Case report
Non-response to fluoxetine in a homozygous 5-HTTLPR S-allele carrier of the serotonin transporter gene
Bibliographic Data
| ID | 15529254 |
|---|---|
| Authors | Céline K Stäuble (0000-0002-2437-4803, Solothurner Spitäler, corresponding author), Rebecca Meier, Markus L Lampert (0000-0001-7037-2799, University of Basel), Thorsten Mikoteit (0000-0003-2166-6330, Solothurner Spitäler), Martin Hatzinger (0000-0002-6146-3602, Solothurner Spitäler), Samuel Allemann (0000-0003-4067-9401, University of Basel), Samuel S Allemann, Kurt E Hersberger (0000-0001-8678-697X, University of Basel), Henriette E Meyer zu Schwabedissen (0000-0003-0458-4579, University of Basel) |
| Year | 2022 |
| Volume | 13 |
| Pages | 942268-942268 |
| Publication date | 2022-07-15 |
| Open Access | Yes |
| Type | ARTICLE |
| Venue | Frontiers in Psychiatry (JOURNAL) |
| Journal identifiers | ISSN: 1664-0640 • E-ISSN: 1664-0640 |
| Publisher | Frontiers Media (PUBLISHER • CH) |
| DOI | 10.3389/fpsyt.2022.942268 |
| PMID | 35911243 |
| OpenAlex | W4285591267 |
| Language | EN |
| References cited | 38 |
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
5-HTTLPR · Allele · Biology · Fluoxetine · Gene · Genotype · Psychiatry · Serotonin · Serotonin Plasma Membrane Transport Proteins · Serotonin transporter · Transporter · Medicine · Neurotransmitter Receptor Influence on Behavior · Psychology · Treatment of Major Depression · Tryptophan and brain disorders · Genetics
Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D
The Economic Burden of Depression in the United States
Influence of Life Stress on Depression
Global, regional, and national disability-adjusted life-years (Dalys) for 359 diseases and injuries and healthy life expectancy (Hale) for 195 countries and territories, 1990–2017
Assessment of Depression
A Rating Scale for Depression
| Highly cited | No |
|---|