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

Psychopharmacology volume 239, pages 3743–3753 (2022)Cite this article

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.

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Author notes

  1. Cheuk-Kwan Sun and Kuo-Chuan Hung contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Chi-Mei Medical Center, Tainan city, Taiwan

    Chia-Wei Lee

  2. Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan city, Taiwan

    Jui-Yi Chen

  3. Department of Health and Nutrition, ChiaNai University of Pharmacy and Science, Tainan City, Taiwan

    Jui-Yi Chen & Ching-Chung Ko

  4. Department of Medical Imaging, Chi Mei Medical Center, Tainan city, Taiwan

    Ching-Chung Ko

  5. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung city, Taiwan

    Ching-Chung Ko

  6. Department of Internal Medicine, Chi Mei Medical Center, Tainan city, Taiwan

    Min-Hsiang Chuang

  7. Department of Education, Chi Mei Medical Center, Tainan city, Taiwan

    Wen-Wen Tsai

  8. Department of Emergency Medicine, E-Da Hospital, Kaohsiung city, Taiwan

    Cheuk-Kwan Sun

  9. College of Medicine, I-Shou University, Kaohsiung city, Taiwan

    Cheuk-Kwan Sun

  10. Department of Anesthesiology, Chi Mei Medical Center, No.901, ChungHwa Road, YungKung Dist, Tainan city, 71004, Taiwan

    Kuo-Chuan Hung

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  1. Chia-Wei Lee
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Contributions

Cheuk-Kwan Sun and Kuo-Chuan Hung contributed equally to this work. Chia-Wei Lee and Jui-Yi Chen: Conceptualization, Methodology, Software; Ching-Chung Ko and Wen-Wen Tsai: Data curation; Kuo-Chuan Hung and Chia-Wei Lee: Writing- Original draft preparation; Cheuk-Kwan Sun and Kuo-Chuan Hung: Visualization, Investigation; Cheuk-Kwan Sun: Supervision; Kuo-Chuan Hung and Cheuk-Kwan Sun: Software, Validation; Kuo-Chuan Hung and Cheuk-Kwan Sun: Writing—Reviewing and Editing.

Corresponding author

Correspondence to Kuo-Chuan Hung.

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Lee, CW., Chen, JY., Ko, CC. et al. Efficacy of methylphenidate for the treatment of apathy in patients with Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled studies. Psychopharmacology 239, 3743–3753 (2022). https://doi.org/10.1007/s00213-022-06261-y

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Keywords

  • Methylphenidate
  • Apathy Evaluation Scale
  • Alzheimer’s disease
  • Neuropsychiatric inventory apathy