Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials

Mao-Hsuan Huang; Bing-Syuan Zeng; Ping-Tao Tseng; Chih-Wei Hsu; Yi-Cheng Wu; Yu-Kang Tu; Brendon Stubbs; Andre F Carvalho; Chih-Sung Liang; Tien-Yu Chen; Yen-Wen Chen; Kuan-Pin Su

doi:10.1016/j.jagp.2023.06.013

Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials

Am J Geriatr Psychiatry. 2023 Dec;31(12):1062-1073. doi: 10.1016/j.jagp.2023.06.013. Epub 2023 Jul 6.

Authors

Mao-Hsuan Huang¹, Bing-Syuan Zeng², Ping-Tao Tseng³, Chih-Wei Hsu⁴, Yi-Cheng Wu⁵, Yu-Kang Tu⁶, Brendon Stubbs⁷, Andre F Carvalho⁸, Chih-Sung Liang⁹, Tien-Yu Chen¹⁰, Yen-Wen Chen¹¹, Kuan-Pin Su¹²

Affiliations

¹ Department of psychiatry (M-HH), Yuanshan and Suao branches of Taipei Veterans General Hospital, Ilan, Taiwan; Division of Psychiatry (M-HH), Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Institute of Biomedical Sciences (B-SZ, P-TT), National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine (B-SZ), E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Institute of Biomedical Sciences (B-SZ, P-TT), National Sun Yat-sen University, Kaohsiung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology (Y-WC, P-TT), Kaohsiung City, Taiwan; Department of Psychology (P-TT), Collage of Medical and Health Science, Asia University, Taichung, Taiwan; Institute of Precision Medicine (P-TT), National Sun Yat-sen University, Kaohsiung City, Taiwan.
⁴ Department of Psychiatry (C-WH), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁵ Department of Sports Medicine (Y-CW), Landseed International Hospital, Taoyuan, Taiwan.
⁶ Institute of Epidemiology & Preventive Medicine (Y-KT), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry (Y-KT), National Taiwan University Hospital, Taipei, Taiwan.
⁷ Department of Psychological Medicine (BS), Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Physiotherapy Department (BS), South London and Maudsley NHS Foundation Trust, London, UK; Positive Ageing Research Institute (PARI) (BS), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK.
⁸ Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre (AFC), School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
⁹ Department of Psychiatry (C-SL), Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences (C-SL), National Defense Medical Center, Taipei, Taiwan.
¹⁰ Department of Psychiatry (T-YC), Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science (T-YC), National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹¹ Prospect Clinic for Otorhinolaryngology & Neurology (Y-WC, P-TT), Kaohsiung City, Taiwan.
¹² Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab) (K-PS), China Medical University Hospital, Taichung, Taiwan; College of Medicine (K-PS), China Medical University, Taichung, Taiwan; An-Nan Hospital (K-PS), China Medical University, Tainan, Taiwan. Electronic address: cobol@cmu.edu.tw.

PMID: 37633762
DOI: 10.1016/j.jagp.2023.06.013

Abstract

Background: The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be supported by small-scale randomized controlled trials (RCTs); however, clinical recommendations might not be conclusive.

Methods: We systematically searched several databases from inception to April 30, 2022, for RCTs of drug therapy in patients with FTD and neuropsychiatric symptoms (primary outcome). Secondary outcomes included changes in caregiver stress, daily interactive activities, cognitive function, and acceptability (adverse event or dropout rates). The network meta-analysis (NMA) procedure was performed under the frequency model, showing effect sizes as standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (95% CIs).

Results: Seven RCTs with 243 participants were included. Compared with placebo, high-dose oxytocin (72 international units) was associated with the greatest improvement in patients' neuropsychiatric symptoms (SMD = -1.17, 95% CIs = -2.25 to -0.08, z = -2.10, p = 0.035). Piracetam significantly worsened neuropsychiatric symptoms (SMD = 3.48, 95% CIs = 1.58 to 5.37, z = 3.60, p < 0.001) and caregiver stress (SMD = 2.40, 95% CIs = 0.80-4.01, z = 2.94, p = 0.003). Trazodone had significantly higher rates of adverse events (OR = 9.53, 95% CIs = 1.85-49.20, z = 2.69, p = 0.007). No pharmacological intervention significantly benefited cognitive function.

Conclusions: This study provides the first NMA for clinical recommendation to support the use of high-dose oxytocin and caution regarding the use of piracetam for neuropsychiatric symptoms in patients with FTD.

Keywords: Drug; major neurocognitive disorder; medication; oxytocin; systematic review.

Publication types

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

MeSH terms

Frontotemporal Dementia* / drug therapy
Humans
Network Meta-Analysis
Oxytocin
Piracetam*
Randomized Controlled Trials as Topic
Treatment Outcome

Substances

Piracetam
Oxytocin