TY - JOUR
T1 - Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder
AU - Ishiguro, Shin
AU - Watanabe, Takashi
AU - Ueda, Mikito
AU - Saeki, Yoshinori
AU - Hayashi, Yuki
AU - Akiyama, Kazufumi
AU - Saito, Atsushi
AU - Kato, Kazuko
AU - Inoue, Yoshimasa
AU - Shimoda, Kazutaka
N1 - Funding Information:
Acknowledgments This research was supported by KAKENHI, Grants-in-Aid for Scientific Research and a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (JSPS) (no. 18591307) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (no. 19790837 and no. 18790847). The funding sources played no role in the study design, collection, analysis, or interpretation of data, writing the report, or the decision to submit the paper for publication.
PY - 2011/12
Y1 - 2011/12
N2 - Purpose: The objective of this study was to evaluate genetic and pharmacokinetic factors to establish the pharmacotherapeutic effect of paroxetine (PAX) in patients with panic disorder (PD). Method: Subjects were 65 drug-naïve patients who fulfilled the DSM-IV-TR criteria for PD diagnosis. All subjects were administered PAX (10 mg/day) for 4 weeks, and PD severity was assessed using the Panic and Agoraphobia Scale (PAS) at baseline and at 2 and 4 weeks after initiation of treatment. Plasma PAX concentration was determined by high-performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants and the -1019C/G promoter polymorphism of the serotonin 1A receptor (5-HT1A) gene were determined by PCR analysis. Results: Multiple regression analysis revealed that the plasma concentrations of PAX, 5-HTTLPR genotype, and -1019C/G 5-HT1A gene polymorphism were significant factors affecting clinical response to PAX (reduction ratio of PAS score) at 2 weeks after the initiation of pharmacotherapy. The -1019C/G 5-HT1A gene promoter polymorphism, PAS score at baseline, and adverse effects were found to be the significant factors affecting clinical response to PAX at 4 weeks after initiation of pharmacotherapy. Conclusion: The present study revealed that plasma concentration of PAX, 5-HTTLPR genotype, -1019C/G 5-HT1A genotype, PAS score at baseline, and adverse effects may influence the therapeutic response to PAX in patients with PD.
AB - Purpose: The objective of this study was to evaluate genetic and pharmacokinetic factors to establish the pharmacotherapeutic effect of paroxetine (PAX) in patients with panic disorder (PD). Method: Subjects were 65 drug-naïve patients who fulfilled the DSM-IV-TR criteria for PD diagnosis. All subjects were administered PAX (10 mg/day) for 4 weeks, and PD severity was assessed using the Panic and Agoraphobia Scale (PAS) at baseline and at 2 and 4 weeks after initiation of treatment. Plasma PAX concentration was determined by high-performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants and the -1019C/G promoter polymorphism of the serotonin 1A receptor (5-HT1A) gene were determined by PCR analysis. Results: Multiple regression analysis revealed that the plasma concentrations of PAX, 5-HTTLPR genotype, and -1019C/G 5-HT1A gene polymorphism were significant factors affecting clinical response to PAX (reduction ratio of PAS score) at 2 weeks after the initiation of pharmacotherapy. The -1019C/G 5-HT1A gene promoter polymorphism, PAS score at baseline, and adverse effects were found to be the significant factors affecting clinical response to PAX at 4 weeks after initiation of pharmacotherapy. Conclusion: The present study revealed that plasma concentration of PAX, 5-HTTLPR genotype, -1019C/G 5-HT1A genotype, PAS score at baseline, and adverse effects may influence the therapeutic response to PAX in patients with PD.
KW - Genetic polymorphism
KW - Panic disorder
KW - Paroxetine
KW - Serotonin 1A receptor
KW - Serotonin transporter
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U2 - 10.1007/s00228-011-1073-9
DO - 10.1007/s00228-011-1073-9
M3 - Article
C2 - 21688171
AN - SCOPUS:82455167894
SN - 0031-6970
VL - 67
SP - 1213
EP - 1221
JO - European journal of clinical pharmacology
JF - European journal of clinical pharmacology
IS - 12
ER -