Case report: Non-response to fluoxetine in a homozygous 5-HTTLPR S-allele carrier of the serotonin transporter gene.

Autor:	Stäuble CK; Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.; Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.; Institute of Hospital Pharmacy, Solothurner Spitäler AG, Olten, Switzerland., Meier R; Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Lampert ML; Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.; Institute of Hospital Pharmacy, Solothurner Spitäler AG, Olten, Switzerland., Mikoteit T; Psychiatric Services Solothurn, Solothurner Spitälerler AG and Faculty of Medicine, University of Basel, Solothurn, Switzerland., Hatzinger M; Psychiatric Services Solothurn, Solothurner Spitälerler AG and Faculty of Medicine, University of Basel, Solothurn, Switzerland., Allemann SS; Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Hersberger KE; Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Meyer Zu Schwabedissen HE; Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in psychiatry [Front Psychiatry] 2022 Jul 15; Vol. 13, pp. 942268. Date of Electronic Publication: 2022 Jul 15 (Print Publication: 2022).
DOI:	10.3389/fpsyt.2022.942268
Abstrakt:	We report the case of a 50-year-old male with major depressive disorder (MDD) to illustrate the challenge of finding effective antidepressant pharmacotherapy and the role that the patient's genetic makeup may play. Recent treatment attempts before clinic admission included venlafaxine and fluoxetine. Venlafaxine was discontinued due to lack of response, and subsequently switched to fluoxetine based on pharmacogenotyping of the P-glycoprotein transporter (P-gp, encoded by ABCB1 ) by the outpatient psychiatrist. Despite steady state serum levels within the therapeutic range, the patient did not benefit from fluoxetine either, necessitating admission to our clinic. Here a clinical pharmacist-led medication review including additional pharmacogenetic (PGx) analysis resulted in the change of the antidepressant therapy to bupropion. Under the new regimen, established in the in-patient-setting, the patient remitted. However, based on the assessed pharmacokinetics-related gene variants, including CYP s and ABCB1 , non-response to fluoxetine could not be conclusively explained. Therefore, we retrospectively selected the serotonin transporter (SERT1, encoded by SLC6A4 ) for further genetic analysis of pharmacodynamic variability. The patient presented to be a homozygous carrier of the short allele variant in the 5-HTTLPR (S/S) located within the SLC6A4 promoter region, which has been associated with a reduced expression of the SERT1. This case points out the potential relevance of panel PGx testing considering polymorphisms in genes of pharmacokinetic as well as pharmacodynamic relevance. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Stäuble, Meier, Lampert, Mikoteit, Hatzinger, Allemann, Hersberger and Meyer zu Schwabedissen.)
Databáze:	MEDLINE
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