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.

摘要
背景 美国食品药品监督管理局（FDA）曾发布警告，指出儿童及青少年使用选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors，SSRI）与文拉法辛会升高自杀相关风险。
目的 批判性评价支持FDA针对儿童及青少年抗抑郁药使用发布黑框警告的现有证据。
方法 针对Medline/PubMed与SciELO数据库中有关FDA抗抑郁药黑框警告、以及FDA警告对抗抑郁药处方量与自杀率影响的相关文献开展批判性综述。
结果 该警告所依据的相关调查既未报告自杀病例，也未得出能支持自杀风险升高的显著性差异结论。该概念的界定较为模糊，目前已有更多可用证据支持这一界定。选择性5-羟色胺再摄取抑制剂（SSRI）与文拉法辛的使用与更低的自杀风险相关，但因该警告导致的处方量下降反而使自杀率升高。
讨论 自杀相关行为是抑郁障碍的固有特征，因此亟需厘清该现象中有多大比例可直接归因于抗抑郁药物本身。同时也应考虑到，自杀率的升高也可能是该警告所带来的后果。