Duty to Warn: Antidepressant Black Box Suicidality Warning Is Empirically Justified

Abstract

The United States Food and Drug Administration issued a Black Box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo. Subsequently, some researchers have concluded that the Black Box warning caused severe unintended consequences; specifically, they have argued that the warning led to reduced use of antidepressants among youth, which led to more suicides. In this paper, we critically examine research regarding the Black Box warning's alleged deleterious consequences. One study claimed that controlled trials did not actually find an increased risk of suicidality among youth taking fluoxetine relative to those taking placebo, but its measure of suicidality is likely invalid. We found that ecological time series studies claiming that decreasing antidepressant prescriptions are linked to higher rates of suicide attempts or actual suicides among youth were methodologically weak. These studies exhibited shortcomings including: selective use of time points, use of only a short-term time series, lack of performing statistical analysis, not examining level of severity/impairment among participants, inability to control confounding variables, and/or use of questionable measures of suicide attempts. Further, while some time-series studies claim that increased antidepressant prescriptions are related to fewer youth suicides, more recent data suggests that increasing antidepressant prescriptions are related to more youth suicide attempts and more completed suicides among American children and adolescents. We also note that case-control studies show increased risk of suicide attempts and suicide among youth taking antidepressants, even after controlling for some relevant confounds. As clinical trials have the greatest ability to control relevant confounds, it is important to remember such trials demonstrated increased risk of suicidality adverse events among youth taking antidepressants. The Black Box warning is firmly rooted in solid data whereas attempts to claim the warning has caused harm are based on quite weak evidence.

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

“…In addition to the methodological issues in accurately estimating the prevalence and magnitude of the problem due to the fact that many trials (especially the older ones) only relied on spontaneous reports of suicidal behavior and/or ideation, we highlight here that, since the warning, there has been a decline in the prescription of antidepressants in young people, alongside an increase in the rate of suicidal events among patients with severe depression ( 4 ). These findings have been criticized by other researchers, which reported data from case-control studies that showed increased risk of suicide attempts and suicide among youth taking antidepressants, even after controlling for some relevant confounders ( 40 ). For clinical practice, one consistent finding from these reviews is that prediction of suicide is difficult and associated with uncertainty.…”

High-quality antidepressant prescribing: please consider whether “perfection is the enemy of progress”

“…While it is possible that the lack of an appropriate diagnosis reflects poor medical practice, we do not have much confidence in our medical record systems to accurately capture treatment decision-making. Reports that emphasize the potential harms of antidepressants, underestimate their potential benefit, and do not acknowledge the lack of any real evidence-based alternatives [5]. Available antidepressants are not perfect, but are much better than the prior generation.…”

Antidepressant Prescribing and Suicide/Self-Harm by Young Australians: Regulatory Warnings, Contradictory Advice, and Long-Term Trends

“…As of November 26, 2019, Google Scholar indicates this study had been cited 612 times. The Gibbons et al study's finding has thus taken on an air of established truth (4).…”

“…Using data from rather poorly designed methodology or cherry-picking data from a time series association between antidepressant prescriptions and suicide rates among youth, some have argued that regulatory warnings caused a decrease in antidepressant prescriptions, which then caused more suicides among youth (4).…”