Psychopharmacology

, Volume 189, Issue 2, pp 145–153

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

  • 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
Original Investigation

Abstract

Rationale

To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo 123I-ADAM SPECT.

Objectives

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.

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 Emax model returned a SERToccmax = 70.5% and a Cp50 = 2.7 ng/ml.

Conclusions

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.

Keywords

123I-ADAM SPECT Serotonin transporter Serotonin transporter availability Major depression disorder Paroxetine Occupancy Pharmacology 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ana M. Catafau
    • 1
    • 2
  • Victor Perez
    • 3
  • Pedro Plaza
    • 2
  • Juan-Carlos Pascual
    • 3
  • Santiago Bullich
    • 2
  • Marina Suarez
    • 2
  • Maria M. Penengo
    • 2
  • Iluminada Corripio
    • 3
  • Dolors Puigdemont
    • 3
  • Monica Danus
    • 2
  • Javier Perich
    • 4
  • Enric Alvarez
    • 3
  1. 1.Experimental Medicine, Clinical Pharmacology Discovery MedicinePsychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKlineBarcelonaSpain
  2. 2.Centre for Imaging in Psychiatry, CRC-MarHospital del MarBarcelonaSpain
  3. 3.Psychiatry DepartmentHospital Sant PauBarcelonaSpain
  4. 4.Magnetic Resonance Department, CRC-MARHospital del MarBarcelonaSpain

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