Studies continue to raise questions about the risk of suicide in patients treated with antidepressant drugs. The studies also show that different antidepressants have the same suicide risk (search).

In 2004, the FDA concluded that antidepressant medications (search) increase the risk of suicidal thinking and behavior in children and adolescents with depression (search). Studies continue to show that this link exists even in adults treated for depression.

A new review bolsters claims of an increased risk of suicidal behavior in people taking the most popular antidepressants, but a second trial found no increase in such risk among depressed patients taking selective-serotonin reuptake inhibitors (search) (SSRIs).

A third study showed the risk of suicidal behavior to be no greater in patients taking SSRIs than in those taking an older class of antidepressants.

The three studies are published in the Feb. 19 issue of the BMJ.

They offer somewhat contradictory findings that seem to raise as many questions as they answer.

“I think there remains uncertainty about this question and there will continue to be uncertainty,” psychiatry research fellow Andrea Cipriani, tells WebMD.

Researchers Agree on Key Points

While the emerging evidence fails to give definitive answers about the risks of suicide in depressed people taking Prozac (search), Paxil (search), Zoloft (search), or the other SSRIs, the researchers contacted by WebMD agreed on several key points, including:

Untreated moderate-to-severe depression in adults appears to pose a bigger suicide risk than SSRI use. The benefits are less clear in children and adolescents, however. In an editorial accompanying the three studies, Cipriani wrote that the lack of long-term safety data “should discourage the routine prescribing of antidepressant drugs in children and adolescents.”

If there is an increased risk of suicidal behavior in people taking SSRIs, it seems to be greatest early in treatment. All agreed that patients should be closely monitored during this time.

Risk does not appear to be limited to this particular class of drugs.

In one of the newly published studies, researchers assessed the risk of self-harm and suicide among 146,000 patients taking either SSRIs or tricyclic antidepressants.

They found that the SSRIs and tricyclics, such as Elavil, Norpramin, or Pamelor, had similar risk profiles with regard to suicide and self-harm in adults. Children and adolescents who took SSRIs appeared to be at slightly greater risk for self-harm, but none of the children in the study actually committed suicide.

“Our finding that SSRIs and tricyclic antidepressants (search) have a similar risk profile with respect to self-harm and nonfatal self-harm is reassuring,” researcher Carlos Martinez, PhD, and colleagues from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency wrote.

“It is possible, however, that any adverse or protective effects are common to all classes of antidepressants.”

Largest Study Shows Twofold Increase in Risk

In the largest of the reviews, researchers reported a twofold increase in the rate of suicide attempts in patients taking SSRIs compared with those taking a placebo.

Researcher Dean Fergusson, PhD, and colleagues from Canada’s Ottawa Health Research Institute analyzed 700 studies involving more than 87,000 patients.

The large analysis also showed no difference in suicidal behavior among patients taking SSRIs and tricyclic antidepressants.

Fergusson tells WebMD that while the overall rate of suicide attempts was low -- roughly four attempts for every 1,000 people treated -- the widespread use of SSRIs makes the issue a significant public health concern.

“The message for psychiatrists and family docs prescribing these drugs is that even though they have a lot of benefits, the risks need to be included in their discussions with patients,” he says.

Another group of researchers assessed pharmaceutical company data on safety from the U.K.’s Medicine and Healthcare products Regulatory Agency. It included more than 40,000 people who took part in 477 separate studies. There were 16 suicides, 172 incidences of nonfatal self-harm and 177 incidences of suicidal thoughts reported among the patients.

Researchers found no evidence that SSRI use increased the risk of suicide or suicidal thoughts more than placebo treatment.

But the authors concluded that an increased risk associated with SSRI use “cannot be ruled out.”

“[Our analysis] suggested an underreporting of self-harm and probably suicidal thoughts,” researcher David Gunnell, PhD, tells WebMD.

All of the researchers agreed that larger trials that follow patients for longer periods are needed to better understand the risks and benefits of the SSRIs.

By Salynn Boyles, reviewed by Brunilda Nazario, MD

SOURCES: Fergusson et al., Martinez et al., Gunnell et al. BMJ, Feb. 19, 2005; vol 330: pp 385-388, 389-393, 396-399. David Gunnell, MSc, PhD, department of social medicine, University of Bristol, U.K. Dean Fergusson, PhD, epidemiologist, Ottawa Health Research Institute, Ontario, Canada. Andrea Cipriani, research fellow in psychiatry, department of medicine and public health, University of Verona, Italy.