For nearly two decades, antidepressants have carried black box warnings linking them to an increased risk of suicidal thoughts and behaviors in young people. Contradictory to expectations, research suggests these warnings may have had unintended consequences, leading to fewer depression diagnoses, reduced prescriptions, and, paradoxically, higher suicide rates.
With accumulating evidence pointing to these negative outcomes, some healthcare professionals and researchers are advocating for the US Food and Drug Administration (FDA) to reconsider or eliminate these warnings.
The Black Box Warnings Controversy
In October, a Health Affairs report reviewed studies from 2003 to 2022, revealing a significant drop in physician visits for depression, ranging from 20% to 40%, and a decline in antidepressant use by 20% to 50%. Following the warnings, there was also a noticeable rise in psychotropic drug poisonings and suicides.
Lead author Stephen Soumerai, ScD, a professor of population medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, called for the FDA to review the evidence comprehensively. He proposed replacing the boxed warnings with a more routine warning in labeling.
Impact on Treatment and Medication Prescriptions
The FDA first issued warnings about potential suicidal thoughts and behaviors in children in 2003. In 2005, following an advisory panel, the agency added black box warnings to all antidepressants for children under 18. These warnings were later expanded to include young adults up to 24 years old in 2007.
Soon after the warnings, in 2009, Medscape Medical News reported a sharp decline in pediatric depression diagnoses, with primary care physicians diagnosing 44% fewer cases than before.
Richard A. Friedman, MD, a professor at Weill Cornell Medicine, argued in 2014 that the boxed warnings had detrimental effects and recommended their removal.
Jeffrey Strawn, MD, a professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine, has conducted numerous studies on the topic. He provided a systematic review in 2014 and a meta-analysis showing that antidepressants were more effective than placebos, with no higher risk of suicidal behavior.
Strawn noted that the risk might be associated with specific medication types, such as paroxetine and venlafaxine, and can be influenced by other factors including the patient’s baseline mental health.
Dara Sakolsky, MD, PhD, an associate professor of psychiatry at the University of Pittsburgh School of Medicine, agreed that the current warnings have had negative unintended effects. She suggested the FDA tone down the warnings by移到标签说明中.
The Risks of Ignoring Youth Depression
Despite compelling arguments for revising the warnings, some clinicians remain cautious. Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, emphasized the importance of considering the benefits of antidepressants against the risk of suicidal behavior.
Depression is a significant mental health issue for those under 25 years old. The prevalence has increased more among adolescents than adults, and depression is strongly associated with suicide.
The National Institute of Mental Health reported in 2021 that suicide is the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.
John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine, highlighted that untreated depression poses a severe risk. “Suicide kills more kids aged 10 to 24 than cancer and all other illnesses combined,” he emphasized.
Landmark studies, such as the Treatment for Adolescents with Depression Study in 2007, demonstrated that fluoxetine, particularly in combination with cognitive-behavioral therapy (CBT), was significantly more effective than a placebo.
Reevaluating the Evidence
When the FDA instituted the warnings in 2005, it was based on a combined analysis of 24 trials involving over 4400 patients. The risk of suicidal thoughts or behaviors was reported to be 4% for those taking antidepressants, compared to 2% for the placebo group. Notably, no suicides occurred in these trials.
However, the observational nature of recent studies makes it challenging to establish a direct cause-and-effect relationship. The FDA evaluates such studies as part of its broader evidence base.
Alicia Ault, the author of this report, noted that more recent studies might reflect changes in practice. In 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18. Sakolsky has observed more referrals to her clinic as a result.
Strawn believes that the time has come to reassess the warnings. “Withholding effective treatments can lead to tragic outcomes,” he stated.
Next Steps for the FDA
The FDA maintains a stance that it does not comment on individual studies but reviews them for public health protection. Bridge suggested a new meta-analysis would provide valuable insights for reevaluation.
Campo acknowledged the challenges in changing the warnings after such a long period. “It’s difficult to reverse policies that have been in place for so long, but new evidence should be carefully considered,” he said.
As the conversation continues, the key lies in balancing the risk of untreated depression against the potential side effects of antidepressants. Healthcare providers must be informed by evidence rather than precautions.
Conclusion
The debate over antidepressant warnings in young people revolves around protecting public health while ensuring access to effective treatments. The FDA’s careful review of recent research can help guide this complex decision.
With depression prevalence on the rise and suicide rates troublingly high among youth, it’s crucial that medical practices evolve to benefit patient care.
We urge the FDA to consider this comprehensive evidence and continue its commitment to ensuring the best possible outcomes for young patients.
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