Methylphenidate, cognition, and epilepsy: A 1‐month open‐label trial. (9th October 2017)

• Record Type: Journal Article
• Authors: Adams, Jesse; Alipio‐Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford J.
• Is Part Of: Epilepsia. Volume 58:issue 12(2017)
• Page Start: 2124
• Page End: 2132
• Publication Date: 2017-10-09
• Subjects: Methylphenidate -- All epilepsy/seizures -- Antiepileptic drugs -- Memory -- Attention -- Quality of life; Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.13917
• Languages: English
• ISSNs: 0013-9580

Abstract

Summary: Objective: Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well‐validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention‐deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open‐label follow‐up to a double‐blind, placebo‐controlled, single‐dose study. Methods: Thirty epilepsy patients entered a 1‐month open‐label methylphenidate trial after a double‐blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20–40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol–Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI‐II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side‐Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy‐89 (QOLIE‐89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Results: Twenty‐eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20–60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d′] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI‐II and additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d′ and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month). Significance: Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double‐blind, placebo‐controlled clinical trials are needed.