Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: A placebo-controlled, double-blind study

Objective: This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive im pairments after stroke. Method: A total of 104 patients with acute stroke e nrolled between 1991 and 1997 entered a double-blind randomized study compa ring nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were gi ven over 12 weeks. Response to treatment of depression for individual patie nts was defined as a greater-than-50% reduction in scores on the Hamilton R ating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was def ined as a significantly higher mean score from baseline to end of the treat ment trial, compared with patients treated with placebo, on measures of imp airment in activities of daily living and levels of cognitive and social fu nctioning. Results: Nortriptyline produced a significantly higher response rare than fluoxetine or placebo in treating poststroke depression, in impro ving anxiety symptoms, and in improving recovery of activities of daily liv ing as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social function ing among depressed or nondepressed patients. Fluoxetine in increasing dose s of 10-40 mg/day led to an average weight loss of 15.1 pounds (8% of initi al body weight) over 12 weeks of treatment that was not seen with nortripty line or placebo. Conclusions: Given the doses of medication used in this st udy, nortriptyline was superior to fluoxetine in the treatment of poststrok e depression. Demonstrating a benefit of antidepressant treatment in recove ry from stroke may require the identification of specific subgroups of pati ents, alternative measurement scales, or the optimal time of treatment.