Methylphenidate for Epilepsy-related Cognitive Deficits
This study is looking at whether methylphenidate, a medication approved for ADHD, can help improve memory and thinking problems in adults with epilepsy. Participants will be randomly assigned to receive either methylphenidate or a placebo (sugar pill) for 8 weeks. Neither you nor your doctor will know which you are receiving during this time. After 8 weeks, all participants will have the option to take methylphenidate for another 8 weeks. Researchers will measure changes in attention and memory using specific tests. The study is open to adults aged 18 and older who have focal-onset epilepsy and report cognitive difficulties. The goal is to see if methylphenidate can improve attention in people with epilepsy.
- Study design
- This is a randomized, double-blind study, meaning participants are assigned by chance to either methylphenidate or a placebo, and neither they nor the researchers will know which treatment they are receiving for the first 8 weeks. After this, all participants can choose to take methylphenidate in an open-label phase for another 8 weeks. The study plans to enroll 226 participants.
- What's involved
- Participants will take study pills twice a day for 8 weeks in the first phase, and then have the option to take methylphenidate for another 8 weeks. Cognitive tests will be performed at the beginning of the study, at Week 8, and at Week 16.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for 16 weeks, with cognitive tests at Week 8 and Week 16.
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NCT04419272
Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits
Recruiting
PHASE4Ages 18+InterventionalTreatmentVA Office of Research and DevelopmentGovernment-funded
~226 participants
Updated 2026-04-20 on ClinicalTrials.gov
What's tested:MethylphenidatePlacebo
At a glance
Recruiting sites
4 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change in Conners Continuous Performance Test (CPT), Following Placebo vs. Methylphenidate
Measured over Week 8
Conditions
Where it's being run
4 sites across 4 statesFlorida1
Massachusetts1
New York1
Oregon1
Study leadership
- Beth A Leeman-Markowski, MD · PRINCIPAL_INVESTIGATOR · VA NY Harbor Healthcare System, New York, NY
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age 18 years of age or older;
Capacity to provide informed consent;
Ability to live independently and complete activities of daily living;
Stable seizure frequency at the time of enrollment, such that the subject's treating physician does not believe a change in ASM regimen to be warranted during the trial (ASMs should remain unchanged during the 16 weeks of participation unless absolutely required clinically due an unanticipated change in seizure frequency or severity);
Fluency in written and spoken English. 2. CONTROLS \*DO NOT UNDERGO ANY DRUG OR PLACEBO INTERVENTION Two additional subject groups will be included, to control for effects of repeated testing in the open-label extension phase: healthy subjects and epilepsy patients without cognitive complaints, who will not receive the study drug at any point during the study. Epilepsy patients without cognitive deficits must otherwise meet all of the above criteria.
Age 18 years or older;
Capacity to provide informed consent;
Ability to live independently and complete activities of daily living;
Fluency in written and spoken English.
Exclusion
Psychogenic, non-epileptic spells
Delirium in the past year
Other progressive neurologic illness (i.e., malignant brain tumor). A benign, stable neoplasm with no plans for resection will not be cause for exclusion.
A history of alcohol or illicit drug abuse;
Generalized tonic-clonic or other generalized motor seizure(s) within 48 hours or focal-onset seizures with impaired awareness within 24 hours of neuropsychological testing;
Status epilepticus in the past year;
Neurosurgery within the past 6 months;
Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, more than 1 lifetime suicide attempt, and/or current high-risk suicide flag in the medical record;
Psychotic disorders
Severe anxiety (\>26 on the Beck Anxiety Inventory \[BAI\]) and impulse control disorders;
Untreated sleep disorders;
Use of narcotic or other sedating medications within 6 hours of testing (i.e., diphenhydramine);
Concurrent severe major medical illness (i.e., cancer requiring chemotherapy or resection)
Prior transient ischemic attack (TIA) or stroke
Current pregnancy or pregnancy planned during the trial
Breastfeeding
Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or MAOI use within 14 days of beginning the trial;
Structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or coronary artery disease (including a history of myocardial infarction, cardiac stent placement, coronary artery bypass graft surgery, or angina);
Bipolar disorders;
Concurrent use of medications for erectile dysfunction (e.g., tadalafil, sildenafil);
Use of medications that may lower seizure threshold (e.g., tramadol, bupropion) or induce psychosis (i.e., varenicline);
Known allergy or intolerance to MPH;
Uncontrolled hypertension;
History of seizures, epilepsy, or psychogenic, non-epileptic spells;
Diagnosis of dementia (i.e., Alzheimer's disease), MoCA score of \<26;
Delirium in the past year;
Other progressive neurologic illness (i.e., malignant brain tumor);
Prior moderate or severe traumatic brain injury (TBI);
Mild TBI within the past 6 months;
A history of alcohol or illicit drug abuse;
Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, more than 1 lifetime suicide attempt, and/or current high-risk suicide flag in the medical record;
Psychotic, severe anxiety (BAI \>26), or impulse control disorders;
Untreated sleep disorders;
Use of narcotic or other sedating medications within 6 hours of testing;
Ongoing major neurological or medical illness (i.e., cancer requiring chemotherapy or resection);
Prior TIA or stroke;
What this trial measures
- Change in Conners Continuous Performance Test (CPT), Following Placebo vs. MethylphenidateWeek 8
Conners Continuous Performance Test (CPT) d' value, a measure of attention, compared post-placebo vs. post-methylphenidate (MPH) in a double-blind, parallel group, placebo controlled, randomized design