July 20, 2004 — Suicidal behavior isn’t any more common in adults and teens taking SSRI-type antidepressants than in those taking tricyclic antidepressants, a look-back study shows.

However, a new study shows a fourfold increase in nonfatal suicidal behavior during the first nine days of treatment with any of four different antidepressants — two SSRIs (Prozac and Paxil) and two tricyclics (Elavil and dothiepin; the latter is not sold in the U.S.). This risk remains three times higher during days 10-29 of treatment than after 90 days of treatment.

Fatal suicide is 38 times more likely during the first nine days of treatment. However, none of the 10- to 19-year-old patients in the study committed suicide.

Recent reports have shown that the newer SSRI antidepressants may increase suicide risk in teens and even in adults. The U.S. FDA recently warned doctors prescribing any antidepressant drugs — not just SSRIs — to keep a close eye on patients for possible suicidal behavior.

The report in the July 21 issue of the Journal of the American Medical Association makes this seem like very wise advice, says study co-author James A. Kaye, MD, DrPH. Kaye is senior epidemiologist for the Boston Collaborative Drug surveillance program and associate professor at the Boston University School of Public Health.

“The issue really is whether the risk for suicide behavior and suicide itself varies among the users of these different drugs. We found there were not major differences,” Kaye tells WebMD. “Yet the time period after starting any of these treatments is a high-risk period. We agree that there should be careful monitoring of patients who have started on these drugs, as the FDA has already advised.”

The findings are “moderately reassuring,” says Simon Wessely, MD, professor of psychiatry at King’s College School of Medicine and the Institute of Psychiatry, London.

“This study reminds us that depression itself is linked to deliberate self-harm,” Wessely tells WebMD. “And it tells us that SSRIs have no more effect on suicide than any other antidepressant drug. So if there is an association between antidepressant drugs and suicidal behavior, it is no different for any of the antidepressants.”

So why the big jump in suicide and suicidal behavior soon after patients start treatment? Wessely compares people who seek help for depression to people who seek help for chest pain. Both types of patient tend to see the doctor only when they are in bad shape.

“So a lot of people go to see their doctor when they are at their worst,” Wessely says. “This study was not designed to detect whether antidepressants make that risk even worse. But it does suggest that not one of them elevates the risk more than the others.”

Teen Suicide Risk Not Higher With SSRIs

Kaye and colleagues based their study on a huge U.K. database. It contains detailed information on nearly 160,000 patients who took any of four antidepressant drugs from 1993-1999. During these years, dothiepin was the most commonly prescribed antidepressant in the U.K. The researchers compared suicidal behavior in patients who took dothiepin to that of patients taking Elavil, Prozac, or Paxil.

There’s been particular worry about suicidal thoughts and actions in teens taking antidepressant drugs. So the researchers also combed through the huge database — which includes some 5% of the U.K. population — to look for teenage suicides.

“We saw similar findings in teens to what we saw in general,” Kaye says. “We looked at teens who had taken only one of these drugs and had not had previous suicidal thoughts or behavior. And we looked at the whole population in the database to see if we could find any teens who had committed suicide. Of the 15 teens who did commit suicide, none had been on any antidepressants.”

This doesn’t mean that all teens with depression should be put on antidepressants, Kaye is quick to note. Why there weren’t any suicides among kids taking antidepressants has yet to be explained.

“It may be that teens are different, or that doctors are reluctant to prescribe antidepressants for high-suicide-risk teens,” Kay says. “Whatever the explanation is, we didn’t see any teens who were treated with antidepressants and committed suicide. It doesn’t look like that is a major problem on a population bases, although there could be individual situations outside of the data we covered. It doesn’t appear to be a major problem.”

Paxil Risk Higher — but Higher-Risk Patients May Get Newest Drug

There was a trend for patients starting treatment with one of the SSRIs in the study — Paxil — to exhibit more suicidal behavior. The finding wasn’t statistically significant, meaning that it could be a chance finding. On the other hand, Kaye notes, it’s likely that patients at the highest risk of suicide were given the newest antidepressants.

Why? One way patients try to kill themselves is by drug overdose. And in this regard, tricyclic antidepressants are more dangerous than SSRIs.

“Many psychiatrists, when they have a very risky patient, prescribe SSRIs because they are safer if a patient becomes suicidal and tries to take an overdose,” Wessely says. “So Paxil is perhaps a bit more linked to suicide, but probably that is because SSRIs are prescribed to the most risky patients.”

That doesn’t mean SSRIs get a totally clean bill of health, however.

“SSRIs do cause side effects. It remains the case that some people may react badly,” Wessely warns. “There may still be an indirect link between SSRIs and suicide. For example, take the SSRI side effects of weight gain and agitation, seen in some people. Such side effects may further disturb patients and increase their risk of suicide. So while there seems to be no direct link between SSRIs and suicide, there may well be indirect relationships.”

The bottom line: Anyone with clinical depression is at increased risk of suicide. Any patient beginning treatment with any antidepressant — as the FDA advises — needs careful monitoring.