PET measurement of serotonin transporter occupancy: a comparison of escitalopram and citalopram
Open accessAbstract
The selective serotonin reuptake inhibitor (SSRI) citalopram (R,S-citalopram) is a racemic compound of two enantiomers. On the basis of in-vitro studies, inhibition of the human serotonin transporter (5-HTT) is achieved by the S-enantiomer (S-citalopram or escitalopram). The aim of the present PET study was to compare 5-HTT occupancy after single equimolar doses (with respect to S-enantiomer) in humans in vivo using R,S-citalopram (20 mg) and S-citalopram (10 mg) using PET and the radioligand [(11)C]MADAM. The design was a single-dose, double-blind, two-way crossover study in eight healthy male subjects. The 5-HTT binding potential at baseline and after single doses of study drugs was used to calculate 5-HTT occupancy in seven brain regions. Serum concentrations of the study drugs were determined in order to calculate the apparent inhibition constant (K(i),(app)), a secondary parameter of interest for the comparison. In all brain regions examined, occupancy was numerically higher after treatment with R,S-citalopram [66+/-19% to 78+/-17% (mean+/-s.d.) depending on the region] than after S-citalopram (59+/-15% to 69+/-13%; overall comparison: F=14.8, d.f.=1, 90, p<0.001). In line with this the apparent inhibition constant was significantly lower for R,S-citalopram than for S-citalopram (overall comparison: F=6.7, d.f.=1, 90, p<0.05). The small but significant difference in occupancy and K(i),(app) found between R,S-citalopram and S-citalopram suggests that not only S-citalopram but also R-citalopram to some degree occupies the 5-HTT in the human brain in vivo.
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After exclusions, 16 articles reporting 17 unique studies were included.
“a total of 16 articles (reporting on 17 unique studies) were included [17–19, 28–40].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [19]
Eight studies excluded participants taking other possibly interacting medications.
“Eight studies excluded participants taking other possibly interacting medications (e.g., other psychotropic drugs or substances with high affinity for SERT) [19, 31, 32, 37–40, 42].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [19]
Two studies mentioned having standardized the time of day of drug administration and scanning.
“Two studies mentioned having standardized the time of day of drug administration and scanning [19, 35].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [19]
Five of 17 studies included non-smokers only, while the remaining studies did not mention smoking status.
“Five of 17 studies included non-smokers only, while the remaining studies did not mention smoking status [19, 30, 35, 39, 40].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [19]
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- Authors
- Lundberg, J., Christophersen, J. S., Petersen, K. B., Loft, H., Halldin, C., & Farde, L.
- Affiliations
- Karolinska Institutet (SE)
- Lundbeck (Denmark) (DK)
- Corresponding author
- Lundberg, Johan
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-04
- Volume
- 10
- Issue
- 06
- Pages
- 777-85
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2163385892
- Cited by
- 55
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 3 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 1 · 2012: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet (09114)
- H. Lundbeck A/S
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- serotonin transporter, citalopram, escitalopram, enantiomers, selective serotonin reuptake inhibitors, binding potential, neuroimaging, healthy volunteers
- MeSH terms
- Adult, Antidepressive Agents, Benzylamines, Brain, Humans, Magnetic Resonance Imaging, Male, Stereoisomerism, Structure-Activity Relationship, Citalopram, Selective Serotonin Reuptake Inhibitors, Radiopharmaceuticals, Positron-Emission Tomography, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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