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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1213-1221
Number of pages9
JournalEuropean journal of clinical pharmacology
Volume67
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Genetic polymorphism
  • Panic disorder
  • Paroxetine
  • Serotonin 1A receptor
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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