Paroxetine in major depression:: Correlating plasma concentrations and clinical response

Background: In analogy to tricyclic antidepressants, serum concentrations of selective serotonin reuptake inhibitors (SSRIs) are frequently measured in order to optimize treatment results. However, clinical evidence for this approach is sparse. Methods: Forty patients with major depression were treated with paroxetine 20 mg/day for 14 days and with 40 mg/day for further 49 days. Treatment response measured by Hamilton depression rating scales (HAMD) was correlated with paroxetine plasma concentrations. Results: There was a significant difference between paroxetine plasma levels at 20 and 40 mg/day, respectively [20mg/d: median 24 (range 4-358); 40mg/d: 92 (30-398)]. However, the interindividual variance was very large. 18 out of 40 patients responded to paroxetine treatment. Conclusions: Receiver operated characteristic (ROC) analysis suggested no upper or lower limit of response. Responder had significantly higher paroxetine levels at day 7 [responder: 33 (4-107); non-responder: 13 (3-77)] but not at the end of the study [responder 93 (30-361); non-responder: 94 (59-398)]. Furthermore, plasma levels were not related to adverse events, age, body weight or severity of depression. These findings do not support any need for a routine screening of paroxetine plasma concentrations in clinical practice.