Does fluoxetine reduce apathetic and depressive symptoms after stroke? An analysis of the EFFECTS trial dataset.

OBJECTIVE: Apathy is a common and disabling symptom after stroke with no proven treatments. Selective serotonin reuptake inhibitors are widely used to treat depressive symptoms post stroke but whether they reduce apathetic symptoms is unknown. We determined the effect of fluoxetine on post stroke apathy in a post-hoc analysis of the EFFECTS (Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke) trial. METHODS: EFFECTS enrolled patients >=18 years between 2-15 days after stroke onset. Participants were randomly assigned to receive oral fluoxetine 20 mg once daily or matching placebo for 6 months. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and 6 months. Individual items on this scale were divided into those reflecting symptoms of apathy and depression. Symptoms were compared between fluoxetine and placebo groups. RESULTS: Of 1500 participants enrolled, complete MADRS data was available for 1369. The modified intention-to-treat population included 681 patients in the fluoxetine group and 688 in the placebo group. Confirmatory factor analysis revealed that apathic, depressive, and anhedonic symptoms were dissociable. Apathy scores increased in both fluoxetine and placebo groups (both P≤0.00001). In contrast fluoxetine was associated with a reduction in depressive scores, (P=0.002)Conclusions. Post-stroke apathetic and depressive symptoms respond differently to fluoxetine treatment. Our analysis suggests fluoxetine is ineffective in preventing post-stroke apathy.