Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)
Lijuan Zeng1, Jamie Perin2, Alden L Gross1
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Objectives:
To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia.
Methods:
The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist.
Results:
The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period.
Conclusions:
MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.
Insights
Methylphenidate (MPH) for Alzheimer's Disease (AD) apathy showed modest weight loss and increased falls but was otherwise safe. Clinicians should monitor patient weight during MPH treatment for apathy in AD.
Area of Science:
- Gerontology
- Neuroscience
- Clinical Pharmacology
Background:
- Apathy is a common and disabling symptom in Alzheimer's Disease (AD).
- Methylphenidate (MPH) is a stimulant medication that has been investigated for treating apathy in various conditions.
- The safety profile of MPH in elderly patients with AD and comorbidities requires careful evaluation.
Purpose of the Study:
- To assess clinically significant adverse events (AEs) associated with methylphenidate (MPH) treatment compared to placebo in patients with Alzheimer's Disease (AD) experiencing apathy.
- Specifically examine AEs including weight loss, vital signs, falls, and insomnia.
Main Methods:
- A multicenter, randomized, placebo-controlled trial (ADMET2) involving participants with apathy and AD.
- Monthly measurements of vital signs and weight over a 6-month follow-up period.
- Systematic reporting of adverse events, including insomnia and falls, via symptom checklists.
Main Results:
- The methylphenidate (MPH) group experienced statistically significant, modest average weight loss (2.8 lb) compared to placebo over 6 months.
- No significant differences in blood pressure were observed between the MPH and placebo groups.
- A higher incidence of falls was reported in the MPH group (10 participants) versus the placebo group (6 participants), with no significant difference in insomnia.
Conclusions:
- Methylphenidate (MPH) appears relatively safe for treating apathy in Alzheimer's Disease (AD) patients, even with common comorbidities.
- Clinicians should monitor for modest weight loss during MPH treatment for apathy in AD.
- While falls were more frequent in the MPH group, severe cardiovascular events were not reported, suggesting a manageable safety profile.
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