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Study of Antidepressants Finds Little Disparity in Suicide Risk

Amid an international debate about the side effects of drugs taken for depression, a large-scale analysis of British medical records has found little difference in rates of suicidal behavior among patients given some of the most commonly prescribed medications. The risk is highest when patients begin taking the drugs, as doctors have long suspected, and tapers off quickly after that.

The study, which is being reported today in the Journal of the American Medical Association, found no evidence that withdrawal from the drugs put patients at an increased risk of suicide.

The analysis, conducted and financed by the Boston University School of Medicine, is the largest to compare the suicide risk of the antidepressant drugs Paxil and Prozac with that of older medications like amitriptyline. All the drugs have been commonly prescribed for people with severe depression.

Patients were three to four times more likely to report thoughts of suicide or attempts at it in the first month of treatment than they were after three months on the drugs, the analysis found. The findings were similar for each medication, whether prescribed for adults or children.

Experts said the study should reassure psychiatrists and other doctors concerned about hidden differences between the risks of the newer antidepressants, like Prozac, and the older varieties. The experts also said that it confirmed the importance of watching patients closely when they begin treatment.

"It's starting treatment itself, more than what drug you start with, that's the important factor," said Dr. James A. Kaye, an author of the study along with Dr. Hershel Jick and Dr. Susan S. Jick. Most psychiatrists believe that the drugs reduce the overall risk of suicide.

The analysis does not help answer the central question underlying the safety debate: Do some people become more suicidal on the drugs? Compared with those on placebos, depressed children in particular have reported an increase in suicidal thoughts when taking antidepressants during some clinical trials.

"This study does not speak at all to taking the drugs versus not taking them," said Dr. Jeffrey A. Lieberman, a professor of psychiatry and pharmacology at the University of North Carolina.

Concerns that the drugs might increase the suicide risk for some children prompted the Food and Drug Administration to caution doctors earlier this year that young patients should be monitored carefully, especially during the first weeks of treatment. Late last year, British health officials banned the use of all drugs but Prozac for treating depression in patients younger than 18.

The Boston University doctors analyzed the computerized medical records of 159,810 patients treated for depression between 1993 and 1999 in Britain, which keeps a detailed database of health information on millions of its citizens. The patients ranged from 10 to 69 years old and could have taken only one brand of antidepressant: Prozac, from Eli Lilly; Paxil from GlaxoSmithKline; amitriptyline; or dothiepin, which is not available in the United States.

Among these patients, the researchers found 555 had showed signs of suicidal thinking or behavior for the first time in the months after they started on antidepressants.

Regardless of age or sex, they were four times more likely to begin acting suicidal in the first 10 days of treatment than they were after 90 days. And they were three times more likely to show such signs during the rest of the first month of treatment than later on.

It did not matter much which drug they took. The risk of suicidal behavior for those who started on Paxil was slightly higher than for those on the other drugs, but the difference was so small that it could have been due to chance or to something the researchers did not take into account, they said. For instance, Dr. Kaye said, Paxil, the newest of the drugs, may have been prescribed for suicidal cases more often than the others.

Researchers do not know why the risk of suicidal behavior was highest during the first weeks of treatment. The most likely explanation, they said, is that patients are at a low point when depression is diagnosed and they start on a drug. 

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