title: Inverse correlation between clinical response to paroxetine and plasma drug concentration in patients with major depressive disorders.
abstract: OBJECTIVE
  There are few data concerning a clear relationship between the clinical effect of paroxetine and plasma drug concentrations, although therapeutic ranges have been established for some tricyclic antidepressants.
  
  
  METHODS
  In this study, 120 patients with major depressive disorders were treated with 10-40 mg/day of paroxetine for 6 weeks, and a total of 89 patients completed the protocol. A clinical evaluation using the Montgomery-Asberg Depression Rating Scale (MADRS) was performed at 0, 1, 2, 4 and 6 weeks.
  
  
  RESULTS
  Significant correlations were found between the plasma concentrations of paroxetine and the percentage improvement in the total MADRS scores (r = -0.282, p < 0.01) and the final MADRS scores at 6 weeks (r = 0.268, p < 0.05). The conventional receiver-operating-characteristic curve showed the fraction of true positive results and false negative results for various cut-off levels of paroxetine concentration for response and remission. The thresholds for both response and remission that gave the maximal sensitivity and specificity for paroxetine concentrations were 64.2 ng/ml.
  
  
  CONCLUSIONS
  These results suggest that plasma paroxetine concentrations are negatively associated with improvement and that response occurs at the upper threshold of 64.2 ng/ml of paroxetine. These findings should be replicated with a larger patient sample.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. yasufuru@cc.hirosaki-u.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagami
authors.forename: Ayako
authors.initials: A
authors.lastname: Kaneda
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Akihito
authors.initials: A
authors.lastname: Suzuki
authors.forename: Koichi
authors.initials: K
authors.lastname: Otani
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood* / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015415:Biomarkers; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors