WASHINGTON – Prompt, short-term treatment with antidepressants is associated with significantly improved physical, cognitive, and survival outcomes in stroke patients–regardless of whether they have symptoms of depression, Dr. Robert Robinson said at the annual meeting of the American Academy of Clinical Psychiatrists.
“Perhaps all patients who suffer a stroke should be evaluated by a psychiatrist and treated with antidepressants, because [these drugs] appear to improve their recovery,” said Dr. Robinson, who serves on the speakers' bureau for Forest Laboratories Inc. He also serves as a consultant for Hamilton Pharmaceuticals Inc. and Avanir Pharmaceuticals.
Data from recent studies have shown that antidepressants have beneficial effects on physical and cognitive recovery (as well as on mortality) after a stroke and that these effects may last for several years, said Dr. Robinson, professor and head of the department of psychiatry at the University of Iowa, Iowa City.
Dr. Robinson shared data that he collected in collaboration with his colleague at the university, Dr. Kenji Narushima, on 34 stroke patients who were treated with nortriptyline, fluoxetine, or a placebo starting within a month of having a stroke (average of 19 days after the stroke) and 28 patients who began treatment more than a month after the stroke (J. Nerv. Ment. Dis. 2003;191:645–52).
The nortriptyline doses were 25 mg/day for the first week, which then was increased to 50 mg/day for weeks 2–3, 75 mg/day for weeks 4–6, and 100 mg/day for the final 6 weeks.
The fluoxetine dosage started at 10 mg/day for the first 3 weeks, which then was increased to 20 mg/day for weeks 4–6, 30 mg/day for weeks 7–9, and 40 mg/day for the final 3 weeks, the investigators reported.
The patients who were treated early had a significantly better recovery in activities of daily living than did those who were treated later, even after a logistic regression analysis controlled for several factors, including existing depression, motor impairment, and psychiatric history. The finding suggests that patients who are given antidepressants–whether they are depressed or not–within the first month after a stroke recover better than if they are given antidepressants at a later date, Dr. Robinson said.
Similarly, a study of cognitive outcomes based on executive function tests showed that patients who were treated with antidepressants within a month of a stroke scored significantly higher at 21 months' follow-up, compared with patients who received a placebo.
The improvements were independent of any diagnosis of depression at the start of treatment.
Not all patients respond to antidepressant medication, but those who do seem to gain a cognitive effect that lasts, Dr. Robinson said.
Stroke patients who receive antidepressants also tend to live longer.
Dr. Robinson cited results from a randomized study of 104 stroke patients on which he was a coinvestigator. The patients received 12 weeks of either nortriptyline or a placebo, and 68% of the nortriptyline patients were alive after 9 years, compared with 36% of placebo patients.
Interestingly, the placebo patients were significantly more likely to have died of cardiovascular events, while the patients who took antidepressants were more likely to have died from other causes (Am. J. Psychiatry 2003;160:1823–9).
The long-term benefits from only 12 weeks of antidepressant therapy are remarkable, Dr. Robinson said, although the mechanism of action that drives the benefits remains uncertain.
One possible explanation for the long-term effect is that the antidepressants foster nerve growth, and the growth of new nerves may protect against a future stroke. “But where the neurogenesis is occurring is something that is a particularly intriguing question,” Dr. Robinson said. Neurogenesis may be involved in a neurophysiologic mechanism that turns on or off for extended periods of time in response to antidepressants, but more research is needed, he said.
“A major goal of clinical psychiatry is to see how our treatments affect outcome,” he added.
Antidepressants foster nerve growth, and growth of new nerves may protect against a future stroke. DR. ROBINSON
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