Off-Label Prescription of Antidepressants to Minors

The general question, if antidepressants should be prescribed to minors, is already a controversial issue in psychiatry. If possible, psychotherapeutic treatments are favoured over (solely) pharmacological ones. 

In cases where antidepressants are administered to minors these tend to be off-label. In Germany and the USA, 36-55% of all such drugs are prescribed to minors off-label. In contrast, only few drugs are authorised for treating minors affected by depression. In the United States, for example, only two drugs have been authorised for the treatment of major depression in minors. In Germany, only the selective serotonin reuptake inhibitor and active substance “Fluoxetine” is authorised since 2006 for children from age of 8 onwards. The off-label prescription of anti-depressants that are at present solely authorised for adults results in an often insufficient amount of evidence for their efficacy and tolerance in minors.

Borchard-Tuch, Claudia (2008): Depression. Wenn Kindern nichts mehr Freude macht. In: Pharmazeutische Zeitung 153(16).

Kölch, Michael /Fegert, Jörg M. (2007): Medikamentöse Therapie der Depression bei Kindern und Jugendlichen. In: Praxis der Kinderpsychologie und Kinderpsychiatrie 56(3), 224-233. Online Version

Mayo Foundation for Medical Education and Research (27. Mai 2016): Antidepressants for children and teens. Online Version

The issue surrounding the tolerance of off-label prescriptions manifests itself especially when considering previously unknown, major side-effects of drugs in minors. In 2007, the US Food and Drug Administration required a black box warning on labels of Serotonin reuptake inhibitors (SSRI), which pointed to the risk of an increase in suicidality in minors connected with the intake of such drugs. This decision was a reaction to a meta-study conducted the same year by Cipriani et al., which analysed the use of antidepressants among minors from 1988 to 2006. It followed from its results that the use of antidepressants in minors could cause or reinforce suicidal thoughts.

Background information for the decision of the US Food and Drug Administration: Online Version

Cipriani, Andrea / Zhou, Xinyu / Del Giovane, Cinzia / Hetrick, Sarah E. / Qin, Bin / Whittington, Craig / Coghill, David / Zhang, Yuqing / Hazell, Philip / Leucht, Stefan / Cuijpers, Pim / Pu, Juncai / Yang, David / Lui, Lanxiang / Xie, Peng (2016): Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. In: The Lancet 388(10047), 881–890. Online Version

Holtmann, Martin / Bölte, Sven / Poustka, Fritz (2006): Suizidalität bei depressiven Kindern und Jugendlichen unter Behandlung mit selektiven Serotoninwiederaufnahmehemmern. In: Der Nervenarzt 77(11), 1332-1337. Online Version

Following studies relativise the risk of suicidality while also shedding light on the lack of evidence for the efficacy of numerous antidepressants in minors. In fact, only the efficacy of the aforementioned Fluoxetine for the treatment of depression in minors has been backed with sufficient evidence. In addition, the drug has not exhibited an increased danger of fuelling the development of suicidal intentions or thoughts in minors. Kölch and Fegert conclude that there is, thus, only one evidence-backed pharmacotherapeutic option for depressive minors which shall be framed by security measures and accompanied by psychiatric treatment.

Furthermore, the publications of Cipriani et al., Jureidini et al., as well as Bridge et al. illustrate that in some studies that tested the tolerability of anti-depressants in minors the quality of research was insufficient. Weaknesses like the non-publication of negative results as well as the insufficient specification of indicators for an increased suicidality have been discovered.

Bridge, Jeffrey A. / Iyengar, Satish / Salary, Cheryl B. /Barbe, Rémy / Birmaher, Boris / Pincus, Harold Alan / Ren, Lulu / Brent, David A. (2007): Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. In: Journal of the American Medical Association 297(15), 1683-1696. Online Version

Jureidini, Jon N. / Doecke, Christopher J. / Mansfield, Peter R. / Haby, Michelle M. / Menkes, David B. / Tonkin, Anne L. (2004): Efficacy and safety of antidepressants for children and adolescents. In: British Medical Journal 328, 879–883. Online Version

Fegert, Jörg M. (2007): Development Psychopharmacology. In: Merkel, Reinhard / Boer, Gerard / Fegert, Jörg M. / Galert, Thorsten / Hartmann, Dirk / Nuttin, Bart / Rosahl, Steffen K.: Intervening in the Brain. Changing Psyche and Society, Berlin u.a.: Springer (Ethics of Science and Technology Assessment 29), 24-30. 

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