Efficacy of methylphenidate for the treatment of apathy in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled studies.

Min-Hsiang Chuang, Wen-Wen Tsai, Chia-Wei Lee, Jui-Yi Chen, Ching-Chung Ko, Cheuk-Kwan Sun, Kuo-Chuan Hung

Journal: Psychopharmacology 2022;239(12):3743-3753

PMID: 36243827

Abstract

RATIONALE

Despite the reported efficacy of methylphenidate (MET) against Alzheimer's disease (AD)-associated apathy, a recent larger clinical trial was not included in pooled analysis.

OBJECTIVES

This study aimed at investigating the efficacy of MET for attenuating apathy in patients diagnosed with AD.

METHODS

The PubMed, Cochrane Library, and EMBASE databases were searched from inception until March, 2022 to identify randomized controlled trials (RCTs). The primary outcome was apathy improvement assessed with the Neuropsychiatric Inventory (NPI) apathy subscale, Apathy Evaluation Scale (AES), or Clinical Global Impressions of Change scale (CGI-C apathy).

RESULTS

Meta-analysis of four RCTs revealed an improvement in apathy among patients receiving MET compared to placebo (MD = - 5.12, p = 0.04, three trials, 144 participants) at follow-ups of 1-3 months assessed with AES score. Despite the absence of improvement on NPI-apathy subscale at follow-ups of 1-2 months (MD = - 0.74, p = 0.37, three trials, 265 participants), significant improvement was noted at follow-ups of 6 months (MD = - 1.4, p = 0.02, one trial, 180 participants). Assessment with CGI-C apathy revealed no significant association between improvement in apathy with MET use (RR = 1.38, p = 0.05, three trials, 265 participants). No significant differences in global cognitive function (using the Mini Mental State Exam) or adverse events were noted between the two groups.

CONCLUSION

While AES score suggested an early attenuation effect of MET on apathy in different domains, the NPI-apathy subscale did not show early improvement in apathy until the 6-month follow-up. Further studies with longer follow-ups are needed to elucidate the efficacy of MET for relieving caregiver burden and improving global functional performance.

Address: Department of Neurology, Chi-Mei Medical Center, Tainan city, Taiwan.; Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan city, Taiwan.; Department of Health and Nutrition, ChiaNai University of Pharmacy and Science, Tainan City, Taiwan.; Department of Medical Imaging, Chi Mei Medical Center, Tainan city, Taiwan.; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung city, Taiwan.; Department of Internal Medicine, Chi Mei Medical Center, Tainan city, Taiwan.; Department of Education, Chi Mei Medical Center, Tainan city, Taiwan.; Department of Emergency Medicine, E-Da Hospital, Kaohsiung city, Taiwan.; College of Medicine, I-Shou University, Kaohsiung city, Taiwan.; Department of Anesthesiology, Chi Mei Medical Center, No.901, ChungHwa Road, YungKung Dist, Tainan city, 71004, Taiwan. [email protected].

DOI: 10.1007/s00213-022-06261-y

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Full Text Sources:

https://doi.org/10.1007/s00213-022-06261-y

MeSH Terms: Humans, Methylphenidate, Apathy, Alzheimer Disease, Cognition