Abstract and Introduction
Abstract
Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.
Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.
Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.
Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).
Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.
Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were -31.0% (95% confidence interval -33.0% to -29.0%) among adolescents, -24.3% (-25.4% to -23.2%) among young adults, and -14.5% (-16.0% to -12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100?000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, -6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100?000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.
Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.
Introduction
Conflicting evidence on the true effects of antidepressants on suicide risk in young people has generated much controversy. Between 2003 and 2004 the US Food and Drug Administration issued several health advisories warning that children and adolescents taking antidepressants were at increased risk of suicidality (suicidal ideation and behavior). In October 2004 the FDA required a boxed warning of this risk to be on the labels of all antidepressant drugs. In May 2007 the FDA extended the warnings to include young adults.
The basis for the decision on the boxed warning has been contentious. An FDA solicited meta-analysis showed a relative risk for suicidal behavior or ideation of 1.95 (95% confidence interval 1.28 to 2.98) for young people treated with antidepressants compared with those given placebo. However, the trials included in the meta-analysis were never designed to estimate the risk of suicidality. Also, the majority of adverse events reported in the meta-analysis involved suicidal ideation, not suicide attempts or completed suicides. Despite this inconclusive evidence, the FDA advisories and the boxed warning received repeated and widespread media coverage in major newspapers and television networks. Many news stories used anecdotes and emphasized the risk of antidepressant use by children and adolescents. Thus, well intended safety warnings became frightening alarms to clinicians, parents, and young people. For example, one New York Times headline stated “FDA links drugs to being suicidal,” and another in the Washington Post reported “FDA confirms antidepressants raise children’s suicide risk.”
Suicide among young people is a devastating but preventable tragedy. In the United States in 2007, suicide was the third leading cause of death among people aged 15 to 24. Nearly 8% of high school students reported attempting suicide in 2011 and 2.4% made an attempt that required medical attention. There has been considerable concern that suicidal behavior is a potential adverse outcome of prescription drug use, including antidepressant and anticonvulsant agents.
Treating depression in young people with antidepressants can improve mood. However, the relation between antidepressant use and suicidal behavior is complex, and studies using different methods yield apparently contradictory results. Pre-existing suicidal ideation or behavior may be a precipitant for initiating antidepressant treatment. While treatment with antidepressants may reduce that pre-existing risk of suicidal ideation, this finding may not hold in young people. In adolescents and young adults, initiation of antidepressant treatment may precipitate short term increases in suicidal ideation and behavior. Given this complexity, warnings about the safety of antidepressant drugs could have unpredictable effects on drug use and suicidal behavior.
Previous studies of the FDA warnings have found substantial reductions in antidepressant treatment in children and adolescents after the warnings. The reduction even spilled over to adults, who were never a target of the warnings. The warnings were also associated with declines in depression diagnoses in children and adults. Studies reported no increase in use of treatment alternatives (for example, psychotherapy, atypical antipsychotics) among young people, and no increase in the monitoring of patients despite an explicit call for this in the boxed warning.
We investigated if the warnings and related media coverage were associated with changes in antidepressant use and suicidal behavior. Our study differs from previous studies in that it provides empirical evidence about changes in suicide attempts and completed suicides using nationwide, long term follow-up after the FDA warnings (2005-10). Because depression is an independent risk factor for suicidality, and appropriate treatment with antidepressants is effective in reducing depressive symptoms, we hypothesized that decreasing rates of overall antidepressant treatment after the warnings would be associated with a net increase in suicide attempts among young people.