adams and fellow researchers enrolled 28 patients with epilepsy (mean age: 36.4 years; 13 men) and 14 healthy, nonmedicated controls. Doses of MPH ranged from 20-40 mg/d and were titrated according to clinical practice and patient tolerance. They used the following tests to assess cognition:

  • Conners’ Continuous Performance Test (CPT)
  • Symbol-Digit Modalities Test (SDMT)
  • Medical College of Georgia Memory Test (MCG)

Researchers also tested patients using the Beck Depression Inventory 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale, Stimulant Side-Effect Checklist, Liverpool Adverse Events Profile, Quality of Life in Epilespy-89 (QOLIE-89), and seizure frequency.

Twenty-one patients had focal epilepsy, 6 generalized, and 1 unclassified. Mean duration of epilepsy was 12.3 years, and mean baseline seizure incidence was 2.8 per month.

Researchers found significant improvements in patients treated with MPH on the SDMT, MCG, CPT, and QOLIE, as well as improvements in the BDI-II and additional subscales that were not as significant.

Compared with controls, patients treated with MPH had greater improvement in omissions and commissions. Finally, researchers found that the frequency of seizures was not increased in patients treated with MPH (2.8/month at baseline vs 2.4/month).

In all, 25 patients reached and tolerated the full 20-mg BID dose of MPH. Side effects included anxiety, insomnia, sore throat, reduced appetite, jitteriness, and vivid dreams, all of which either resolved by the end of the study or were considered tolerable by the subjects.

“Taken together, these data suggest that instant-release MPH may be a safe and effective medication for treating cognitive difficulties in adult patients with epilepsy, and that improvement on some cognitive variables was greater than can be explained by test–retest improvement alone,” concluded these researchers.

This study was funded by the Stanford University’s Department of Neurology.


  1. Adams J, Alipio-Jocson V, Inoyama K, et al. Methylphenidate, cognition, and epilepsy: a double-blind, placebo-controlled, single-dose study. Neurology. 2017;31:470–476.

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