Pharmacogenetic testing to guide therapy for children with mental health conditions

Psychoactive medications are increasingly used for the management of mental health conditions in children and youth. About 9% of young people (ages three-to-19 years) are receiving an antidepressant, antianxiety or antipsychotic medication in Canada, while an additional 3.6% receive psychostimulants for attention-deficit hyperactivity disorder. Pharmacogenetic (PGx) testing is one method being used to maximize treatment efficacy and prevent adverse drug reactions to psychoactive medications, by identifying specific gene variants that influence such outcomes. A new practice point from the Canadian Paediatric Society outlines the indications and principles underlying PGx testing and provides tables to guide and interpret PGx testing for psychoactive medications in children. The practice point does not recommend or endorse PGx testing for all children with mental health illnesses.Data based on PGx relevant to mental health are growing rapidly; however, the number of drug−gene associations for which the level of evidence is sufficient to include them in clinical PGx guidelines is still relatively small. The practice point document includes a table of established drug−gene associations for psychoactive medications, including antipsychotics, antidepressants, antiseizure medications and tetrabenazine, which is used for movement disorders. The table lists the name of the medication, the relevant gene, and sources for clinical guidance and/or inclusion in US/Canadian product labelling. As the expression of most drug metabolizing genes reaches adult values before one year of age, these guidelines can be used in children. Currently, PGx testing is strongly recommended or required before starting a child or youth on the antiseizure medications carbamazepine or valproic acid (< 2 years of age), or tetrabenazine.For some psychoactive medications, drug−gene associations are too weak to guide clinical practice; therefore, no treatment adjustments based on PGx variant status are proposed or required. Separate tables in the practice point document list drug−gene interactions without clinical implications and those with insufficient evidence for use in clinical practice. Many commercial companies offer PGx testing, with prices ranging from $200–$400. Testing is mostly conducted using buccal swabs. Companies have different test panels, and many target several mental health conditions by including a large number of genes (sometimes > 100), most of which are not included in clinical practice guidelines. Many companies also work with laboratories based in the US, which has raised privacy concerns. The Canadian Paediatric Society practice point document stresses that physicians should never rely on PGx test results that are not reflected in current guidelines. In addition, PGx information alone will not identify a preferred medication but may exclude treatment options. The choice of medication should always be based on a full clinical picture.Families often arrange for PGx testing themselves and bring the results to their healthcare provider appointment. To help patients and families understand the value of PGx test results, healthcare providers must be able to answer four questions:Is testing conducted for a drug−gene association covered by a clinical PGx guideline? (Tables 2, 3 and 4 in the practice point document can be used to answer this question.) Is this child or youth’s current treatment being affected by PGx test results? Ongoing treatment with a psychoactive medication that is well-tolerated and effective usually does not require further intervention based on PGx test results. However, a child’s metabolizer status may help explain an adverse drug reaction or a treatment that has failed. The full clinical picture should be considered when determining whether a dose adjustment or alternative treatment suggested by PGx results is indicated.Can PGx testing guide future care for this child or youth? PGx test results alone cannot identify what treatment is best, but can help inform decisions about medications to avoid, or help with optimization of dose.Are non-psychoactive medications this child or youth is taking being affected by the PGx results? PGx test results can sometimes provide guidance for medications unrelated to mental health. The practice point document concludes that PGx testing is a promising method of providing safer, more effective and individualized medication choices for children and youth with mental health conditions. Testing is currently recommended for carbamazepine, valproic acid (in children < 2 years of age) and tetrabenazine, but not all provincial/territorial health plans cover costs. Physicians are increasingly presented with PGx test results, but must realize that current evidence is sufficient for only a select few drug−gene associations in children. Knowing when to initiate testing, interpret or reject test results, and consult with experts in the field for guidance are becoming key components of quality mental health care for children and youth.Reference1. Verstegen RHJ, Cohn I, Feldman ME, et al; Canadian Paediatric Society, Drug Therapy Committee. Gene-based drug therapy for children and youth treated with psychoactive medications. (accessed March 7, 2024).

Pharmacogenetic testing to guide therapy for children with mental health conditions

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