Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder:: a 123I-ADAM SPECT study

Rationale To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo I-123-ADAM SPECT. Objectives I-123-ADAM SPECT was used to investigate the SERTocc induced by paroxetine in major depression disorder (MDD) patients, to compare the SERT availability in drug-free MDD patients and healthy volunteers, and to study the relationship between paroxetine plasma concentrations (Cp) and SERTocc. Materials and methods Measures of SERT availability by means of I-123-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. I-123-ADAM SPECT measures of SERT availability from a group of ten previously studied age-matched healthy volunteers were used for comparison. The relationship between percentages of SERTocc and paroxetine Cp was studied using an E (max) model. Results Mean SERTocc values were 66.4 +/- 9.5% in midbrain, 63.0 +/- 9.6% in thalamus, and 61.3 +/- 10.9% in striatum. No significant differences in SERTocc were found among these three regions. No significant differences in mean SERT availability were found in any region between drug-free MDD patients (midbrain=1.14 +/- 0.15; thalamus=0.85 +/- 0.13; striatum=0.70 +/- 0.07) and healthy volunteers (midbrain=1.19 +/- 0.22; thalamus=0.96 +/- 0.14; striatum=0.67 +/- 0.15). The E (max) model returned a SERTocc(max)=70.5% and a Cp-50=2.7 ng/ml. Conclusions Using I-123-ADAM SPECT, treatment with paroxetine 20 mg/day leads to more than 60% SERTocc on average in cerebral regions with known high SERT density. Data from this study do not support the existence of SERT availability differences between drug-free MDD patients and healthy volunteers. Finally, the E (max) model is suitable for the study of paroxetine Cp relationship to I-123-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic-pharmacodynamic relationships in drug development.