Effect of antidepressants on the course of disability following stroke

Abstract

Objective: Stroke often produces marked physical and cognitive impairments leading to functional dependence, caregiver burden, and poor quality of life. We examined the course of disability during a 1-year follow-up period after stroke among patients who were administered antidepressants for 3 months compared to patients given placebo for 3 months.

Methods: A total of 83 patients entered a double-blind randomized study of the efficacy of antidepressants to treat depressive disorders and reduce disability after stroke. Patients were assigned to either fluoxetine (N = 32), nortriptyline (N = 22) or placebo (N = 29). Psychiatric assessment included administration of the Present State Examination modified to identify DSM-IV symptoms of depression. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale. The modified Rankin Scale was used to evaluate the disability of patients at initial evaluation and at quarterly follow-up visits for 1 year. Impairment in activities of daily living was assessed by Functional Independence Measure at the same time.

Results: During the 1-year follow-up period, and after adjusting for critical confounders including age, intensity of rehabilitation therapy, baseline stroke severity, and baseline Hamilton Depression Rating Scale, patients who received fluoxetine or nortriptyline had significantly greater improvement in modified Rankin Scale scores compared to patients who received placebo (t [156] = -3.17, p = 0.002).

Conclusions: Patients treated with antidepressants had better recovery from disability by 1-year post stroke (i.e., 9 months after antidepressants were stopped) than patients who did not receive antidepressant therapy. This effect was independent of depression suggesting that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke.

FIGURE 1

A Schematic Display of the Flow of Patients included in This Study

FIGURE 2

Change in modified Rankin scores over 1 year following a recent stroke. Patients with or without initial depression were treated double blind from baseline to 3 months with fluoxetine (10–40 mg/d) or nortriptyline (25–100 mg/d), or placebo. Patients were followed at 6, 9 and, 12 months after treatment. Mixed model analysis showed a significantly better recovery in the patients given either fluoxetine (t [119] = 2.14, p = 0.035) or nortriptyline (t [105] = 2.91, p = 0.004), compared with placebo treatment. Note that the recovery in patients given fluoxetine or nortriptyline continued throughout the 12 months, although treatment was stopped at 3 months.