Inverse correlation between clinical response to paroxetine and plasma drug concentration in patients with major depressive disorders.

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.