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Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: A randomized, placebo-controlled trial


Rosenberg, Paul B., Lanctôt, Krista L., Drye, Lea T., Herrmann, Nathan, Scherer, Roberta W., Bachman, David L., Mintzer, Jacobo E.


Journal of Clinical Psychiatry, Volume: 74, No.: 8, Pages.: 810-816

Year of Publication



Objective: In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer’s disease. We further assessed this finding in the Apathy in Dementia Methylphenidate Trial (ADMET). Method: Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer’s disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. Results: 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks’ treatment, mean (SD) change in AES score was -1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group. Conclusions: Methylphenidate treatment of apathy in Alzheimer’s disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer’s disease. Trial Registration: identifier: NCT01117181. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

Bibtex Citation

@article{Rosenberg_2013, doi = {10.4088/jcp.12m08099}, url = {}, year = 2013, month = {apr}, publisher = {Physicians Postgraduate Press, Inc}, volume = {74}, number = {08}, pages = {810--816}, author = {Paul B. Rosenberg and Krista L. Lanct{^{o}}t and Lea T. Drye and Nathan Herrmann and Roberta W. Scherer and David L. Bachman and Jacobo E. Mintzer}, title = {Safety and Efficacy of Methylphenidate for Apathy in Alzheimer's Disease}, journal = {J. Clin. Psychiatry} }


aka, alzheimer’s disease, apathy, cognition, drug therapy, methylphenidate, ritalin

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

Behaviour, Cognition, Depression and Anxiety

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions