Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

Abstract

Background: The United States Food and Drug Administration (FDA) has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI) and venlafaxine in children and adolescents. Objectives: To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods: A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results: The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion: Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

Treatment of Major Depressive Disorder in Pediatric Populations

“…However, only about 60% of pediatric MDD patients respond to fluoxetine [ 17 ], and there may be a potential increased risk of suicide attempts and suicides carried out in pediatric patients treated with SSRIs [ 29 , 32 , 35 , 36 ]. However, suicidality is a symptom of pediatric MDD, and the potentially small increase in suicide attempt risk may not outweigh the benefit of treatment on a population level [ 37 , 39 , 40 ]. Due to challenges in effectively diagnosing pediatric patients with MDD, screening all pediatric patients may provide more comprehensive coverage of pediatric patients who require treatment [ 13 ].…”

“…However, these findings have not been consistent across all studies. It is important to note that suicide risk is already increased in pediatric MDD patients, and the risk of not treating pediatric MDD patients who require treatment may outweigh the potentially small increased risk of suicide attempt with SSRI treatment on a population level [ 37 , 39 , 40 ]. Given the evidence for a potential increase in suicide risk during SSRI therapy, the FDA recommends that pediatric MDD patients treated with fluoxetine or escitalopram be monitored on a weekly basis for the first month and then biweekly for another month, in order to help alleviate any increased risk of suicide that may be incurred by fluoxetine treatment [ 20 , 28 ].…”

Critique of Psychiatry in Rural and Remote Communities

“…They fundamentally change the architecture and physiology of the brain and thus the mind. When black box warnings were added to the antidepressant class of selective serotonin reuptake inhibitors (SSRIs) and physicians began to take adolescents and children off the medications, pre-and post-insurance data analytics found that there were statistically significant increases in suicide, the very thing the warnings were trying to prevent, which describes the prescriber's dilemma (Martínez-Aguayo et al 2016). Action in either direction can increase the risk of suicide.…”

Study 329 and the use of paroxetine in child and adolescent unipolar depression

“…We have recently published the article "Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review" regarding the warning issued in 2003 by the United States Food and Drug Administration (FDA) about the use of serotonin reuptake inhibitors and venlafaxine for the treatment of child and adolescent depression, and its association to an increased suicidality risk 1 . However, considering the new evidence emerged on the topic, we would like to update our article using new available information regarding paroxetine use, a serotonin reuptake inhibitor involved in FDA's warning as well.…”

“…The authors highlighted the need of making primary trial data and protocols available to increase the thoroughness of the evidence. In our study, Study 329 was not included, and neither was its reanalysis 1 .…”