Too Many Avoidable Suicides Occur Worldwide in Young Patients.

Klaus Rose,Jane M Grant-Kels,David Neubauer

doi:10.5041/rmmj.10374

Abstract

United States (US) and European Union (EU) laws attempt to counterbalance the presumed discrimination of children in drug treatment and drug development. The US Food and Drug Administration (FDA)-rewarded pediatric studies with antidepressants triggered in 2004 an FDA black-box warning of suicidality in young patients. Fewer antidepressants were prescribed, and the number of completed suicides of young persons increased. The dilemma between this warning and the need to adequately treat young depressed patients remains unsolved. We analyzed the history of drug development, the evolving view of diseases in young patients, US/EU pediatric laws, and pediatric studies triggered by FDA/European Medicines Agency (EMA) in depression and other diseases on the background of developmental pharmacology; financial, institutional, and other interests; and the literature. The FDA/EMA define children administratively, not physiologically, as <17 (FDA)/<18 years old (EMA). But young persons mature physiologically well before their 17th/18th birthday. Depression occurs in young persons, has special characteristics, but is not fundamentally different from adult depression. Young persons are not another species. Regulatory requirements for “pediatric” studies focus on “pediatric” labels. Many “pediatric” studies, including those in depression, lacked and lack medical sense and harm patients by placebo treatment although effective drugs exist. The FDA has partially abandoned separate “pediatric” efficacy studies, but not in psychiatry. Clinicians, parents, institutional review boards, and ethics committees should become aware of questionable “pediatric” studies, should re-evaluate ongoing ones, consider to suspend them, and to reject new ones. The concept of separate “pediatric” drug approval needs to be abandoned.

Highlights

In 2003, a warning by the British Committee on Safety of Medicines cautioned against the use of paroxetine in children and adolescents under the age of 18 years to treat depression,[1] after safety concerns had been reported by GlaxoSmithKline.[2]
The data that triggered these warnings came from 23 industry-sponsored pediatric antidepressant studies and the nationally funded United States (US) Treatment of Adolescents with Depression Study (TADS) that had investigated major depressive disorder (MDD), obsessive-compulsive disorder, and other psychiatric disorders
It took decades for the recognition that depression exists in young persons

Summary

Introduction

In 2003, a warning by the British Committee on Safety of Medicines cautioned against the use of paroxetine in children and adolescents under the age of 18 years to treat depression,[1] after safety concerns had been reported by GlaxoSmithKline.[2] Worldwide, regulatory authorities took up this warning in different ways.[3] The United States (US) Food and Drug Administration (FDA) issued a black-box warning that antidepressants increase the risk of suicidality in young patients.[2] The data that triggered these warnings came from 23 industry-sponsored pediatric antidepressant studies and the nationally funded US Treatment of Adolescents with Depression Study (TADS) that had investigated major depressive disorder (MDD), obsessive-compulsive disorder, and other psychiatric disorders These studies resulted in a committee of clinicians, convened by the FDA, to discuss the findings.[2] The black-box warning resulted in fewer prescriptions of antidepressants for young patients, less suicidality, but more completed suicides.[2,4] This issue has been controversial from the beginning. Some critical methodological comments were made,[3] most publications have in common that they do not challenge the basic approach of the pediatric studies in antidepressants.[14]

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Results

Conclusion