The FDA “Black Box” Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits?

Michele Fornaro,Alessandro Carano,Federica Vellante,Luigi Olivieri,Giampaolo Perna,Gabriella Rapini,Domenico De Berardis,Annalisa Anastasia,Alessandro Valchera,Massimo Di Giannantonio,Serena Di Natale,Giovanni Martinotti,Laura Orsolini

doi:10.3389/fpsyt.2019.00294

Abstract

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.

Highlights

Suicidal behavior accounts for remarkably high rates of mortality and morbidity worldwide
Based on anecdotal reports suggesting an inflated rates of suicidal behavior among Major Depressive Disorder (MDD) patients exposed to the Selective Serotonin Reuptake Inhibitors (SSRIs) [10], beginning from October 2003, the U.S Food and Drug Administration (FDA) issued a series of health advisories and warnings for children and adolescents prescribed with antidepressant drugs [11]
The two case reports briefly presented add to the relatively scarce evidence available in the literature about the potential consequences of over-concern raised by the FDA black-box warning on antidepressant and suicide

Summary

INTRODUCTION

Suicidal behavior ( including completed suicide and non-fatal suicide attempts) accounts for remarkably high rates of mortality and morbidity worldwide. Based on anecdotal reports suggesting an inflated rates of suicidal behavior among MDD patients exposed to the Selective Serotonin Reuptake Inhibitors (SSRIs) [10], beginning from October 2003, the U.S Food and Drug Administration (FDA) issued a series of health advisories and warnings for children and adolescents prescribed with antidepressant drugs [11]. Such a claim was supported by a subsequent, controversial meta-analytic report of industry-sponsored trials on pediatric patients [12]. Despite the increasing body of evidence contrasting the strict regulatory rules enforced by the FDA, the agency seems reluctant to retract the black box warning [14], even if that claim may rely on miscalculations, or it may not fit the real-world practice, as documented in the case reports outlined in the following lines

CASE REPORTS

Findings

DISCUSSION