Treatment Efficacy and Acceptabilityof Pharmacotherapies for Dementia with Lewy Bodies: A Systematic Review and Network Meta-Analysis

Che-Sheng Chu; Fu-Chi Yang; Ping-Tao Tseng; Brendon Stubbs; Aarsland Dag; Andre F Carvalho; Trevor Thompson; Yu-Kang Tu; Ta-Chuan Yeh; Dian-Jeng Li; Chia-Kuang Tsai; Tien-Yu Chen; Manabu Ikeda; Chih-Sung Liang; Kuan-Pin Su

doi:10.1016/j.archger.2021.104474

Treatment Efficacy and Acceptabilityof Pharmacotherapies for Dementia with Lewy Bodies: A Systematic Review and Network Meta-Analysis

Arch Gerontol Geriatr. 2021 Sep-Oct:96:104474. doi: 10.1016/j.archger.2021.104474. Epub 2021 Jul 2.

Authors

Che-Sheng Chu¹, Fu-Chi Yang², Ping-Tao Tseng³, Brendon Stubbs⁴, Aarsland Dag⁵, Andre F Carvalho⁶, Trevor Thompson⁷, Yu-Kang Tu⁸, Ta-Chuan Yeh⁹, Dian-Jeng Li¹⁰, Chia-Kuang Tsai², Tien-Yu Chen⁹, Manabu Ikeda¹¹, Chih-Sung Liang¹², Kuan-Pin Su¹³

Affiliations

¹ Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
² Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
³ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
⁴ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; Institute of Psychiatry, King's College London, UK.
⁵ Centre for Age-related Medicine, Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway.; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK.
⁶ Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
⁷ School of Human Sciences, University of Greenwich, London, UK.
⁸ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁹ Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
¹⁰ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
¹¹ Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
¹² Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: lcsyfw@gmail.com.
¹³ Institute of Psychiatry, King's College London, UK; Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobolsu@gmail.com.

PMID: 34256210
DOI: 10.1016/j.archger.2021.104474

Abstract

Introduction: We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms (NPS), cognitive function, motor symptoms, and acceptability.

Methods: Electronic databases were searched from inception through June 5, 2019, for randomized controlled trials (RCTs) and open-label trials (OLTs) in patients with DLB. We performed a pairwise conventional meta-analysis (PWMA) and network meta-analysis (NMA) within a frequentist framework. The main outcomes were mean change scores in NPS, general cognition, motor symptoms and acceptability. The effect sizes and odds ratios with 95% confidence intervals (CIs) were calculated. This study was registered with PROSPERO (CRD42018096996).

Results: In total, we included 29 studies (9 RCTs and 20 OLTs). In the NMA with 9 RCTs, both high- (mean difference [MD] 2.00, 95% CIs, 0.69 to 3.31) and low-dose (1.86, 0.58 to 3.15) donepezil were associated with a greater cognitive improvement than placebo. High-dose zonisamide was associated with greater motor symptom improvement ( -4.10, -7.03 to -1.17]). No medications reached statistical significance regarding improving neuropsychiatric symptoms or developing intolerable adverse effects as compared to placebo. In the second NMA, with 29 studies as an exploratory analysis, aripiprazole and yokukansan may be effective for neuropsychiatric symptoms, while levodopa may be associated with cognitive impairment.

Conclusions: We report the most comprehensive evidence for the selection of pharmacotherapy for treating different clusters of DLB-related symptoms. Due to the limited availability of RCTs on DLB, more well-conducted RCTs are needed for MMA to warrant clinical efficacy in the future.

Keywords: Cognitive function; Dementia with Lewy bodies; Lewy body disease; Meta-analysis; Neuropsychiatric symptoms.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Cognition
Humans
Lewy Body Disease* / drug therapy
Network Meta-Analysis
Treatment Outcome