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

• Published in: Psychopharmacology Vol. 189; no. 2; pp. 145 - 153
• Main Authors: Catafau, Ana M, Perez, Victor, Plaza, Pedro, Pascual, Juan-Carlos, Bullich, Santiago, Suarez, Marina, Penengo, Maria M, Corripio, Iluminada, Puigdemont, Dolors, Danus, Monica, Perich, Javier, Alvarez, Enric
• Format: Journal Article
• Language: English
• Published: 01.12.2006
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-006-0540-y

Rationale: To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo super(123)I-ADAM SPECT. Objectives: super(123)I-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 super(123)I-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. super(123)I-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 sub(max) model. Results: Mean SERTocc values were 66.4 plus or minus 9.5% in midbrain, 63.0 plus or minus 9.6% in thalamus, and 61.3 plus or minus 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 plus or minus 0.15; thalamus = 0.85 plus or minus 0.13; striatum = 0.70 plus or minus 0.07) and healthy volunteers (midbrain = 1.19 plus or minus 0.22; thalamus = 0.96 plus or minus 0.14; striatum = 0.67 plus or minus 0.15). The E sub(max) model returned a SERTocc sub(max) = 70.5% and a Cp sub(50) = 2.7 ng/ml. Conclusions: Using super(123)I-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 sub(max) model is suitable for the study of paroxetine Cp relationship to super(123)I-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic-pharmacodynamic relationships in drug development.