

Bruce Bower
In the past 2 years, public and government concerns about a widely used class of antidepressant drugs have grown. There have been indications that these selective serotonin reuptake inhibitors, or SSRIs, may cause people to try to kill themselves. In March, the Food and Drug Administration instructed the makers of 10 such medications to include in their labeling a recommendation for close physician monitoring for suicidal tendencies.
Into this charged atmosphere comes an unprecedented attempt to evaluate suicides in a large population of depressed individuals taking antidepressant drugs for months or years. The study analyzed data collected on more than 2,500 patients prescribed any of four antidepressants: two SSRIs and two older drugs.
Both attempted and completed suicides displayed a notable jump in the month after patients started antidepressant treatment, report physician Hershel Jick of Boston University School of Medicine and his colleagues. These risks were similar among people treated with an SSRI—either fluoxetine (Prozac) or paroxetine (Paxil)—or a tricyclic antidepressant—either amitriptyline or dothiepin.
Antidepressant treatment usually takes several weeks to kick in, so the suicide surge after receiving a prescription probably reflects the insidious influence of the continuing depression, Jick's group contends. However, it's also possible that all four drugs initially cause depression to worsen rapidly, leading to suicide.
"If these drugs … make people more depressed, each of them is doing it to the same extent, not just the SSRIs," remarks study coauthor James A. Kaye, a Boston University epidemiologist.
The new results appear in the July 21 Journal of the American Medical Association.
Jick's team consulted a database on medical patients treated in the United Kingdom between 1993 and 1999. That source yielded 555 depressed people, ages 10 to 69, who had begun antidepressant treatment and then ruminated about or unsuccessfully attempted suicide within 90 days. No suicide-related problems emerged for another 2,062 depressed people in the same age range who started taking an antidepressant. Rises in suicide attempts after starting antidepressant treatment were similar in teenagers and adults and in men and women.
Completed suicides increased most sharply within 9 days of beginning antidepressant treatment. Of the 17 patients who killed themselves within 3 months of taking one of the drugs, all were at least 20 years old.
Although the new report offers little to suggest that SSRIs uniquely foster suicide, it's unlikely to ease a "general crisis of confidence" in how antidepressant use is regulated, especially for children, remark psychiatrist Simon Wessely and psychologist Robert Kerwin, both of the Institute of Psychiatry in London, in an editorial published with Jick's article.
Clinical trials that uncover no beneficial or adverse effects of SSRIs on depressed adults and children often go unpublished, says psychiatrist Paul Ramchandani of the University of Oxford in England. Only in late June did one pharmaceutical company, GlaxoSmithKline, agree to publish all its data on paroxetine and post the findings online (http://www.gsk.com/).
In company-funded trials that included more than 1,100 children and teens treated with paroxetine for depression or an anxiety disorder, no one committed suicide. Suicidal behavior occurred in 2.4 percent of youngsters during paroxetine treatment, compared with 1.1 percent of those given placebo pills. This difference wasn't statistically significant.
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I have been puzzled at the consternation over the findings in this article. It's common knowledge among people who treat patients with major depression that the time of greatest risk for suicide is when depression begins to lift. The person finally has more energy and mental focus but may still feel awful. Resolved never to feel so bad again, they use their increasing energy to plan and carry out suicides. Hence, one would predict that an effective antidepressant might well lead to increased suicide attempts early in treatment.
Joel Denney
Oakland, CA
Jick, H., J.A. Kaye, and S.S. Jick. 2004. Antidepressants and the risk of suicidal behaviors. Journal of the American Medical Association 292(July 21):338–343. Abstract available at http://dx.doi.org/10.1001/jama.292.3.338.
Wessely, S., and R. Kerwin. 2004. Suicide risk and the SSRIs. Journal of the American Medical Association 292(July 21):379–381. Extract available at http://dx.doi.org/10.1001/jama.292.3.379.
Ramchandani, P. 2004. A question of balance. Nature 430(July 22):401–402.
Hershel Jick
Collaborative Drug Surveillance Program
Boston University School of Medicine
11 Muzzey Street
Lexington, MA 02421
James A. Kaye
Collaborative Drug Surveillance Program
Boston University School of Medicine
11 Muzzey Street
Lexington, MA 02421
Robert Kerwin
Department of Psychological Medicine
Institute of Psychiatry
De Crespigny Park
London SE5 9RS
England
Paul Ramchandani
Department of Psychiatry
University of Oxford
Oxford OX3 7JX
United Kingdom
Simon Wessely
Department of Psychological Medicine
Institute of Psychiatry
De Crespigny Park
London SE5 9RS
England
From Science News, Volume 166, No. 4, July 24, 2004, p. 51.