Pharmacogenomic Testing in Child and Adolescent Psychiatry: An Evidence-Based Review

Abstract

Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2A receptor genes (e.g., HT2AR) and catecholamine pathway genes (e.g., COMT) are reviewed. These commonly tested pharmacogenomic markers are discussed with regard to studies of drug levels, efficacy and side effects. The translation of pharmacogenomics to individualized/precision medicine in pediatric patients with ADHD, anxiety and depressive disorders has accelerated; however, its application remains challenging given that there are numerous divergent pathways between medication/medication dose and clinical response and side effects. Nonetheless, by leveraging variations in individual genes that may be relevant to medication metabolism or medication target engagement, pharmacogenomic testing may have a role in predicting treatment response, side effects and medication selection in youth with ADHD, depressive and anxiety disorders.

Clinical utility of pharmacogenetic testing in children and adolescents with severe mental disorders

“…This is in keeping with the recent literature suggesting the clinical utility of other pharmacogenetic tools such as Amplichip (Chau and Thomas 2015 ). Furthermore, two recent reviews, one of them focused on child psychiatry, suggest that even if the improvement in health outcomes and the cost-effectiveness of pharmacogenomics are not consistently replicated, PGx testing appears to be a promising tool that might help in predicting treatment response and adverse events (Rosenblat et al 2017 ; Wehry et al 2018 ).…”

“…In a recent systematic review of clinical trials and cost-effectiveness studies of PGx testing on the clinical outcome of MDD, the authors concluded that clear-cut demonstration of improved health outcomes and cost-effectiveness of pharmacogenomics were not yet supported with replicated evidence; however, they recognized that some studies have reported promising results for the clinical utility of PGx testing (Rosenblat et al 2017 ). In another review of PGx testing in child and adolescent psychiatry, the authors concluded that PGx testing might help in predicting treatment response and adverse events, as well as medication selection in children and adolescents with depressive disorders, anxiety disorders, and ADHD (Wehry et al 2018 ). Furthermore, in a case report using the Genecept assay testing (Genomind, Chalfont, PA, USA), the authors reported that PGx testing helped in prescribing the most effective medication, thus illustrating “how pharmacogenetics and psychiatry can potentially interface to provide more informed decision-making regarding use of psychotropic medications” (Smith et al 2015 ).…”

The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T are associated with antipsychotic safety parameters in adolescents with an acute psychotic episode: the results of a pilot study

“…Большинство работ, в которых изучалась фармакогенетика антипсихотиков у детей, проведены не на пациентах О Р И Г И Н А Л Ь Н Ы Е И С С Л Е Д О В А Н И Я И М Е Т О Д И К И [12], т. е. в этих исследованиях будут различаться и дозы, и сроки получения препаратов по сравнению с нашим. Учитывая малое число опубликованных работ, близких к нашей по дизайну, сравнение с другими педиатрическими выборками не представляется возможным.…”

“…К настоящему моменту проведено достаточно большое количество фармакогенетических исследований эффективности и безопасности антипсихотиков у детей и подростков, однако среди них недостаточно исследований, включающих больных с острым психотическим эпизодом [12]. Другие работы, подтверждающие значение CYP2D6 для безопасности антипсихотиков, преимущественно включают взрослых пациентов с шизофренией [13,14].…”

Pharmacogenetics biomarkers of antipsychotics’ safety in adolescents with acute psychotic episode

“…Проведенный анализ степени выраженности экстрапирамидных симптомов по специальным шкалам -BARS, SAS, and AIMS -не выявил зна-острым психотическим эпизодом [5]. Подавляющее большинство работ посвящены детям, принимающим антипсихотики в связи с расстройствами аутистического спектра [2,3,4] и по другим причинам [1]. Полиморфные варианты генов CYP2D6 и ABCB1 -наиболее вероятные кандидаты для фармакогенетических исследований безопасности антипсихотиков.…”