Study finds rise in suicide attempts after FDA warning

What happened after the federal government warned a decade ago that antidepressants might raise the risk of suicidal thoughts among young people?

Instead of declining as hoped, suicide attempts over the next six years showed a “small but meaningful” uptick among people ages 10 to 29, according to a study published Wednesday in the journal BMJ. That increase followed a substantial drop in the use of antidepressants.

The study’s authors say that patients and doctors, frightened by news coverage that exaggerated the risk of antidepressants, shunned treatment that might have prevented the suicide attempts.

“Doctors should consider not just the risk of the drug, but the risk of undertreatment,” said lead author Christine Y. Lu, a researcher at Harvard Medical School’s Department of Population Medicine and the Harvard Pilgrim Health Care Institute.

Dr. Gregory K. Fritz, a psychiatry professor at Brown University who is president-elect of the American Academy of Child and Adolescent Psychiatry, called the study “well done” and “a major contribution.”

“It’s showing that what we had feared has actually happened,” Fritz said.

Other studies have documented the decline in antidepressant use, but this is the first to look at suicide attempts across the nation over many years, examining insurance data on 7.5 million people from 2000 to 2010.

It sheds new light on the aftermath of the US Food and Drug Administration’s 2004 decision to require a “black box” warning on all antidepressants to alert doctors and patients about a risk of suicidal thoughts. The black box, the FDA’s strongest warning, is a boldface advisory placed atop the package insert.

Initially, the black box emphasized the risk of suicidal thinking and behavior in children and adolescents who take the medications. The warning was revised in 2007 to recommend that doctors also consider the risk of not prescribing and called on them to monitor patients who receive the drugs.

To assess the consequences of the black box warning, the researchers looked at the rate of nonfatal drug overdoses in subsequent years. Overdoses represent only 40 percent of suicide attempts but are considered the most reliable measure of trends. The numbers showed a steady upswing in suicide attempts over the six years as antidepressant use fell 20 percent among young people. For example, in the second year after the FDA warning was adopted, overdoses increased 21.7 percent among adolescents and 33.7 percent among young adults; the increase amounts to 2 to 4 additional overdoses per 100,000 people.

The study, funded by the National Institute of Mental Health, found no increase in completed suicides nor any effect in people older than 29. The study shows an association, but does not prove that the FDA warning and news coverage caused the rise in suicide attempts. The FDA warning was based on studies in 2003 that found about 1 percent of adolescents and young adults experienced an increase in suicidal thinking after starting antidepressants. But it also came at a time of heightened concern about drug manufacturers’ influence on research and prescribing practices.

“There was a lot of concern that drug companies had manipulated data and underplayed adverse effects,” said Fritz, who is academic director of Bradley Hospital, a children’s psychiatric hospital in East Providence, R.I. “The FDA at that time was not purely doing science. They were responding to a national anxiety. It really points to the fact that you’ve got to be cautious, and there may be unintended consequences.”

Other studies have shown that despite the FDA’s recommendation, doctors did not beef up their monitoring of patients starting antidepressants. Studies also found no increase in other treatments for depression, such as psychotherapy, leading to what Fritz called “a net decrease in the amount of treatment.”

Lu, the lead author, does not blame the black box warning for the change in prescribing practices. It is more likely, she said, that doctors and patients were swayed by the news coverage, which included moving anecdotes of youngsters who attempted suicide and reporting that often confused the risk of suicidal thoughts with the risk of suicide.

“It was so intensely and widely publicized, the warning had more impact than it really should have,” she said.

Steven B. Soumerai, a coauthor and a Harvard professor of population medicine, said black box warnings typically have little effect on physician behavior, unless they are accompanied by news reports.

“Yes, it starts with the warning,” he said, “but what is really driving the behavior and the fear is more the media.”

Lu does not advocate removing the black box warning, because it alerts people to a real, if small, risk and emphasizes the importance of monitoring and the hazards of undertreatment.

In any case, the FDA said in an e-mailed statement that it has no plans to reconsider.

“At this time, nothing indicates a need for change in the boxed warning on these drugs, which urges attention to patients starting treatment, which the FDA feels is still good advice,” wrote FDA spokeswoman Sandy Walsh. “The warnings do not suggest avoiding the drugs. . . . The FDA has tried to balance the suicidality warning language with a reminder that depression is a serious illness that itself is the major risk factor for suicidal thoughts and actions.”

Antidepressant prescriptions are frequently written not by psychiatrists, but by primary care doctors: internists, pediatricians, and family doctors.

Dr. Joseph Gold — clinical director of the Child and Adolescent Program at McLean Hospital, a psychiatric hospital in Belmont — said that primary care doctors, lacking specialized training in mental health, are more likely to stop prescribing when faced with a formal warning from the FDA.

In Massachusetts, Gold added, a state-funded program enables primary care doctors to immediately consult with child psychiatrists about their patients’ mental health. As a result, he believes that Massachusetts “is in much better shape” when it comes to appropriate antidepressant prescribing.

Jeffrey A. Bridge, an Ohio State University epidemiologist who has studied the risks and benefits of pediatric antidepressant treatment, said that the decline in antidepressant use may not be the only factor.

“Fewer children and adolescents were being diagnosed with depression after the boxed warning, too, which also may have contributed to the increased rate of suicide attempts,” he wrote in e-mail.

To conduct the study, Lu and her colleagues delved into a vast database of claims from 11 health plans in the Mental Health Research Network, a consortium of not-for-profit health care organizations. The researchers tabulated the rate of nonfatal psychotropic drug poisonings from 2000 to 2010. The drugs were usually tranquilizers taken in large doses as a suicide attempt. Narcotics were not included.

Lu and Soumerai said they were not surprised that they did not find any increase in suicides, because they are so rare. But suicide attempts themselves, Soumerai noted, are not trivial: They often lead to weeks in the hospital that disrupt a young person’s life and can destroy a family’s finances.