Fluoxetine for Stroke: A Mixed Bag of Outcomes

Stroke is the leading neurologic cause of burden operationalized in terms of disability-adjusted life-years. After stroke, motor deficits, cognitive deficits, and depression cause loss of independence, disability, decreased functioning, and reduced quality of life; these persist into the long term. There are theoretical grounds to consider that, through neuroplasticity and other mechanisms, such impairments can be prevented or attenuated by the early introduction of a selective serotonin reuptake inhibitor such as fluoxetine. However, a recent meta-analysis of 13 randomized controlled trials (RCTs; pooled N = 4,145) found that fluoxetine neither improved independence nor reduced disability; whereas fluoxetine did reduce the risk of poststroke depression, it did not improve other outcomes, such as motor and cognitive outcomes, but, rather, was associated with many adverse outcomes. Two very large RCTs were subsequently published. The findings of these RCTs, in combination with the findings of the meta-analysis, suggest that, if fluoxetine is started within 2 weeks of ischemic or hemorrhagic stroke and is administered in a dose of 20 mg/d for 3-6 months, there is a 3%-4% reduced risk of new onset depression; however, there is no improvement in the likelihood of achieving independence or of reduction of disability. The risk of several adverse outcomes is increased; these include falls (by 2%), bone fractures (by 1%-2%), seizures (by 1%), and hyponatremia (by 1%). Fluoxetine is also associated with the theoretical risk of adverse drug interactions in stroke patients. In summary, there does not appear to be a role for the routine use of fluoxetine in poststroke pharmacologic care.