Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index
Chunsoo Lee1, Kyungsang Lee, Hyewon Yu
1From the *Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine; †Statistical Team, C&R Research; ‡Department of Psychiatry, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul; §Department of Psychiatry, Konkuk University Chungju Hospital, Konkuk University School of Medicine, Chungju; ∥Department of Psychiatry, Korea University Medical Center, Korea University College of Medicine; ¶Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine & SMG-SNU Boramae Medical Center, Seoul; #Department of Psychiatry, Pusan National University Hospital, Pusan National University School of Medicine, Busan; **Department of Psychiatry, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon; ††Department of Neuropsychiatry, Seoul National University Bundang Hospital, and Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences; ‡‡Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine; §§Department of Psychiatry, Asan Medical Center, University of Ulsan, College of Medicine, Seoul; ∥∥Department of Psychiatry, Wonkwang University College of Medicine, Iksan; ¶¶Department of Psychiatry, Inha University College of Medicine, Incheon; ##Department of Psychiatry, Jeju National University School of Medicine, Jeju; ***Department of Psychiatry, School of Medicine, Chungnam National University, Daejeon; †††Department of Psychiatry, Kyungpook National University School of Medicine, Daegu; ‡‡‡Department of Psychiatry, Hwasun Chonnam National University Hospital, Hwasun; §§§Department of Psychiatry, Inje University School of Medicine and Paik Institute for Clinical Research, Busan; ∥∥∥Department of Psychiatry, Gyeongsang National University School of Medicine, Chinju; ¶¶¶Center for Clinical Research, Samsung Biomedical Research Institute, Seoul; ###Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Korea; and ****Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC.
Purpose/Background:
Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population.
Methods/Procedures:
To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m).
Findings/Results:
Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002).
Implications/Conclusions:
In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.
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