Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

Abstract

Objective In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Alzheimer's Disease 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.

ADHD in old age: a review of the literature and proposal for assessment and treatment

“…This study supported the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. Two out of the 60 patients experienced serious adverse events consisting of delusions, agitation, anger, irritability, and insomnia [93].…”

Depression and Cognition in the Elderly

“…Stimulants are another understudied area. Methylphenidate has also been used off-label for depression, and it may have benefits for apathy in AD in the absence of depressive features (Rosenberg et al 2013); however, stimulants have not been shown to improve cognition in randomized controlled trials of MCI or AD. Additional studies will need to examine whether methylphenidate may have positive effects for older depressed adults with comorbid cognitive impairment.…”

Psychiatric and Medical Comorbidity in the Primary Care Geriatric Patient—An Update

“…Notably, another study found that implementing a systematic approach to pain management in nursing homes led to significantly reduced agitation [84]. With respect to the treatment of apathy, two small studies suggest benefits from methylphenidate though accompanied by the expected adverse effects such as elevated blood pressure [85,86].…”