Three new studies come to conflicting conclusions about risks for suicidal behavior associated with antidepressants such as Paxil, Prozac and Zoloft.

These and other selective serotonin reuptake inhibitor (SSRI ) medications have come under close scrutiny over the past year as isolated reports surfaced of adolescent users either killing themselves or attempting suicide while on the drugs.

However, these three new studies are not likely to clear up the confusion on this issue.

Together they “send a variable signal about increased suicidal behavior,” said Dr. John Geddes, a professor of epidemiological psychiatry at the University of Oxford in England and co-author of an editorial accompanying the reports in the Feb. 19 issue of the British Medical Journal.

There is a “small but real risk” associated with their use, Geddes believes, and “the balance between benefits and risk probably is less favorable in the younger age group.” However, SSRIs should not be ruled out automatically, but rather the balance should be weighed case by case, he said.

The possibility that antidepressant drugs, particularly SSRIs, increase the risk of suicide in younger people has become a hotly debated issue.

Last year, British authorities declared children and adolescents should be given no antidepressants other than Prozac. In October, the U.S. Food and Drug Administration told drug companies to put a “black box” warning label on the medications, cautioning doctors and consumers of the potential risk for suicidal thoughts or behavior in pediatric patients.

The three new studies approach the issue from different angles. The largest, conducted at the Medicines and Healthcare Products Regulatory Agency in London, looked at data on more than 146,000 people taking either SSRIs or older tricyclic antidepressants in the United Kingdom.

That study found “no evidence that the risk of suicide or non-fatal self-harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants,” its authors wrote. But they did note “some weak evidence” of such behavior in SSRI users aged 18 or younger.

A second study looked at data on more than 40,000 people taking part in 477 controlled trials. “We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded,” wrote the researchers, from the University of Bristol in England, who did the study. They, too, said they detected “weak” evidence of an increased risk of self-harm.

“Larger trials with longer follow-up are required to assess the balance of risks and benefits fully,” they concluded.

The third study, amassed data on close to 88,000 participants enrolled in 702 clinical trials. It found a “significant increase in the odds of suicide attempts,” which were found to be twice as likely in people taking SSRIs than in those taking a placebo.

“The clinical implications are that we have good evidence that there is a rare but serious risk associated with SSRIs,” said study author Dean Fergusson, a scientist at the Ottawa Health Research Institute in Ontario. “This information needs to be relayed to physicians and patients.”

“But the risk has to be put into perspective,” Fergusson added. “There are benefits as well as risks associated with these medications.”

A more positive assessment of the results came from Dr. David Fassoer, a trustee of the American Psychiatric Association.

“What these results suggest is that patients who take antidepressant medications will be more likely to talk about their suicidal thoughts or tell someone about their suicidal attempts,” Fassoer said.

One problem in interpreting meta-analyses (reviews of data from a wide number of studies) such as those now being reported is that “it is difficult to tease out the methodological details in the underlying studies,” Fassoer said. However, he said the finding that suicidal thoughts and attempts were reported at a higher rate among people taking the medications is valuable information.

“As a clinician, I’m most concerned about patients who have suicidal thoughts and don’t tell about them,” Fassoer said. “Taking antidepressants increases the likelihood that they will tell [someone] about it and hopefully get additional help and support.”

Fergusson added that another difficulty in assessing this information is that most of the trials were relatively short-term, lasting an average of just 10 weeks.

“My take is that we need a large, long-term trial to assess both benefits and risks,” he said. “This needs to be put at the top of our agenda.”

SOURCES: John Geddes, M.D., professor, epidemiological psychiatry, University of Oxford, England; Dean Fergusson, scientist, Ottawa Health Research Institute, Ontario; David Fassoer, M.D., trustee, American Psychiatric Association, and private practitioner, Burlington, Vt.; Feb. 19, 2005, British Medical Journal