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

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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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.

Conflict of interest

The authors declare no biomedical or financial interests or potential conflicts of interest directly relevant to the content of the present study.

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Authors and Affiliations

  1. Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, 321–0293, Japan

    Shin Ishiguro, Takashi Watanabe, Mikito Ueda, Yoshinori Saeki, Yuki Hayashi & Kazutaka Shimoda

  2. Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, 321–0293, Japan

    Kazufumi Akiyama & Atsushi Saito

  3. Sakura La Mental Clinic, 6-13-16 Youtou, Utsunomiya, Tochigi, 321–0904, Japan

    Kazuko Kato

  4. Mitsubishi Tanabe Pharma Factory Ltd, 955 Koiwai, Yoshitomicho, Chikujo, Fukuoka, 871–8550, Japan

    Yoshimasa Inoue

Authors
  1. Shin Ishiguro
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  2. Takashi Watanabe
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  3. Mikito Ueda
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  4. Yoshinori Saeki
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  5. Yuki Hayashi
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  6. Kazufumi Akiyama
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  7. Atsushi Saito
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  8. Kazuko Kato
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  9. Yoshimasa Inoue
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  10. Kazutaka Shimoda
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Correspondence to Kazutaka Shimoda.

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Ishiguro, S., Watanabe, T., Ueda, M. et al. Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder. Eur J Clin Pharmacol 67, 1213–1221 (2011). https://doi.org/10.1007/s00228-011-1073-9

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  • DOI: https://doi.org/10.1007/s00228-011-1073-9

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