Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.

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Joas, ErikGothenburg University,Göteborgs universitet,Extern,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,External,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry (author)

Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.

Article/chapterEnglish2023

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2022-11-04
Springer Science and Business Media LLC,2023

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LIBRIS-ID:oai:gup.ub.gu.se/319748
https://gup.ub.gu.se/publication/319748URI
https://doi.org/10.1038/s41397-022-00294-4DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:151119677URI

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Language:English

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Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005-2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR]=1.3, 95% CI=1.04-1.62, p=0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR=1.46, 95% CI=1.05-2.02, p=0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.

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Jonsson, Lina,1982Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xjliny (author)
Viktorin, Alexander (author)
Smedler, ErikGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xsmeer (author)
Pålsson, ErikGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry (author)
Goodwin, Guy M (author)
Landén, Mikael,1966Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt (author)
Göteborgs universitetExtern (creator_code:org_t)

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In:The pharmacogenomics journal: Springer Science and Business Media LLC23:1, s. 28-351473-11501470-269X

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Psychiatry

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