Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study

Am J Psychiatry. 2001 Nov;158(11):1843-9. doi: 10.1176/appi.ajp.158.11.1843.

Abstract

Objective: Selective serotonin reuptake inhibitors are commonly used to treat major depression; however, the percentage of serotonin (5-HT) transporter (5-HTT) sites occupied during clinical dosing is unknown. This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked.

Method: Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT binding potential was measured with [(11)C]DASB and positron emission tomography, before and after 4 weeks of treatment. The binding potential is proportional to receptor density. Striatal 5-HTT binding potential was measured twice in six healthy subjects and once in 11 healthy subjects.

Results: A significant decrease in striatal 5-HTT binding potential was found after either treatment, compared to changes found over a 4-week period in healthy subjects. For patients treated with 20 mg/day of paroxetine (N=7), the mean proportion of 5-HTT sites occupied was 83%. For patients treated with 20 mg/day of citalopram (N=4), the mean 5-HTT occupancy was 77%. 5-HTT occupancy increased in a nonlinear relationship with serum levels of paroxetine such that a plateau of occupancy around 85% occurred for serum paroxetine levels greater than 28 microg/liter.

Conclusions: During treatment with clinical doses of paroxetine or citalopram, approximately 80% of 5-HTT receptors are occupied. This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential but may be necessary for some therapeutic effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Binding Sites
  • Biological Transport / physiology
  • Brain / metabolism*
  • Caudate Nucleus / metabolism
  • Chromatography, High Pressure Liquid
  • Citalopram / blood
  • Citalopram / pharmacokinetics*
  • Citalopram / therapeutic use*
  • Corpus Striatum / metabolism
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Gyrus Cinguli / metabolism
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / blood
  • Paroxetine / pharmacokinetics*
  • Paroxetine / therapeutic use*
  • Prefrontal Cortex / metabolism
  • Putamen / metabolism
  • Regression Analysis
  • Serotonin Uptake Inhibitors / blood
  • Serotonin Uptake Inhibitors / pharmacokinetics*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Thalamus / metabolism
  • Tomography, Emission-Computed*

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram
  • Paroxetine