Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study

Menu, Patrick; Gressier, Florence; Verstuyft, Céline; Hardy, Patrick; Becquemont, Laurent

doi:10.1159/000319361

Cited by 32 publications

(23 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, various studies aimed at replicating this pharmacogenetic association with mixed results. A considerable body of research corroborated the finding by Uhr et al [] [Gex‐Fabry et al, ; Kato et al, ; Nikisch et al, ; Sarginson et al, ; Lin et al, ; Singh et al, ; Huang et al, ], but there were also a number of studies that failed to find a predictive value of ABCB1 polymorphisms on therapy outcome [Peters et al, ; Mihaljevic Peles et al, ; Menu et al, ; Perlis et al, ; Uher et al, ; GENDEP Investigators, MARS Investigators, and SI, ]. The possible reasons for these contradictory results are diverse and coincide with a generally observed difficulty in the replication of pharmacogenetic associations caused by, for example, heterogeneity of study designs and patient samples, variability in phenotype definitions (MD being a particularly heterogeneous phenotype), inadequate statistical power, environmental factors, and polymorphic heterogeneity, making it difficult to compare results across studies.…”

Section: Introductionmentioning

confidence: 66%

“…Association results from Roberts et al [], Gex‐Fabry et al [], Kato et al [], Mihaljevic Peles et al [], Nikisch et al [], Uhr et al [], Menu et al [], Sarginson et al [], Lin et al [], Singh et al [], and the STAR*D sample were combined in the meta‐analysis with a total of 1,845 patients (see Table ). We found no significant association between rs1045642 and P‐gp substrate treatment outcome, neither in the overall meta‐analysis nor after stratification for ethnicity, in‐/outpatient status or co‐medication.…”

Section: Resultsmentioning

confidence: 99%

“…If P ‐values or direction of association were not named explicitly in the paper, authors were contacted and asked for more detailed information. This was successful for all but three studies [Nikisch et al, ; Menu et al, ; Sarginson et al, ]; for these studies, Z‐values of 0 were used in the meta‐analysis. Z‐based meta‐analysis was performed using Stouffer's method [Stouffer et al, 1949], that is, association P ‐values were transformed into corresponding Z‐values.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

Breitenstein

Brückl

Ising

et al. 2015

American J of Med Genetics Pt B

View full text Add to dashboard Cite

The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene, plays a pivotal role in the transfer of various molecules across the blood-brain barrier. P-gp protects the brain by selectively extruding its substrates, including certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr et al. [2008] first showed that ABCB1 variants predicted the remission to antidepressants with P-gp substrate properties in patients suffering from major depression (MD). Other studies investigating the influence of ABCB1 polymorphisms on antidepressant treatment response produced inconclusive results. In this meta-analysis, we systematically summarized 16 pharmacogenetic studies focused on the association of ABCB1 variants and antidepressant treatment outcome in patients with MD (overall n = 2695). We investigated the association of treatment outcome and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015, rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status, ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a nominally significant association across all studies (P = 0.035, SNP was studied in a total of 2,037 patients) and a significant Bonferroni-corrected association among inpatients (P = 1.5 × 10(-05) , n = 485). Also SNP rs2235015 was significantly associated with antidepressant treatment outcome withstanding Bonferroni correction (P = 3.0 × 10(-04) ) among inpatients in a smaller subsample (n = 195). There were no significant associations of the other SNPs tested with antidepressant treatment outcome. Future pharmacogenetic association studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant outcome prediction.

show abstract

Section: Introductionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

Breitenstein

Brückl

Ising

et al. 2015

American J of Med Genetics Pt B

View full text Add to dashboard Cite

show abstract

“…Thus, genetic variations in P‐gp might affect the response to treatment, remission and side effects risk . Up to the present, although some research studies of major depressive disorder (MDD) and psychosis have shown an influence of ABCB1 polymorphisms in treatment outcome , in most cases, these results could not be replicated .…”

mentioning

confidence: 86%

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

Saiz‐Rodríguez

Belmonte

Román

et al. 2018

Basic Clin Pharma Tox

View full text Add to dashboard Cite

P-glycoprotein, encoded by ABCB1, is an ATP-dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P-glycoprotein expression; therefore, homozygous T/T could show higher plasma levels. Our aim was to evaluate the effect of C3435T on pharmacokinetics of 4 antipsychotics (olanzapine, quetiapine, risperidone and aripiprazole) and 4 antidepressants (trazodone, sertraline, agomelatine and citalopram). The study included 473 healthy volunteers receiving a single oral dose of one of these drugs, genotyped by real-time PCR. Multivariate analysis was performed to adjust the effect of sex and genotype of the main cytochrome P450 enzymes. C3435T polymorphism had an effect on olanzapine pharmacokinetics, as T/T individuals showed lower clearance and volume of distribution. T/T individuals showed lower T of 9-OH-risperidone, but this difference disappeared after multivariate correction. T/T homozygous individuals showed lower dehydro-aripiprazole and trazodone area under the concentration-time curve, along with lower half-life and higher clearance of trazodone. C/T genotype was associated to higher citalopram maximum concentration. C3435T had no effect on quetiapine, sertraline or agomelatine pharmacokinetics. C3435T can affect the elimination of some drugs in different ways. Regarding risperidone, trazodone and dehydro-aripiprazole, we observed enhanced elimination while it was reduced in olanzapine and citalopram. However, in quetiapine, aripiprazole, sertraline and agomelatine, no changes were detected. These results suggest that P-glycoprotein polymorphisms could affect CNS drugs disposition, but the genetic factor that alters its activity is still unknown. This fact leads to consider the analysis of ABCB1 haplotypes instead of individual variants.

show abstract

“…This gene encodes the P-glycoprotein (P-gp), a plasma membrane transporter that has a critical role in the regulation of the blood-brain barrier transportation of many drugs, including antidepressants [24]. 2 polymorphisms, 1 non-synonymous SNP (G2677T or rs2032582) and 1 synonymous SNP (C3435T or rs1045642), have been associated with altered P-glycoprotein activity [25,26]. Animal studies have indicated that many antidepressants are significant P-gp substrates while others are not [27].…”

Section: Introduction ▼mentioning

confidence: 99%

One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms

et al. 2016

View full text Add to dashboard Cite

Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in and remission, recovery, and suicide risk. This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between and remission or recovery. However, a significant association was observed between the G2677T polymorphism and suicide attempts. Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.

show abstract

Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study

Cited by 32 publications

References 57 publications

ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms

Contact Info

Product

Resources

About