Methylphenidate effective treatment of apathy in Alzheimer's Disease, finds JAMA study

USA: A recent study in the JAMA Neurology journal has found methylphenidate to be a safe and effective medication for the treatment of apathy in Alzheimer's disease (AD) patients. This may reduce symptoms and caregiver burden.

Apathy is a condition characterized by diminished will or initiative and is one of the most common neuropsychiatric symptoms in AD patients. Its presence is associated with excess disability, significant caregiver burden, mortality, and increased medical costs. Currently, no treatments are proven to be effective for treating apathy in Alzheimer's Disease (AD), but catecholaminergic agents such as methylphenidate hold promise. 

Jacobo Mintzer, Ralph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, and colleagues, therefore, aimed to measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer's disease.

The study was designed as a multicenter randomized placebo-controlled clinical trial. It was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included.

Out of 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male.

The results of the study were found to be

• A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, −1.25).

• The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16).

• At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was found to be 1.90.

• The difference in mean change from baseline to 6 months was estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups.

Dr. Mintzer and the team concluded that "This study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer's disease."

Reference:

Mintzer J, Lanctôt KL, Scherer RW, et al. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol. Published online September 27, 2021. doi:10.1001/jamaneurol.2021.3356