Clinical Question: Will treatment with an antidepressant reduce poststroke mortality?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: Depression is common in patients who have had an acute stroke. Currently, it is uncertain whether use of antidepressant therapy in these patients reduces poststroke mortality. Patients 25 to 89 years of age who had an acute stroke in the previous six months were assigned randomly (uncertain allocation concealment) to receive 12 weeks of fluoxetine, nortriptyline, or placebo. Fluoxetine is contraindicated in patients with an intracerebral hemorrhage and nortriptyline is contraindicated in patients with cardiac conduction abnormalities, so patients with these conditions were not given the contraindicated medications. Dosages of medications in the study were those commonly used in clinical practice. Depression was defined according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., and the Hamilton Depression Rating Scale.

Of the 104 patients enrolled in the study, 23 (22 percent) dropped out before completing the 12-week treatment protocol. However, mortality data were obtained for all patients at nine years of follow-up. The overall dropout rate (33 percent) was statistically higher in the patients receiving fluoxetine. Persons assessing outcomes were blinded to treatment group assignment. After nine years, 50 (48.1 percent) of the 104 patients had died. Interestingly, no significant association was noted between depression at baseline and long-term mortality: 50 percent of the patients who died were given a diagnosis of depression at baseline compared with 57.4 percent of those who survived. Using intention-to-treat analysis, 59.2 percent of the patients assigned to antidepressant therapy survived compared with 36.4 percent of the patients who received placebo (P =.03; number needed to treat = four). There was no difference in survival rates between patients assigned to fluoxetine and those assigned to nortriptyline. Patients in all of the groups were treated similarly with standard post-stroke medical management. A logistic regression model showed that the reduction in the mortality rate with antidepressant therapy remained significant after controlling for other comorbid conditions.

Bottom Line: Treatment with fluoxetine or nortriptyline for 12 weeks during the first six months after a stroke reduces the mortality rate in depressed and nondepressed patients. Although this trial is relatively small, the results suggest that we should strongly consider antidepressant treatment following stroke in patients who show any symptoms of depression or who are at significant risk of developing depression (e.g., those with family or personal history of depression). (Level of Evidence: 1b–)