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Older Tricyclics More Effective Than Newer Antidepressants In Post-Stroke Depression

IOWA CITY, IA -- March 2, 2000 -- Newer is generally thought of as better. However, that may not be the case for antidepressive medication to treat post-stroke depression. The disorder affects nearly 40 percent of the 400,000 individuals in the United States who annually survive strokes.

University of Iowa Health Care researchers found that for treating depression in individuals who had a stroke and did not have heart conditions, the tricyclic antidepressant nortriptyline (Aventyl or Pamelor) is more effective than fluoxetine (Prozac), part of a newer class of medication called selective serotonin re-uptake inhibitors (SSRIs). This was the first study to compare the two major classes of antidepressants in post-stroke patients. The findings appeared in today's issue of the American Journal of Psychiatry.

"We were surprised to find that nortriptyline was more effective in treating patients with post-stroke depression than was fluoxetine, which was no better than the placebo," said Robert G. Robinson, M.D., UI professor and head of psychiatry and the study's lead investigator. "After nortriptyline treatment, patients showed less depression and anxiety, and they were better able to perform daily tasks such as dressing and feeding themselves."

He added that physicians may be overlooking nortriptyline and prescribing fluoxetine to post-stroke patients because the latter has few side effects at lower dosages, can be used in people with heart disease and is generally a popularly used drug.

Post-stroke depression is a relatively common disorder that can occur during the first two years after a stroke. Approximately 20 percent of stroke survivors will develop major depression, while another 20 percent will have a less severe form of the disorder. Left untreated, major depression can last from nine to 12 months or, in a minority of patients, two or more years.

Robinson and other UI investigators reported in 1984 that nortriptyline, the tricyclic antidepressant, was quite effective in treating post-stroke depression in patients without certain types of heart disease. However, selective serotonin re-uptake inhibitors (SSRIs) such as Prozac were later developed and increasingly used for treating depression.

"Because of the great popularity of SSRIs, we wanted to determine whether there were better ways of treating stroke than what we had found with nortriptyline in 1984," Robinson said.

Over six years, the investigators compared nortriptyline, fluoxetine and a placebo in 104 patients within six months of their strokes. The participants included a group of primarily white, urban and rural patients who had major or minor depression and a control group of demographically similar stroke survivors who were not depressed.

Of the participants who completed the 12-week treatment cycle and had some form of depression, improvement appeared in 77 percent of those treated with the tricyclic nortriptyline, 14 percent who received the SSRI fluoxetine and 31 percent who received the inactive substance.

Robinson said some studies at other institutions have also suggested that patients with depression associated with difficult physical illness such as a post-stroke condition do not respond as well to SSRIs as patients who are younger or in better overall health.

In the UI study, daily dosages of fluoxetine were gradually increased from 10 mg to 40 mg. The dosages above 10 mg caused side effects of nausea, vomiting and severe diarrhea.

"We felt we needed to look at the spectrum of dosages that are used in practice to treat depression after stroke," Robinson said. Physicians typically prescribe a 20 mg daily dosage of the SSRI, but dosages of 40 mg are also prescribed.

However, none of the SSRI dosages had the effect nortriptyline did of reducing depression and enhancing activities of daily living. The nortriptyline dosages started at 25 mg and were gradually increased to 100 mg.

Robinson said it is possible that even newer SSRIs, such as citalopram, may be effective. However, the improvement of depression scores was greater in the UI treatment using nortriptyline than in a recent study in Denmark using citalopram, and further research is needed to determine the appropriate dosages of the newer SSRI.

He added, "No one knows exactly how any of the antidepressants work to cure depression, but we do know they enhance the availability of certain neurotransmitters in the brain."

SSRIs specifically increase the availability of serotonin to promote recovery. Tricyclics such as nortriptyline not only affect serotonin but also increase the availability of other neurotransmitters such as dopamine and norepinephrine.

Most of the patients in the UI study were from the Younker Rehabilitation Center of the Iowa Methodist Medical Center in Des Moines. The other participants were treated at the University of Iowa, the Veterans Affairs Medical Center in Iowa City or the FLENI Institute in Buenos Aires.

The study was supported in part by grants from the National Institute of Mental Health, FLENI and Fundacion Perez Companc. The Eli Lilly Pharmaceutical Co. supplied the fluoxetine and its placebo. The UI pharmacy supplied the nortriptyline and its placebo.

Related Links: fluoxetine (Prozac) and Eli Lilly Pharmaceutical Co.

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