title: Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial.
abstract: 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).
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01117181.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.forename: Roberta W
authors.initials: RW
authors.lastname: Scherer
authors.forename: David L
authors.initials: DL
authors.lastname: Bachman
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.lastname: ADMET Investigators
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D057565:Apathy / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D000077408:Modafinil; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011594:Psychometrics
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000077408:Modafinil
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