A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.

BACKGROUND: To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy.

METHODS: A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS).

RESULTS: Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14).

CONCLUSIONS: Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.