Fluoxetine Opens Window to Improve Motor Recovery After Stroke

FLOW Trial is a randomized, placebo-controlled, blinded phase II trial evaluating the efficacy of coupling antidepressant therapy (e.g., selective serotonin reuptake inhibitor - fluoxetine) with exercise rehabilitation across multiple Canadian sites in 176 stroke patients. 88 patients will be enrolled in each arm of the study. Both groups will receive an exercise program in addition to standard of care rehabilitation, but only one group (the intervention group) will receive the active drug fluoxetine.

Study participants will be evaluated at baseline, post-exercise program and 6-months post-exercise program. While enrolled in the study, participants will be required to take part in a 12 week, 3 times per week exercise program. Evaluators and patients will be blind to the treatment administered. The trial is constructed with randomization to remove selection and allocation biases and to ensure greater validity in observed differences in the outcome measures. The Applied Health Research Centre (AHRC) in Toronto will act as the coordinating and analysis center.

Inclusion criteria

• 25 years of age or older
• Days post stroke must be between 2 to 12 months when enrolled (i.e. day of consent)
• Patient-reported hemiparesis of the lower extremity

Exclusion criteria

• Patients with subarachnoid hemorrhage
• Pre-morbid modified Rankin score > 2
• Substantial premorbid disability or pre-existing deficit or language comprehension deficit that could interfere with assessments
• Diagnosis of major depressive disorder/anxiety disorder requiring antidepressant use within 6 weeks of enrolment
• Taking neuroleptic drugs, benzodiazepines, monoamine oxidase inhibitors within 30 days of enrolment
• Unstable serious medical condition (e.g., terminal cancer, renal or liver failure, congestive heart failure)
• Resting blood pressure exceeding 180/100mmHg
• Requires more than a one person assist for transfer
• Planned surgery that would affect participation in the trial
• Participating in another formal lower limbs exercise program more than one day per week
• History of QT prolongation or concomitant use of clearly identified potential QT prolonging drugs, at the investigators discretion (e.g. amiodarone, bepridil, dysopyramide, dofetilide, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol, phenothiazines, pimozide, ziprasidone, TCAs, halofantrine, cisapride, and probucol)
• History of glaucoma
• Patients with a history of thrombocytopenia or clinically significant bleeding disorder or use of NSAID, ASA or other anticoagulants, at the investigators' discretion
• History of convulsive disorders
• Potential pregnancy (per screening algorithm)
• Patients with an ongoing history of illicit drug use and/or alcohol abuse
• Patient unwilling or unable to comply with trial requirements
• Patient unable to understand English or communicate with the study team with staff support or translation services