Understanding the pharmacogenetics of selective serotonin reuptake inhibitors

  title={Understanding the pharmacogenetics of selective serotonin reuptake inhibitors},
  author={Chiara Fabbri and Alessandro Minarini and Tomihisa Niitsu and Alessandro Serretti},
  journal={Expert Opinion on Drug Metabolism \& Toxicology},
  pages={1093 - 1118}
Introduction: The genetic background of antidepressant response represents a unique opportunity to identify biological markers of treatment outcome. Encouraging results alternating with inconsistent findings made antidepressant pharmacogenetics a stimulating but often discouraging field that requires careful discussion about cumulative evidence and methodological issues. Areas covered: The present review discusses both known and less replicated genes that have been implicated in selective… 

Pharmacogenetics of Major Depressive Disorder: Top Genes and Pathways Toward Clinical Applications

The cumulative evidence supports the involvement of some genes and molecular pathways in antidepressant efficacy and the relevance of SLC6A4, HTR2A, ABCB1, and cytochrome P450 genes.

Effect of Cytochrome P450 polymorphism on the action and metabolism of selective serotonin reuptake inhibitors

The implementation of a stratified approach to medication with SSRIs in different metabolic phenotypes on a rational basis will require new studies assessing the association between clinical outcomes (such as adverse reactions) and genetically determined elevated plasma concentrations.

TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics

Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.

Effect of Serotonin Transporter 5-HTTLPR Polymorphism on Gastrointestinal Intolerance to Metformin: A GoDARTS Study

The results indicate that the interaction between OCT1 and SERT genes might play an important role in metformin intolerance, and further studies are needed to substantiate the hypothesis that meetformin gastrointestinal side effects could be related to the reduced intestinal serotonin uptake.

Prenatal exposure to serotonin reuptake inhibitors and congenital heart anomalies: an exploratory pharmacogenetics study.

The role of pharmacogenetics in determining the risk of congenital heart anomalies with prenatal use of serotonin reuptake inhibitors is studied to identify several polymorphisms that might potentially affect therisk of CHA among exposed fetuses.

Possibilities and limitations of antidepressant use to correct depressive and negative symptoms in schizophrenia

The review suggests that antidepressants (ADs) are effective medications and they can be prescribed to correct depressive disorders and negative symptoms in patients with schizophrenia when used in combination with antipsychotics (АPs), however, when administering ADs and АPs combinations, it is important to consider the safety profile of these combinations as well as their tolerance.

Targeting drug sensitivity predictors: New potential strategies to improve pharmacotherapy of human brain disorders

Early adoption of pharmacogenetic testing for veterans prescribed psychotropic medications.

Most prescribing decisions were congruent with test results, but in a nontrivial number of cases, prescribers appeared not to act on the results.

Paving ways for personalizing drug therapy during pregnancy : A focus on the risk of drug teratogenicity

Signs are found for a role of genetic differences in the body’s reaction to SRIs and the development of heart defects among children whose mothers had used SRIs during the first trimester of pregnancy and on the use of serotonin reuptake inhibitors, a group of antidepressants, and the risk ofheart defects.



Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response

The findings suggest that novel genetic markers in the COMT distal promoter may influence SSRI response phenotypes.

Pharmacogenetics of antidepressant medication intolerance.

Pharmacodynamic differences among patients due to variant 5-HT(2A) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance and pharmacogenetic markers may be useful in predicting antidepressant treatment outcome.

Investigation of serotonin-related genes in antidepressant response

Results implicate TPH1 and SLC6A4 in general response, and HTR2A, TPH2, and MAOA in the specificity of response to fluoxetine, and a number of the less frequent alleles of many of the SNP markers were associated with the nonresponse and nonspecific phenotypes.

Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response

It appears that genetic variation in these five genes has a marginal effect on response to citalopram, although a previously observed association was supported and awaits replication in an independent sample.

Pharmacogenomics of antidepressant induced mania: a review and meta-analysis of the serotonin transporter gene (5HTTLPR) association.

FKBP5 genetic variation: association with selective serotonin reuptake inhibitor treatment outcomes in major depressive disorder

A comprehensive FKBP5 sequence study provides insight into the role of common genetic polymorphisms that might influence SSRI treatment outcomes in major depressive disorder patients.

Genetic polymorphisms of cytochrome P450 enzymes and antidepressant metabolism

The authors aim to give an overview of the published studies analyzing the influence of CYP highly polymorphic loci on antidepressant treatment in order to translate the acquired knowledge to a clinical level.

Genetic predictors of response to antidepressants in the GENDEP project

The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response to the serotonin-reuptake-inhibiting escitalopram, genes encode proteins in norepinephrine signaling influencingresponse to the norpinephrine-reptake- inhibiting nortriptyline and a common pathway gene influencing response in response to both antidepressants.

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy