Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial

Objective: The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed heterogeneity in response. We assessed clinical predictors of response to help determine individual likelihood of treatment benefit from methylphenidate. Design: Univariate and multivariate analyses of 22 clinical predictors of response chosen a priori. Setting: Data from the ADMET 2 randomized, placebo controlled multi-center clinical trial. Participants: Alzheimer's disease patients with clinically significant apathy. Measurements: Apathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A). Results: In total, 177 participants (67% male, mean [SD] age 76.4 [7.9], minimental state examination 19.3 [4.8]) had 6-months follow up data. Six potential predictors met criteria for inclusion in multivariate modeling. Methylphenidate was more efficacious in participants without NPI anxiety (change in NPI-A -2.21, standard error [SE]:0.60) or agitation (-2.63, SE:0.68), prescribed cholinesterase inhibitors (ChEI) (-2.44, SE:0.62), between 52 and 72 years of age (-2.93, SE:1.05), had 73-80 mm Hg diastolic blood pressure (-2.43, SE: 1.03), and more functional impairment (-2.56, SE:1.16) as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living scale. Conclusion: Individuals who were not anxious or agitated, younger, pre-scribed a ChEI, with optimal (73-80 mm Hg) diastolic blood pressure, or hav-ing more impaired function were more likely to benefit from methylphenidate compared to placebo. Clinicians may preferentially consider methylphenidate for apathetic AD participants already prescribed a ChEI and without baseline anxiety or agitation.

Automated summary

The study found that younger patients, those prescribed cholinesterase inhibitors, with optimal diastolic blood pressure, and without anxiety or agitation were more likely to benefit from treatment with methylphenidate for apathy in Alzheimer's disease.