# Methylphenidate for the treatment of epilepsy-related cognitive deficits: a randomized, double-blind, placebo-controlled trial

> **NIH VA I01** · VA  MEDICAL CENTER · 2024 · —

## Abstract

Objective: The proposed study will determine the efficacy of methylphenidate (MPH) for the treatment of
epilepsy-related attentional dysfunction. Epilepsy patients often have attention and other cognitive deficits,
which can impair quality of life. The causes are typically multifactorial, including frequent seizures, interictal
discharges, brain lesions, and antiseizure medication side effects. The comorbidity of attentional dysfunction
and epilepsy may be partially explained by abnormalities in ascending reticular activating system networks.
There are no FDA-approved medical therapies for epilepsy-related cognitive deficits, and rehabilitation
strategies provide limited benefit. MPH is a stimulant, FDA-approved for the treatment of attention deficit
hyperactivity disorder (ADHD). It is unknown, however, if stimulants would be of benefit for epilepsy-related
cognitive dysfunction. Studies of MPH in children with epilepsy and ADHD suggest efficacy and safety.
Further, large database and registry studies found beneficial effects of MPH on seizure risk in children with
and without epilepsy. Small, single-dose and open label trials of MPH in adults with epilepsy and attentional
dysfunction suggest benefit and safety, but longer-duration, controlled trials with larger numbers of subjects
are needed.
The proposed study is a multi-site, randomized, double-blind, placebo-controlled trial of MPH, with an open-
label extension period, to determine the efficacy of MPH for adult epilepsy-related attentional dysfunction. The
study will also establish the effects of MPH on other attention-dependent cognitive processes ({i.e., a
combined measure of} memory, psychomotor speed, and executive function) and quality of life. The
hypothesis is that subjects will have improved cognitive function and quality of life with MPH compared to
placebo. Secondary analyses will determine the impact of MPH on mood and subjective cognitive abilities,
efficacy over an open-label period, and safety, including effects on seizure frequency.
Research Plan/Methods: Subjects will include {186} adults with epilepsy and self-reported cognitive
deficits, recruited from the Manhattan, Portland, Miami, and Boston VA hospitals. In the blinded phase,
subjects will {be randomly assigned to} receive either placebo or MPH (titrated to 20 mg twice daily) for 8
weeks. Subjects will then receive open-label MPH for 8 weeks (titrated to 20 mg twice daily). Cognitive testing
will be administered at baseline, the end of blinded treatment (Week 8), and the end of the open-label period
(Week 16). The cognitive battery will include tests of attention (Continuous Performance Test), memory (MCG
Paragraph Test), psychomotor speed (Symbol Digit Modalities Test), and a combined measure of divided
attention, psychomotor speed, and response inhibition (Stroop Color Word Interference Test). Additional
measures will include quality of life (Quality of Life in Epilepsy Patient Inventory-89), side effects (Adverse
Ev...

## Key facts

- **NIH application ID:** 10833079
- **Project number:** 5I01CX002474-02
- **Recipient organization:** VA  MEDICAL CENTER
- **Principal Investigator:** Beth Ami Leeman-Markowski
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833079

## Citation

> US National Institutes of Health, RePORTER application 10833079, Methylphenidate for the treatment of epilepsy-related cognitive deficits: a randomized, double-blind, placebo-controlled trial (5I01CX002474-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833079. Licensed CC0.

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