Will SSRI suicide fear curtail appropriate use?

Washington -- A move last month to broaden the age range for label warnings on risks of suicidal thoughts and behaviors associated with antidepressant use reignited concern about the impact such cautions may have on the continued proper use of these drugs.

The controversy has been raging in recent years, and alarms have been set off again by new data showing that prescribing rates for antidepressants -- including the popular selective serotonin reuptake inhibitors -- have declined, especially for children, while suicide rates may be climbing.

U.S. suicide rates in children up to 18 increased from 1.76 per 100,000 in 2003, when this issue first surfaced, to 2.01 per 100,000 in 2004, according to the Centers for Disease Control and Prevention. Suicides also increased in the Netherlands after a similar controversy over the drugs' side effects, according to testimony at a Food and Drug Administration hearing last month.

Such data lead some experts to say that heightened warnings of possible side effects among children and teens, which were added to SSRI labels in 2004, have made increasing numbers of doctors reluctant to prescribe the drugs. This outcome, they add, is causing patients more harm than good.

The FDA advisory committee also heard testimony in mid-December 2006 about the risks and benefits of antidepressant use for adult patients. There were numerous, deeply affecting stories about the suicides of loved ones who were taking the drugs. But there also were pleas from physicians that the use of these medications, which have been shown to be effective, should not be discouraged.

The committee ultimately voted to advise the FDA to extend warnings about the use of the medications to include patients up to age 25, but not older. Agency officials generally follow panel recommendations, although no final decision on label changes had been released by early January.

Regardless of what becomes of the proposed label changes, some experts and researchers say physicians should not view expanded warnings as a reason to shy away from prescribing these drugs appropriately.

"We know there is a clear association between declining suicide rates around the world and the increased use of SSRIs," said Kelly Posner, PhD, assistant professor of clinical psychiatry at Columbia University's College of Physicians and Surgeons in New York City. Dr. Posner was principal investigator for a joint FDA-Columbia review of antidepressant use among children that was considered when the initial label warning was added.

That review showed an increase in the number of suicidal thoughts and behaviors among children taking antidepressants. But it documented no completed suicides.

A note of caution

In a recent interview, Dr. Posner urged caution in interpreting those findings, because the studies she and her colleagues examined were not set up to look specifically at suicidal behaviors and thoughts, but at adverse events in general.

There could be a number of explanations for increases in such suicidal ideation, she added. "People on active medication have more side effects, more stomachaches and headaches, so they may just have more face time with the doctor to report a suicidal thought or behavior, rather than there being a true difference in risk caused by the medication."

A decline in prescribing rates also has troubled many in the mental health field. "Since prescription rates have dropped -- by more than 25% for children -- we have been afraid that this has been some horrible natural experiment that would result in completed suicide rates starting to go up again," Dr. Posner said. "And that's what's happening."

Untreated depression does take a toll, said David Fassler, MD, clinical professor of psychiatry at the University of Vermont in Burlington. "It can have a devastating impact on a person's ability to function at home, in school and at work. It also has a significant impact on morbidity and mortality due to increased risk of other medical illnesses as well as the risk of suicide attempts and actual death attributable to suicide."

The AMA also has expressed concern about the possible effect on prescribing habits of black-box warnings and urged the FDA to study how label changes might affect the way physicians and patients use the drugs.

Nada Stotland, MD, MPH, a Chicago psychiatrist and vice president of the American Psychiatric Assn., said the terms "suicidal ideation" and "suicidal behavior," which are used in the medication's label, can be mistaken for completed suicide, although they are very different.

Suicidal ideation is not uncommon, she noted. "And we would prefer to have [patients] tell us about it so we could intervene to help them with whatever is troubling them."

The essential fact to keep in mind, she said, is that no suicides took place among the children who participated in the studies on which the first round of warnings were based.

Nor is there enough information on completed suicides among adults to draw conclusions about that potential outcome, said Thomas Laughren, MD, director of FDA's division of psychiatry products, during a media briefing following the advisory committee meeting.

Meanwhile, physicians are being strongly advised by the FDA to monitor closely patients who begin taking antidepressants. This is a step many skip, several studies said. A physician should speak to a patient, or a family member, within two or three days of prescribing an antidepressant, Dr. Stotland noted. "This can be a five-minute phone call to ask whether the medication caused a stomach problem, a headache or trouble sleeping.

"In addition," she said, "you will see that patient in a week or two."