Pharmacogenomics Data Analyst The Hospital for Sick Children Toronto, Ontario, Canada
Background: Pharmacogenetic (PGx) testing, a pillar of precision medicine, can identify individuals who may benefit from non-standard medication dosing or selection of alternate therapies. The International Society of Psychiatric Genetics recommends PGx testing for antidepressants and antipsychotics, among other medications. Despite this, uptake of PGx testing in mental health settings has been hindered by limited evidence for certain gene-drug combinations, access to testing, and concerns of uncertain clinical utility. Objective: Evaluate the perceived utility and clinical actionability of PGx testing in a cohort of pediatric patients with diverse psychiatric indications. Design/Methods: The cohort comprised 70 pediatric patients with various psychiatric conditions, including mood, anxiety, and neurodevelopmental disorders. Patients underwent PGx panel testing of 9 genes with available published PGx-dosing guidelines. Electronic health records were reviewed to capture medication history. Analyses focused on CYP2D6 and CYP2C19, which are involved in the breakdown of various psychoactive medications. PGx testing was actionable if the results explained the referral concern, such as adverse drug reaction (ADR) or lack of efficacy. Perceived utility of PGx testing was evaluated by surveying 28 referring healthcare providers (HCPs). Results: 52 patients had a history of ADR and/or inefficacy related to at least one psychoactive medication with associated PGx-dosing guidance [median: 2, range: 2-5]; sertraline being the most frequent (56% of patients). 38 patients had an ADR, of which 3 (8%) had genotypes supporting a dose reduction or selection of alternate therapy. Of the 20 patients with reported limited therapeutic effect, 2 (10%) would have benefited from an increased dose or selection of alternate therapy. The utility survey was completed by 13 HCPs (response rate 46%). Generally, HCPs expressed that PGx testing was relevant for their patient(s) at the time of testing. Notably, 8 (62%) HCPs indicated they were uncertain about recommending PGx testing as standard of care for their patient population.
Conclusion(s): For drug classes with established PGx guidelines such as selective serotonin reuptake inhibitors, PGx testing may be a useful tool if applied preemptively to inform dosing decisions. However, the proportion of patients whose non-response or ADR could be attributed to PGx variation was relatively low. These findings highlight the potential influence of other physiological mechanisms on psychoactive medication response that warrant further investigation.
