title: Psychiatric diseases moving towards adolescents and children: How much room is there for extrapolation?
abstract: Since medicines for psychiatric diseases are often studied in adults first, it would be useful if data from efficacy trials in adults could be extrapolated to children and adolescents. However, it is not sufficient to adapt the adult dosages to achieve systemic exposure levels similar to those effective in adults. This can be done with increasing predictive accuracy but before accepting that the same plasma levels should result in the same efficacy as in adults both the mechanism of action of the drug and the pathophysiology of the disease must be considered. For psychiatric disorders there is often insufficient evidence to support the assumptions for extrapolating efficacy as it is not even always sure that the same diagnostic categories correspond to the same disease in adults and children. Even when the basic biological alteration behind the disorder could be considered the same, the psychodynamic consequences and the role of non-pharmacological approaches to treatment may substantially differ across age groups. These facts, together with the absence of detailed historical data on the actual correlations between paediatric and adult responses for many types of psycho-therapeutic medicines, make it difficult to accept extrapolation as the main proof of efficacy in children and adolescents. A corollary is that since efficacy studies will normally be required, they should not be unduly postponed. For products addressing a medical need with good scientific plausibility, they should be initiated as soon as the anticipated safety concerns can be reasonably managed within the context of a paediatric clinical trial.
authors: Department of Pharmacology, Universidad Complutense de Madrid, Madrid, Spain. Electronic address: fandrest@med.ucm.es.
authors: F
authors: F
authors: de Andres-Trelles
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002665:Child Psychiatry; D055808:Drug Discovery; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents
keywords: Adolescent psychiatry; Child psychiatry; Efficacy clinical trials; Extrapolation; Paediatrc drug development; Psychopharmacology