TY - JOUR T1 - Early use of donepezil against psychosis and cognitive decline in Parkinson’s disease: a randomised controlled trial for 2 years JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1332 LP - 1340 DO - 10.1136/jnnp-2018-318107 VL - 89 IS - 12 AU - Hideyuki Sawada AU - Tomoko Oeda AU - Masayuki Kohsaka AU - Atsushi Umemura AU - Satoshi Tomita AU - Kwiyoung Park AU - Kouichi Mizoguchi AU - Hidenori Matsuo AU - Kazuko Hasegawa AU - Harutoshi Fujimura AU - Hiroshi Sugiyama AU - Michikazu Nakamura AU - Seishi Kikuchi AU - Kenji Yamamoto AU - Toshiaki Fukuda AU - Suminobu Ito AU - Masashi Goto AU - Kosuke Kiyohara AU - Takashi Kawamura Y1 - 2018/12/01 UR - http://jnnp.bmj.com/content/89/12/1332.abstract N2 - Objectives Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson’s disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients.Methods A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson’s Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping.Results Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11–0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers.Conclusions Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil.Trial registration number UMIN000005403. ER -