Using these resources, Bousman and colleagues1 summarized the current gene-drug interaction information and proposed a minimum testing panel that can serve as a primer for clinical implementation. A total of 448 gene-drug interactions were identified in psychiatry: only 31 (7%) of them satisfied the criteria for the highest level of evidence from PharmGKB (level 1A or 1B), drug labels (testing recommended or required), and clinical guidelines (Clinical Pharmacogenetics Implementation Consortium [CPIC] or Royal Dutch Association for the Advancement of Pharmacy-Pharmacogenetics Working Group [DPWG]). Among those, with the highest level of evidence, 59% involved the CYP2D6/CYP2C19 genes and antidepressant medications (eg, SSRIs and tricyclic antidepressants).
Several gene-drug interactions with high-level evidence were identified between 2 human leukocyte antigen genes (HLA-A and HLA-B) and three anticonvulsants and/or mood stabilizers (carbamazepine, oxcarbazepine, and phenytoin). High-level evidence interactions involving the CYP2C9 and POLG genes were reported to phenytoin and valproic acid, respectively. Regarding antipsychotics, the following five gene-drug interactions satisfied the criteria for the highest level of evidence: CYP2D6 and aripiprazole, haloperidol, pimozide, risperidone, and zuclopenthixol.
Based on the gene-drug interaction evidence, a minimum PGx testing panel for psychiatry was proposed, in which 16 variant alleles within the CYP2C9, CYP2C19, CYP2D6, HLA-A, and HLA-B genes were included.
This proposed panel is clinically relevant; however, readers should consider certain limitations, including:
1) The proposed panel does not address gene-gene interactions.
2) The proposed minimum panel requires regular updates in line with PGx resource updates (eg, CPIC).
3) PGx testing should be used as a support tool, along with other information (eg, age, sex, ethnicity, and concomitant medications), and should be applied in line with other clinical treatment guidelines. While recommendations exist on how to use pharmacokinetics variants for some antipsychotics, no pharmacodynamics gene variants for antipsychotics have been proposed for clinical practice to date.
A number of commercial PGx testing tools including pharmacodynamics gene variants are being offered by several commercial companies for use in clinical practice. A recent survey evaluated physicians’ opinions of PGx testing and their experiences using such tests for prescribing psychotropics through the The Individualized Medicine: Pharmacogenetic Assessment and Clinical Treatment (IMPACT) study.2 Of the 168 clinicians surveyed, 80% believed that PGx testing will become a common standard in psychiatric drug treatment; moreover, these responders were satisfied or very satisfied with the genetic information provided. These findings indicate the feasibility and suggested clinical utility of PGx testing.
In several studies, including randomized controlled trials, the clinical utility of PGx testing for antidepressants has been investigated. A recent meta-analysis included four randomized controlled trials and two open-label controlled cohort studies.3 The findings indicate that treatment guided by PGx testing, including combinatorial testing, is superior to treatment as usual in response and/or remission rates in the acute treatment of depression.
However, further investigation focusing on the clinical validity and efficacy of single and combinatorial PGx testing for antipsychotic treatment responses is warranted. Currently, some randomized controlled trials evaluating the clinical utility of PGx testing on antipsychotics in patients with schizophrenia are underway (eg, NCT02573168 and NCT02566057), which should contribute to important advances in this field.
Dr Yoshida is a Postdoctoral Research Fellow, Centre for Addiction and Mental Health, Toronto, ON, Canada, and a Psychiatrist, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Dr Müller is Head, Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, and Professor, Department of Psychiatry, University of Toronto, ON. The authors report no conflicts of interest concerning the subject matter of this article.
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