Nonresponse to high-dose bupropion for depression in a patient carrying CYP2B6 *6 and CYP2C19 *17 variants: a case report.

Publisher: Future Medicine Ltd Country of Publication: England NLM ID: 100897350 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-8042 (Electronic) Linking ISSN: 14622416 NLM ISO Abbreviation: Pharmacogenomics Subsets: MEDLINE

Publication: London : Future Medicine Ltd
Original Publication: London : Ashley Publications,

Antidepressive Agents, Second-Generation/*therapeutic use ; Bupropion/*therapeutic use ; Cytochrome P-450 CYP2B6/*genetics ; Cytochrome P-450 CYP2C19/*genetics ; Depressive Disorder/*drug therapy ; Depressive Disorder/*genetics; Adult ; Alleles ; Antidepressive Agents, Second-Generation/administration & dosage ; Bupropion/administration & dosage ; Cytochrome P-450 CYP2B6/metabolism ; Cytochrome P-450 CYP2C19/metabolism ; Genetic Variation ; Hospitalization ; Humans ; Male ; Pharmacogenetics ; Polymorphism, Single Nucleotide ; Recurrence ; Treatment Failure

We report the case of a patient with major depression treated with high-dose bupropion due to prior detected subtherapeutic blood concentrations at standard dosing. Pharmacogenetic panel testing identified the patient as a carrier of the CYP2B6 *6 allele, which has been associated with reduced bupropion metabolism and decreased concentrations of the pharmacologically active metabolite hydroxybupropion. Interestingly, we also found the patient to be homozygous for the CYP2C19 *17 allele, predicting an ultra rapid metabolizer phenotype. We propose a combined effect of the detected CYP2C19 and CYP2B6 genetic variants on bupropion metabolism. This case underlines the potential benefit of pre-emptive pharmacogenotyping but also the yet still fragmentary evidence making precise pharmacogenotype guided antidepressant selection and dosing challenging.

Keywords: CYP2B6; CYP2C19; CYP450; antidepressant; bupropion; depression; pharmacogenomics; psychiatry

0 (Antidepressive Agents, Second-Generation)
01ZG3TPX31 (Bupropion)
EC 1.14.14.1 (CYP2B6 protein, human)
EC 1.14.14.1 (CYP2C19 protein, human)
EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
EC 1.14.14.1 (Cytochrome P-450 CYP2C19)

Date Created: 20201030 Date Completed: 20210826 Latest Revision: 20210826

20240829

10.2217/pgs-2020-0087

33124517