Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits

Eligibility Criteria

• 1. SUBJECTS WITH EPILEPSY
• * 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.
• * 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;
• * Suicide attempt in the past year and/or 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;
• * Suicide attempt in the past year and/or 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;