NEW YORK – A widely publicized warning by U.S. regulators a decade ago about risks for teens taking antidepressants led to plummeting prescriptions and increased suicide attempts, Harvard University researchers said.
As the public took the Food and Drug Administration’s (FDA) 2004 warning to heart, adolescent attempted suicides increased 21.7 percent and a 31 percent decline in antidepressant use was seen two years later, according to research published last week in BMJ, formerly the British Medical Journal. Attempted suicides among those aged 18 to 29 increased 33.7 percent.
The effect of a regulatory warning that gained wide attention in the media shows the need for better communication by public health professionals, said Christine Lu, the study’s lead author. The drop in antidepressant prescriptions among adolescents and young adults probably means depression went untreated, she said.
“After the widely publicized warnings we saw a substantial reduction in antidepressant use in all age groups,” said Lu, an instructor in population medicine at Harvard Pilgrim Health Care Institute, in a telephone interview. “Warnings, especially widely publicized warnings, may have unintended consequences.”
After a review of clinical trial data in 2003, the FDA required drug makers to add a “black box” warning, the agency’s strictest alert, about risks of suicidal thoughts or actions among children and adolescents taking the antidepressants.
The assertion of a direct link between the FDA warning and increased psychotropic drug poisonings doesn’t convince Marc Stone, a senior medical reviewer at the FDA, who spoke on his own behalf.
“It’s a stretch to say that the people that are committing suicide or the increase in suicide attempts has to do with the prescription of antidepressants,” Stone said in a telephone interview. “There’s absolutely nothing in the study to say that these are the people who would have been prescribed the antidepressants if it weren’t for the warnings.”
Lu said the focus by the media on the risk of suicide, even though the review of data found no increase in completed suicides, frightened patients and parents.
“The warning covered the necessary information for clinicians and patients and the public,” Lu said. “In news reports the emphasis was on the risk of completed suicide. I think that’s alarming for parents and patients and clinicians to see.”
Antidepressant use had been increasing as a new class of drugs, selective serotonin reuptake inhibitors or SSRIs, became available in the 1980s and 1990s. Eli Lilly & Co.’s Prozac, Pfizer Inc.’s Zoloft and GlaxoSmithKline Plc’s Paxil are SSRIs. About 1 in 10 Americans were taking antidepressants from 2005 to 2008, according to the most recent report by the U.S. National Center for Health Statistics.
In today’s study, researchers analyzed claims data from 11 health plans of 7.5 million individuals from 2000 to 2010. The study used drug poisonings as a proxy for suicide attempts. The rate of completed suicides didn’t change. Previous research has also found a decline in antidepressant use among adolescents following the FDA warnings.
Balancing a possible side effect of the antidepressants with the risks of untreated depression is what the FDA tried to do with its warning, Sandy Walsh, a spokeswoman for the agency, said in an email.
“The warnings on the drugs do not say not to treat depression,” Walsh said. “They say suicidality is a risk in young people, and so the clinician should monitor the young patient when starting or increasing the dose, of these drugs.”
There are other issues that could be influencing the drop in antidepressant prescription and rise in poisonings, Stone said. The data presented in the study shows a steady increase before the warnings in antidepressant prescription rates for adolescents, while drug poisonings remained relatively steady. The rise in poisonings after the warnings, when prescriptions declined slightly in that group, doesn’t show a link between the two events, he said.
“They’re describing a very strange phenomenon in society that’s supposedly being held back by antidepressant use,” Stone said. “It doesn’t stand up to what we know about the mental health situation in the United States.”
Others said the “black box” warning was unnecessary.
Suicidal thoughts are common symptoms of depression, so antidepressants don’t necessarily cause suicidal thoughts or attempts, said Greg Fritz, the president-elect of the American Academy of Child and Adolescent Psychiatry.
The “black box” warning “was an overreaction and it had undesired consequences that there was a huge drop in the prescription of antidepressants,” Fritz said. “This is the first definitive study to show that there was an increase in suicide attempts.”