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

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-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. Conclusion: 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.