Abstracts

This abstract has been invited to present during the Clinical Research platform session

Rationale: We have previously demonstrated high prevalence of sleep and cognitive disturbances in temporal lobe epilepsy (TLE), as well as the relationship between these. Based on few published reports, donepezil can potentially have some positive effects on REM sleep and cognitive performance in patients with epilepsy, and zolpidem clearly improves slow wave sleep (SWS), while its effects on cognition are not known. This study was aimed at evaluating effects of donepezil vs. zolpidem, compared to placebo, on sleep architecture and cognition in patients with TLE. 

Methods: This study was conducted following approval from the institutional Ethics committee. Consecutive consenting patients with TLE (diagnosed by an epileptologist, through clinical, video-EEG, imaging data), without any severe co-morbidities, were included and randomized into three intervention groups (1- donepezil (10 mg) qAM + bedtime placebo, 2 - placebo qAM+ bedtime 6.25 mg zolpidem, 3 – placebo qAM + bedtime placebo). Randomization and concealment through labelling of boxes containing medication supply, according to computer-generated study codes, was ensured by biostatistics collaborators. Participants underwent epilepsy, sleep (clinical [Pittsburgh Sleep quality index (PSQI) and overnight polysomnography [PSG]), cognition (Wechsler memory scale, trail making test, Western aphasia battery) and quality of life (QOLIE-89) evaluation at baseline and after 6 months of receiving allocated intervention. Change in cognition and PSG parameters, their correlation and QOLIE-89 were analysed.

Results: Among 119 eligible participants, data from 108 (36 in each group), similar at baseline (average age 25.4±8, 27.1±11, 27.6±9 years; sex distribution [% males] 63, 72, and 63 in groups 1, 2, and 3 respectively in the 3 groups), was available for analysis (Figure 1). In group 1 (donepezil group), significant improvement was observed in REM sleep percentage, language and executive function scores at 6-month follow up. In group 2 (zolpidem group), significantly favorable N3 sleep percentage, sleep onset latency as well as both verbal and visual memory scores were observed. Strong correlation was observed between baseline to 6-month change in REM sleep percentage with change in language and executive function scores; and between baseline to 6-month change in N3 sleep percentage and change in verbal memory and executive function scores. Subjective sleep quality (PSQI scores) improved at 6-month follow up, in group 2. No significant change in QOLIE-89 scores was observed.

Conclusions: This double-blind randomized controlled study found significant objective improvement in REM sleep and language scores in patients with TLE receiving donepezil; and in slow-wave-sleep and memory scores in those receiving zolpidem.

Funding: This study was funded by a Department of Health Research, Government of India research grant# I-958. Clinical trial registration number CTRI/2017/04/008359. The authors sincerely acknowledge the contributions of Jyoti Katoch, Sumit Kushwaha, and Mohammed Afsar.