Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder

Ishiguro, Shin; Watanabe, Takashi; Ueda, Mikito; Saeki, Yoshinori; Hayashi, Yasuhiko; Akiyama, Kazufumi; Saito, Atsushi; Kato, Kazuko; Inoue, Yoshimasa; Saito, Kazutaka

doi:10.1007/s00228-011-1073-9

Cited by 23 publications

(22 citation statements)

References 28 publications

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“…Last but not the least, we did not nd the relationship between other gene polymorphisms and treatment response to sertraline. This is inconsistent with previous studies that found the 5-HT1A receptor -1019C/G polymorphism was strongly associated with response to treatment in PD receiving sertraline or paroxetinethe [54,59]. Another study suggested that the genetic variant of the COMT enzyme may be related to treatment response to paroxetine in PD [60].…”

Section: Discussioncontrasting

confidence: 81%

The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder

Zou

Huang

Wang

et al. 2020

Preprint

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Background: A number of studies have shown that genetic factor plays an important role in etiology of panic disorder (PD). The aim of the present study was to examine the association of serotonin-related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug. Methods: 233 patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), 5-HTR1A rs6295, 5-HTR2A rs6313 and COMT rs4680 gene polymorphisms were genotyped and assessed for the potential association. Results: The allelic model showed that the SLC6A4 rs140701 polymorphism variant was significantly associated with increased risk of PD (OR = 0.624, 95 % CI 0.450-0.864, p <0.05), and a significant result was found in the dominant model (OR = 0.546; 95% CI, 0.371-0.804, p <0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95 % CI 0.128-0.328; OR = 0.249, 95 % CI 0.155-0.401, both p <0.001), indicating the PD patients with S-allele had a poorer response to sertraline than L-allele carriers. Conclusion s : The present study suggests that the SLC6A4 rs140701 polymorphism variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertraline in the treatment of PD.

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Section: Discussioncontrasting

confidence: 81%

The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder

Zou

Huang

Wang

et al. 2020

Preprint

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“…However, we failed to find the relationship between others gene polymorphisms and treatment response to sertraline. which is inconsistent with previous studies that found the 5-HT1A receptor − 1019C/G polymorphism was strongly associated with response to treatment in PD receiving sertraline or paroxetinethe [49,53]. In another study suggest that the genetic variant of the COMT enzyme may be related to treatment response to paroxetine in PD [54].…”

Section: Discussioncontrasting

confidence: 81%

Association between serotonin - related gene polymorphisms and e arly effects of sertraline in Chinese Han patients with panic disorder

Zou¹,

Huang²,

Wang³

et al. 2020

Preprint

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Objective The aim of the present study was to examine the association of serotonin -related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug. Methods 230 patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), HTRA1 rs6295, HTR2A rs6313 and COMT rs4680 genes were genotyped and assessed for allele. Results The allelic model showed that the SLC6A4 rs140701 variant was significantly associated with increased risk of PD(OR = 0.624, 95% CI 0.450-0.864, p <0.05), and significant results was found in the dominant model(OR = 0.546; 95% CI, 0.371-0.804, p <0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128-0.328; OR = 0.249, 95% CI 0.155-0.401, both p <0.001), and indicated the PD patients with S-allele had a poorer response to sertraline than L-allele carriers. Conclusions The present study suggest that the SLC6A4 rs140701 variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertralines in the treatment of PD.

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“…Body weight ranged from 40–95 kg (57.9±11.4 kg). The PD patients in this study were part of the subject group (n=65) in our previous study 9. Out of 65 patients, 52 subjects with PD without MDD were selected, and their raw data from the clinical evaluations and the genotyping of 5-HTTLPR were used and reanalyzed in the present study.…”

Section: Methodsmentioning

confidence: 99%

Factors affecting discontinuation of initial treatment with paroxetine in panic disorder and major depressive disorder

Aoki¹,

Ishiguro²,

Watanabe³

et al. 2014

NDT

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ObjectiveThe aims of the present study were to analyze the association between discontinuation of paroxetine (PAX) and the genetic variants of the polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in Japanese patients with panic disorder (PD) and major depressive disorder (MDD).MethodsThe 5-HTTLPR genotype was determined by polymerase chain reaction method. PAX plasma concentration was measured by high-performance liquid chromatography to confirm adherence.ResultsWhen comparing between the PD and MDD patients with the chi-square test and Fisher’s exact test, the PD patients had a significant and higher discontinuation rate due to non-adherence than did the MDD patients (13.5% [7/52] versus 0% [0/88], respectively; P<0.001). MDD patients had a significant and higher discontinuation rate due to untraceability than PD patients (12.5% [11/88] versus 1.9% [1/52]; P=0.032). Multilogistic regression revealed a tendency for the long/short and short/short genotypes to affect discontinuation due to adverse effects in PD patients (25.0% versus 6.3%, respectively; P=0.054).ConclusionThe results indicate that the 5-HTTLPR genotype might contribute to the discontinuation of initial PAX treatment due to adverse effects in PD patients.

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Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder

Abstract: The present study revealed that plasma concentration of PAX, 5-HTTLPR genotype, -1019C/G 5-HT(1A) genotype, PAS score at baseline, and adverse effects may influence the therapeutic response to PAX in patients with PD.

Cited by 23 publications

References 28 publications

The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder

The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder

Association between serotonin - related gene polymorphisms and e arly effects of sertraline in Chinese Han patients with panic disorder

Factors affecting discontinuation of initial treatment with paroxetine in panic disorder and major depressive disorder

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