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

• What is the primary question addressed by this study? Do clinical characteristics of participants in the ADMET 2 trial predict better response to methylphenidate for the treatment of apathy in Alzheimer's disease? • What is the main finding of this study? Participants without anxiety or agitation, who were younger, taking a cholinesterase inhibitor, with 73–80 mm Hg diastolic blood pressure, having low functional capacity, were found to respond better to methylphenidate. Combining these characteristics in a multivariate model provided individualized prediction of treatment response. • What is the meaning of the finding? These clinical characteristics may affect the efficacy of methylphenidate in treating apathy, and may help clinicians identify patients most likely to respond to treatment. 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. Univariate and multivariate analyses of 22 clinical predictors of response chosen a priori. Data from the ADMET 2 randomized, placebo controlled multi-center clinical trial. Alzheimer's disease patients with clinically significant apathy. Apathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A). In total, 177 participants (67% male, mean [SD] age 76.4 [7.9], mini-mental 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. Individuals who were not anxious or agitated, younger, prescribed a ChEI, with optimal (73–80 mm Hg) diastolic blood pressure, or having 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. [ABSTRACT FROM AUTHOR]