Pharmacogenetic CYP2D6 variability, phenoconversion and treatment outcomes: A Danish population-based cohort study in 6, 798 individuals initiating atomoxetine treatment. (1st June 2022)

• Record Type: Journal Article
• Authors: Ishtiak-Ahmed, K.; Lunenburg, C.; Thirstrup, J.; Clausen, L.; Thomsen, P.; Gasse, C.
• Is Part Of: European psychiatry. Volume 65:Supplement 1(2022)
• Page Start: S227
• Page End: S227
• Publication Date: 2022-06-01
• Subjects: treatment switching -- CYP2D6 inhibitors -- adhd -- sleeping problem; Psychiatry -- Periodicals; Mental illness -- Periodicals; Electronic journals; 616.89
• DOI: 10.1192/j.eurpsy.2022.588
• Languages: English
• ISSNs: 0924-9338

Abstract

Abstract : Introduction: Atomoxetine, a first-line treatment option for ADHD, is affected by pharmacogenetic (PGx) variation of the drug-metabolizing enzyme CYP2D6. Despite the recommendation of CYP2D6 testing, the use of PGx-guided dosing remains low in Denmark. Objectives: We investigated wide-ranging clinical outcomes in atomoxetine users in association with PGx variability. Methods: We analyzed 6, 798 individuals (55% children) with a first prescription for atomoxetine identified from the Danish population-based iPSYCH case-cohort study linking biobank information with Danish registers. Individuals were categorized based on their single-nucleotide-polymorphism-based CYP2D6 genotype into normal (NM), intermediate (IM), and poor metabolizer (PM). Clinical outcomes included treatment switching, discontinuation, psychiatric inpatient-, outpatient-, and emergency contact, suicide attempt/self-harm, sleep problem, and depression. Individuals' CYP2D6-status could change due to drug-drug-interactions of weak, intermediate, or strong-CYP2D6 inhibitors (phenoconversion), which we accounted for by time-varying phenotype assessment. Incidence rate ratios (IRR) were estimated using Poisson regression analyses and adjusted for a wide range of potential confounders and covariates. Results: Over two-thirds of the individuals had a hospital diagnosis of ADHD at the first atomoxetine prescription. The distribution of CYP2D6 phenotypes was similar in children and adults. IM/PM children had a significantly higher risk of a sleeping problem compared with NM children (IRR 1.25, 95% CI 1.01-1.54). Compared with NM adults, those with IM/PM had a higher risk of switching (1.15, 95% CI 0.98-1.35). Conclusions: This is the first study showing the potential impact of PGx variability on clinical outcomes of atomoxetine users in a population-based setting, highlighting the utility of PGx testing. Disclosure: No significant relationships.