Youth Reluctant to Seek Mental Health Care Post-Black-Box Warning on Antidepressants

Stephen Soumerai, ScD

Credit: Harvard Medical School

Ever since the US Food and Drug Administration (FDA) issued black-box warnings on antidepressants, youth have been reluctant to go on medication for their depression, a recent study found.¹

“Our goal was to assess the intended and unintended outcomes of the youth antidepressant warnings by conducting a systematic review of the most credible evidence in the field,” said lead investigator Stephen Soumerai, ScD, Harvard Medical School professor of population medicine at the Harvard Pilgrim Health Care Institute, in a statement. ² “We screened all available research reports on the warnings, focusing on those that met rigorous research design criteria and synthesized the most trustworthy data available.”

Evidence as early as 2003 has shown antidepressants may be associated with suicidal thoughts and behaviors among youth.¹ To be transparent, the FDA added this black-box Warning to antidepressants in 2005 for youth < 18. The warning was extended to individuals ≤ 24 in 2007.

The FDA hoped a black-box warning would lead people to be more self-aware of the potential risk of suicidal thoughts and behavior and monitor these symptoms. However, a systematic review discovered the warning led to a whole other outcome: the reduction of antidepressant use and increased suicide attempts and deaths.

The team screened 1841 research reports in Medline Ovid, Embase Ovid, and PsycINFO Ovid databases. Reports were all published about antidepressant warnings from January 1, 2003, to October 31, 2022. Only 11 reports met the inclusion criteria.

The study found < 5% of pediatric patients were monitored for suicidality symptoms through FDA’s contact schedule recommendations. The monitoring rate was the same as before the FDA issued the warnings. No studies observed improvements in mental health care or reductions in suicide attempts or suicides after the warnings were in place.

Not only did the warnings not impact the monitoring rate for suicidality symptoms, but fewer children and adolescents visited their doctor for depression. Four studies with a total of > 12 million patients reported substantial reductions in doctor visits for depression and depression diagnoses.

The team observed an increased use of antidepressants in the years before the FDA advisory, but after the warnings, antidepressant use reduced from 20% to 50%. A few studies also found increases in psychotropic drug poisonings, a proxy for suicide attempts, and suicide deaths.

“Contrary to the FDA’s intent to increase physician monitoring of suicidal thoughts and behaviors of treated patients, a large longitudinal study suggests that this did not occur,” investigators wrote.

The team wrote the validity of the review could be threatened by the possibility that other events or forces other than the warnings, such as increased social media use, the opioid epidemic, and the 2008 recession, resulted in increases in psychotropic drug poisonings and suicide deaths. However, after considering these events, they decided these were not likely to be confounders. Social media’s impact on mental health was minimal at the time of the FDA warnings, trends saw when opioid deaths were up suicides were down, and research had demonstrated that recessions were not likely to affect the mental health of anyone who was not middle-aged.

Investigators recognized that it is unlikely for a single outside factor to be the reason for the ripple effects of depression care, suicidal behavior, and suicide death.

“The sudden, simultaneous, and sweeping effects of these warnings––the reduction in depression treatment and increase in suicide––are documented across 14 years of strong research,” Soumerai said.² The consistency in observed harms and absence of observed benefits after the black-box warnings indicate this is not a coincidence. We recommend that the FDA consider incorporating the black-box warnings into the list of routine warnings that pose fewer health risks, or potentially removing the warnings altogether.”

References

1. ^{Soumerai, S, Kappel, R, Naci, H, et al. Intended and Unintended Outcomes After FDA Pediatric Antidepressant Warnings: A Systematic Review. Health Affairs. 2024. doi:10.1377/hlthaff.2023.0026.}
2. ^{Systematic review highlights decline in mental health care and increase in suicides following FDA youth antidepressant warnings. EurekAlert! October 7, 2024. https://www.eurekalert.org/news-releases/1060134?. Accessed October 7, 2024.}