title: Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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-HT(1A)) gene were determined by PCR analysis.
  
  
  RESULTS
  Multiple regression analysis revealed that the plasma concentrations of PAX, 5-HTTLPR genotype, and -1019C/G 5-HT(1A) 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-HT(1A) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Mikito
authors.initials: M
authors.lastname: Ueda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Saeki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Akiyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D017374:Paroxetine; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human