A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease.

OBJECTIVE This study examined the effects of modafinil on apathetic symptomatology, performance of activities of daily living (ADLs), and caregiver burden in individuals with Alzheimer's disease (AD). METHOD 23 participants with a diagnosis of mild-to-moderate probable AD according to National Institute of Neurologic and Communicative Disorder and Stroke-Alzheimer's Disease and Related Disorders criteria were randomized into the experimental (modafinil 200 mg daily) or control (placebo) groups. All participants were also receiving stable doses of a cholinesterase inhibitor medication. Participants completed assessments at baseline and after 8 weeks of treatment. Outcome measures included family report measures of apathy, ADL performance, and caregiver burden, as well as direct assessment of ADL performance. The study was conducted at a private psychiatric hospital in Rhode Island from September 2005 until September 2007. RESULTS Both the experimental and control groups showed reductions in apathy on the Frontal Systems Behavior Scale between baseline and final assessments (F1,20 = 18.017, P < .001, η2 = 0.474), and there was no significant additional reduction in apathy with modafinil (F1,20 = 0.008, P = .932, η2 = 0.000). Groups did not show significant changes in caregiver report of ADL performance over time (F1,19 = 0.268, P = .611). The correlation between change in apathy and change in caregiver burden was not significant (r = 0.355, P = .053), but there was a trend toward improved levels of apathy being related to decreased levels of caregiver burden. CONCLUSIONS The addition of modafinil to the standard of care treatment (cholinesterase inhibitor medication) did not result in significant additional reductions in apathy or improvements in ADL functioning. The reduction in reported apathy observed in both groups between baseline and final assessments was likely due to placebo effect. However, reductions in perceived apathetic symptomatology were correlated with reductions in reported caregiver distress and burden. Larger studies with more statistical power are needed to confirm the absence of significant effects. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01172145.