Commercial Pharmacogenetic Tests in Psychiatry: Do they Facilitate the Implementation of Pharmacogenetic Dosing Guidelines?

Abstract

Introduction Expert groups have created dosing guidelines to facilitate the implementation of pharmacogenetic knowledge into clinical practice and commercial pharmacogenetic tests are becoming increasingly accessible. However, the extent to which these commercial tests facilitate the implementation of dosing guidelines is not clear. Methods Gene-drug pairs included on 22 commercial pharmacogenetic test panels were extracted and cross-referenced with the 74 gene-drug pairs with dosing guidelines in the Pharmacogenetics Knowledgebase, with particular attention given to the 28 gene-drug pairs relevant to psychiatry. Results On average, 70% of the 28 gene-drug pairs most relevant to psychiatry were covered by the examined tests. Six gene-drug pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline, CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline) were included by all tests. Gene-drug pairs included on less than half of the test panels included HLA-B-phenytoin (14%), HLA-A-carbamazepine (24%), HLA-B-carbamazepine (29%), and CYP2D6-zuclopenthixol (43%). Discussion Most commercial pharmacogenetic tests we examined are well-equipped to facilitate implementation of the majority of dosing guidelines relevant to psychiatry but are limited in their ability to facilitate implementation of the full spectrum of dosing guidelines currently available.

Clinical Utilization of Pharmacogenetics in Psychiatry – Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry

“…Education for clinicians, patients, and family members is crucial to implementation. PGx testing serves as a shared decision support tool that facilitates the implementation of PGx guidelines into clinical practice and improves outcomes for patients receiving psychopharmacological treatments, including those with MDD [15].…”

“…Clinical practice guidelines are one way to increase universal incorporation of recommended medical management practices into standard of care. The availability of guidance and clinical practice guidelines from the FDA (package inserts), the CPIC, the Dutch Pharmacogenetic Working Group dosing guidelines, and the Canadian Pharmacogenomics Network for Drug Safety can help facilitate PGx testing into real world clinical practice, but further clinical practice guidelines by professional medical organizations around how to evaluate and utilize a PGx test may be helpful for practical usage of the tests (▶Tables 1 and 2) [15,26,27,73]. The International Society of Psychiatric Genetics recommends that "when pharmacogenetic testing results are already available, clinicians are encouraged to integrate this information into their medication selection and dosing decisions" [74].…”

“…While some psychotropic medications are metabolized by other CYP enzymes, most of the existing PGx information concentrates on CYP2D6 and CYP2C19 owing to their high degree of genetic variation and significant role in the metabolism of TCAs, SSRIs, and antipsychotics (▶Table 2) [14]. These guidelines and actionable PGx information within product labeling have facilitated the clinical implementation of PGx in psychiatry; however, guidance on when the test should be obtained is still lacking [15].…”

From the Origins of Pharmacogenetics to First Applications in Psychiatry

“…Implementation of pharmacogenetic testing is spreading in medical centers that have started to routinely provide pharmacogenetic testing for psychiatric patients [44,45]. Also, despite their lack of standardization by regulatory agencies and lack of gene-specific recommendations, commercial tests have become available to the public, including tests that are restricted to be ordered by physicians [46,47].…”

Pharmacogenetics in Psychiatry

“…Fan & Bousman [3] investigated in their article whether commercial pharmacogenetic testing kits are useful to facilitate implementation of medication dosing guidelines. The authors reviewed 22 commercial test panels and noted that six gene-drug pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline, CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline) were included by all tests.…”