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Inverse correlation between clinical response to paroxetine and plasma drug concentration in patients with major depressive disorders
Author(s) -
YasuiFurukori Norio,
Nakagami Taku,
Kaneda Ayako,
Inoue Yoshimasa,
Suzuki Akihito,
Otani Koichi,
Kaneko Sunao
Publication year - 2011
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.1252
Subject(s) - paroxetine , medicine , major depressive episode , plasma concentration , major depressive disorder , depression (economics) , rating scale , psychology , gastroenterology , antidepressant , developmental psychology , macroeconomics , hydrocortisone , amygdala , hippocampus , economics
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. Copyright © 2011 John Wiley & Sons, Ltd.