Intervention: Methylphenidate
Trial phase: Phase 4
ATC code: N06BA04 | N06BA11 | N06BA15
SMILES: COC(=O)C(c1ccccc1)C1CCCCN1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 5
Group description: Participants will receive three single doses of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and will complete cognitive testing and neuropsychiatric questionnaires. This single-dose phase will be followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy will first receive blinded, single-dose capsules in the following order:

10mg of methylphenidate, 20mg of methylphenidate, Placebo.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.
Eligibility criteria:
Inclusion Criteria:

For participants with seizures:

H/o seizures of any cause
Subjective cognitive complaints
Stable antiepileptic drug doses which are not expected to change during the study
Recent normal cardiac auscultation (may be done prior to enrollment by personal physician or study staff)
Neurologist's judgement that participant is clinically appropriate for this study

For healthy volunteers

No history of seizures or other neurological disorders
No history of cognitive complaints for any reason (including ADHD)
Not on any medications which would interfere w/ cognitive testing
English fluency

Exclusion Criteria:

IQ
History of an adverse reaction to methylphenidate
Age >65 or <18

Personal medical history of

Arrhythmias,
Structural cardiac disease,
Other cardiac abnormality
Uncontrolled hypertension (>150/95) during study. For those with BP >140/90 & <150/95, they will be monitored during the study and refer them for treatment if their BP remains elevated throughout the study.
Uncontrolled tachycardia during study
Progressive neurological disorders which may interfere w/ cognition for reasons other than seizures
Glaucoma
Other medical or neurological illnesses or symptoms which may interfere with cognition or medication (e.g., severe liver or renal disease, active infections, etc), or which make use of the medication inappropriate (e.g., severe agitation/anxiety).
Intellectual disability sufficient to render a participant unable to consent
Status epilepticus within the last year
Neurosurgery which would be expected to interfere with study tasks within the last 6 months.

Substance use history

Met criteria for substance use disorder within the past year
Active illicit substance use
Alcohol use meeting criteria for substance abuse
Unwillingness to abstain from alcohol w/in 24 hours of testing

Personal psychiatric history

History of a primary psychotic disorder, such as schizophrenia, or mania.
History of suicide attempts within the last year
Active suicidality
Severe cognitive impairments (e.g. aphasia) which render a participant unable to consent
Currently receiving medications which would be expected to interfere with the study tasks, if they cannot be held for study visits;
Pregnancy or active breastfeeding;
Women of childbearing potential who are sexually active and not willing or able to use a contraceptive strategy during the course of the study.
Any other factor which may interfere w/ a participant's ability to consent or to complete the required cognitive tasks, or may significantly interfere with their performance on the required tests
Concomitant use of an MAOI (if receiving methylphenidate during this study), or use of an MAOI within the last 14 days prior to receiving methylphenidate.