FDA Warning About Antidepressants Followed by Drop in Use, and Increase in Suicide Attempts
A decade ago the Federal Drug Administration (FDA) released several warnings that children, adolescents (ages 10–17), and young adults (ages 18-29) taking antidepressants were at increased risk for suicidal ideation and behavior. A recent study found that following these warnings, antidepressant use among adolescents, young adults, and adults dropped, and psychotropic drug poisonings (a validated measure of suicide attempts) increased among adolescents and young adults. Numbers of completed suicides did not change for any age group.
The decision to place the warnings on antidepressant packaging was somewhat controversial because it was based on studies that were not necessarily designed to measure suicide risk. The relationship between depression, medication, and suicide is complicated. Medication can improve mood, but patients may seek out medication because of pre-existing suicidal thoughts, and the medication may not reduce these in young people.
The reduction in antidepressant use that occurred after the warnings was accompanied by a drop in depression diagnoses in children and adults. Studies have suggested that the decreases in antidepressant were not accompanied by increases in other treatments, such as psychotherapy or atypical antipsychotics, among young people. Increased monitoring of patients was called for in the FDA’s box warning, but did not take place.
The study of the aftermath of the FDA warnings, published by Christine Y. Lu et al. in a 2014 article in the journal BMJ, used data from 11 insurance networks throughout the US. The researchers used an interrupted time series study design, which is used to show whether a policy causes an abrupt change in the expected slope of study outcomes. Data covered the pre-warning period (first quarter of 2000 to third quarter of 2003), the warning “phase-in” period (last quarter of 2003 to last quarter of 2004) and the post-warning period (first quarter of 2005 to last quarter of 2010). The study cohorts included around 1.1 million adolescents, 1.4 million young adults, and 5 millions adults per quarter.
Among adolescents, the previously upward trend in antidepressant use declined by 31.0% in the second year after the warnings, and psychotropic drug poisonings increased by 21.7% (a figure that was statistically significant for males). Poisonings by any drug increased by 13.9% in the second year after the warnings. After 2008, the downward trend in antidepressant use reversed, indicating that either the initial effects of the warning had worn off or that modifications to the warnings in May 2007, which encouraged patients and doctors to consider the risk of antidepressants alongside the risk of leaving mood disorders untreated, led to increased use.
Among young adults, the upward trend in antidepressant use declined by 24.3% in the second year after the warnings, and psychotropic drug poisonings increased by 33.7%, a statistically significant change for both male and female patients.
Among adults, to whom the warnings were not directed, antidepressant use decreased by 14.5% in the second year after the warnings.
The study by Yu et al. is the first to show that suicide attempts actually increased after the FDA warnings. The authors suggest that the increase in suicide attempts might be a consequence of undertreating mood disorders, since antidepressant use dropped simultaneously. The warnings and related media attention may have led to these unintended consequences, since media reports can sometimes be oversimplified.
