Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder: a 123I-ADAM SPECT study
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To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo 123I-ADAM SPECT.
123I-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 123I-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. 123I-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 Emax model.
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 Emax model returned a SERToccmax = 70.5% and a Cp50 = 2.7 ng/ml.
Using 123I-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 Emax model is suitable for the study of paroxetine Cp relationship to 123I-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic–pharmacodynamic relationships in drug development.
Keywords123I-ADAM SPECT Serotonin transporter Serotonin transporter availability Major depression disorder Paroxetine Occupancy Pharmacology
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