Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients

Öz, Merve Demirbugen; Başkak, Bora; Uçkun, Zuhal; Artun, Nazan Yuce; Özdemir, Hatice; Ozel, Tugba Kizil; Özgüven, Halise Devrimci; Süzen, Sinan

doi:10.1038/s41397-019-0127-8

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…Furthermore, carriers of the ABCB1 variants rs2235015, rs2235040, rs2032582 and rs1128503 that are in high-linkage disequilibrium with rs2032583 needed lower antidepressant doses to reach remission of depression in clinical trials testing a none fixed-dose regimen and showed a greater likelihood of intolerance to antidepressants [84]. The rs1128503 has been furthermore associated with a higher likelihood of SSRI side effects, in other words, sexual dysfunction [85].…”

Section: Tricyclic Antidepressantsmentioning

confidence: 99%

Therapy Response Prediction in Major Depressive Disorder: Current and Novel Genomic Markers Influencing Pharmacokinetics and Pharmacodynamics

et al. 2021

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Major depressive disorder is connected with high rates of functional disability and mortality. About a third of the patients are at risk of therapy failure. Several pharmacogenetic markers especially located in CYP450 genes such as CYP2D6 or CYP2C19 are of relevance for therapy outcome prediction in major depressive disorder but a further optimization of predictive tools is warranted. The article summarizes the current knowledge on pharmacogenetic variants, therapy effects and side effects of important antidepressive therapeutics, and sheds light on new methodological approaches for therapy response estimation based on genetic markers with relevance for pharmacokinetics, pharmacodynamics and disease pathology identified in genome-wide association study analyses, highlighting polygenic risk score analysis as a tool for further optimization of individualized therapy outcome prediction.

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Section: Tricyclic Antidepressantsmentioning

confidence: 99%

Therapy Response Prediction in Major Depressive Disorder: Current and Novel Genomic Markers Influencing Pharmacokinetics and Pharmacodynamics

et al. 2021

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“…PGx data are available to suggest a relationship between transporter pharmacogenetics and patient propensity for adverse effects associated with SSRI use. Preliminary studies suggest that the “S” allele of SLC6A4 is associated with an increased risk of insomnia and agitation, whereas the “L” allele is associated with sexual dysfunctions [ 46 , 47 ]. An association between the HTR2A rs6311 T/T genotype and the development of sexual dysfunction is seen in patients being treated for major depressive disorder [ 47 ].…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Sandritter,

Chevalier,

Abt

et al. 2023

Pharmaceuticals

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Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5.

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“…[2][3][4] Further, SSRIs have also been shown to activate 5-HT 2A and 5-HT 2C receptors inhibiting dopaminergic and adrenergic pathways that facilitate sexual motivation and behaviours. [5][6][7] The rates of sexual dysfunction associated with SSRI treatment have been reported to be between ∼25% and ∼80%, with the lower cited rates more likely a function of underreporting by patients in trials that did not specifically assess these side effects. 3,[8][9][10][11] There is also considerable variation in the type and intensity of sexual side effects experienced between patients on SSRIs.…”

Section: Introductionmentioning

confidence: 99%

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study

Islam,

Magarbeh,

Elsheikh

et al. 2023

Can J Psychiatry

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Objectives Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6, and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample. Methods A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0–8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n = 91), while responders continued ESC (i.e., ESC-Only, n = 80) from weeks 8–16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0–8 and 8–16, using repeated measures mixed-effects models. Results In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8–16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F(2,54) = 8.00, p < 0.001, q = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF ( r = −0.42, p = 0.004, q = 0.034) and SS ( r = −0.43, p = 0.003, q = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction ( r = −0.39, p = 0.009, q = 0.052). Conclusions CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

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Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients

Cited by 15 publications

References 33 publications

Therapy Response Prediction in Major Depressive Disorder: Current and Novel Genomic Markers Influencing Pharmacokinetics and Pharmacodynamics

Therapy Response Prediction in Major Depressive Disorder: Current and Novel Genomic Markers Influencing Pharmacokinetics and Pharmacodynamics

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study

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