Paroxetine in Major Depression: Correlating Plasma Concentrations and Clinical Response

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. 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. There was a significant difference between paroxetine plasma levels at 20 and 40 mg/day, respectively [20 mg/d: median 24 (range 4-358); 40 mg/d: 92 (30-398)]. However, the interindividual variance was very large. 18 out of 40 patients responded to paroxetine treatment. 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.