Pediatrics
Lauren Howell, PharmD
The findings from a systematic review published in the October 2024 issue of Health Affairs revealed that there may be a need for the reevaluation of risks and benefits of the boxed warnings that FDA has applied to antidepressants. The review found that these warnings, originally implemented to increase physician monitoring of suicidal thoughts and behaviors, may actually cause reductions in mental health care and increases in psychotropic drug poisonings and suicide deaths.
In 2003, FDA posted an advisory warning stating that antidepressants may be associated with suicidality in patients younger than 18 years old soon after treatment is initiated. In 2005, FDA began requiring a boxed warning of this risk on product labels and advertisements for all antidepressant drugs. In 2007, this warning was expanded to young adults up to and including 24 years old. The 2007 warning is still the one that is in use today.
The systematic review
The goal of the systematic review was to evaluate the relationship between FDA antidepressant warnings and changes in care and outcomes among youth. Outcomes included the intended outcome of the warnings, which was monitoring for youth suicidality, as well as other potential outcomes, including changes in physician visits for depression, depression diagnoses, psychotherapy visits, antidepressant treatment and use, psychotropic drug poisoning (a proxy for suicide attempts), and suicide deaths.
To conduct the review, researchers identified 11 investigations published in peer-reviewed literature on changes in youth outcomes associated with the FDA antidepressant boxed warnings. The studies that were included in the review were based on data from state Medicaid programs, death certificates for all U.S. counties captured in the CDC Wide-Ranging Online Data for Epidemiologic Research database, nationwide managed care plan data sets, and nationally representative surveys.
Results and findings
Multiple studies reported substantial reductions in physician visits for depression and depression diagnoses, reductions in antidepressant treatment and use, and increases in psychotropic drug poisonings and suicide deaths among pediatric patients. Out of all the reported findings from the included studies, there were none that indicated intended or desirable outcomes from the antidepressant warnings; 35 findings indicated unintended or adverse outcomes; and eight findings indicated neutral outcomes.
While the intent of the warnings was to increase monitoring of pediatric patients while on antidepressant therapy, based on the review, less than 5% of pediatric patients were monitored in accordance with FDA’s contact schedule recommendations. This rate was unchanged from the rate before the warnings were implemented.
The studies in the review also found sudden and substantial declines in physician visits for depression and depression diagnoses after the FDA warnings were issued. Some studies showed increases in physician visits for depression and depression diagnoses in the years before the warnings were issued and declines ranging from 20% to 45% afterward.
Several studies included in the review reported evidence of a decline in antidepressant treatment and use in the pediatric population following the introduction of boxed warnings. Declines were also seen among the adult population, despite the fact that the warnings did not apply to this age group.
One study found that when an organization attempted to increase monitoring of suicidality after the FDA advisory by requiring preauthorization of antidepressant refills, the amount of new prescriptions that had any refills declined by about half and the duration of use declined.
Moving forward
The results of the studies included in the systematic review revealed that boxed warnings for antidepressants may not be accomplishing their intended goal and may actually be making the situation worse. The authors of the review concluded that FDA officials should review the evidence and acknowledge possible harms of the antidepressant warnings.
As one of the most accessible health care providers for many individuals, pharmacists can help their patients to understand the meaning of these warnings and counsel them based on any of their fears about taking an antidepressant medication. Additionally, pharmacists can screen for depression and refer patients to mental health care as needed. ■