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Effect of Antidepressants on the Course of Disability Following Stroke

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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.

Section snippets

Patient Selection

A total of 343 patients between 18 and 85 years, who had a stroke in the previous 6 months, were screened for participation in a study of antidepressant therapy. The protocols were approved by the institutional review boards and written informed consent was obtained from each subject. In addition, we required that the subject's immediate family and treating physician also agreed to the subject's participation. Exclusion criteria included: (1) any other significant medical illness that would

Participants

We compared the background characteristics of the patient treated with fluoxetine (N = 32) and those treated with nortriptyline (N = 22) and found no significant differences except there were significantly fewer women in the fluoxetine compared to the nortriptyline group (Fisher's exact test, p = 0.04). Furthermore, mixed model analysis was performed on the mRS of the nortriptyline and fluoxetine groups controlling for age, total hours of physical rehabilitation, baseline NIHSS score, and

DISCUSSION

This study found that the administration of either nortriptyline and fluoxetine for 3 months significantly reduced disability from stroke over 1 year compared with placebo, even after controlling for age, total hours of physical rehabilitation, baseline severity of stroke (using the NIHSS), and baseline HDRS score. To our knowledge, this is the first time that, independent of depression, antidepressant medication has been shown using double blind methodology to be associated with physical

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    The authors would like to thank Stephanie Rosazza, B.A., study coordinator, and Teresa Kopel, M.A., The University of Iowa.

    This work is supported in part by NIH grants R01-MH 40355 and R01-MH65134. Dr. Adams received research support from NIH-NINDS (Consultant R01NS19632, and coinvestigator, 5U01NS041895, both 2001–2009), Mayo Foundation for Medical Education/Research (Coinvestigator, 2000–2009), Boehringer–Ingelheim Pharm (Coinvestigator 2003–2009), Merck, Scherling-Plough, and MNT Medical (2003–2009). Dr. Robinson is a consultant for Avanir Pharmaceutical. Dr. Mikami was supported by a grant from Tokai University, Kanagawa, Japan. Drs. Jorge, Davis, Leira and Ms. Jang have no disclosures to report.

    *

    These authors contributed equally to the manuscript.

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