Nefiracetam is a novel pyrrolidone-type nootropic compound shown in preliminary trials to increase blood flow and improve patient outlook and energy following stroke. Of 137 stroke patients with major depression, 70 also met published diagnostic criteria for apathy (51.1%) and were randomly assigned either to placebo or 600 mg or 900 mg of nefiracetam per day, and received at least 4 weeks of treatment. Using the group with at least 4 weeks of treatment as the intention-to-treat sample with last observation carried forward, repeated measures analysis of variance of Apathy Scale scores demonstrated a significant time-by-treatment interaction. Patients taking 900 mg nefiracetam had a significantly greater change in Apathy Scale scores compared to 600 mg of nefiracetam or placebo. Future studies should assess whether apathy without depression may respond to this novel treatment.