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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-12

AUTHORS

Ana M. Catafau, Victor Perez, Pedro Plaza, Juan-Carlos Pascual, Santiago Bullich, Marina Suarez, Maria M. Penengo, Iluminada Corripio, Dolors Puigdemont, Monica Danus, Javier Perich, Enric Alvarez

ABSTRACT

RATIONALE: To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo (123)I-ADAM SPECT. OBJECTIVES: (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 (123)I-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. (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 (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 (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 (max) model is suitable for the study of paroxetine Cp relationship to (123)I-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic-pharmacodynamic relationships in drug development. More... »

PAGES

145-153

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00213-006-0540-y

    DOI

    http://dx.doi.org/10.1007/s00213-006-0540-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010787173

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17033844


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