Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study
- 231 Downloads
Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [123I]ADAM and single photon emission computed tomography (SPECT).
Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [123I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake.
At 6 h after the last dose, mean SERT occupancies were 81.5 ± 5.4% (mean±SD) for escitalopram and 64.0 ± 12.7% for citalopram (p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 ± 12.1% for escitalopram and 49.0 ± 11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain.
The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.
KeywordsSERT Occupancy Escitalopram Citalopram [123I]ADAM SPECT 5-HTT
- Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ, WFSBP Task Force on Treatment Guidelines for Unipolar Depressive Disorders (Allain H, Anderson I, Ayuso-Gutierrez JL, Baldwin D, Bech P, Benkert O, Berk M, Bitter I, Bourgeois ML, Burrows G, Cassano G, Cetkovich-Bakmas M, Cookson JC, da Costa D, Gheorghe MD, Heinze G, Higuchi T, Hirschfeld RM, Höschl C, Hoelsboer-Trachsler E, Kasper S, Katona C, Keller MB, Kulhara P, Kupfer DJ, Lecrubier Y, Leonard B, Licht RW, Lingjaerde O, Lublin H, Mendlewicz J, Mitchell P, Paykel ES, Puzynski S, Rush AJ, Rybakowski JK, Schweitzer I, Unützer J, Vestergaard P, Vieta E, Yamada K) (2002) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: acute and continuation treatment of major depressive disorder. World J Biol Psychiatry 3:5–43PubMedCrossRefGoogle Scholar
- Baumann P, Larsen F (1995) The pharmacokinetics of citalopram. Rev Contemp Pharmacother 6:287–295Google Scholar
- Herold N, Uebelhack K, Franke L, Amthauer H, Luedemann L, Bruhn H, Felix R, Uebelhack R, Plotkin M (2006) Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [(123)I]-ADAM. J Neural Transm 113:659–670PubMedCrossRefGoogle Scholar
- Klein N, Sacher J, Geiss-Granadia T, Attarbaschi T, Mossaheb N, Lanzenberger R, Pötzi C, Holik A, Spindelegger C, Asenbaum S, Dudczak R, Tauscher J, Kasper S (2006) In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects treated with different doses of escitalopram or citalopram. Psychopharmacology 3:263–272CrossRefGoogle Scholar
- Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, Ginovart N, Spencer EP, Cheok A, Houle S (2004) Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry 161:826–835PubMedCrossRefGoogle Scholar
- Noble S, Benfield P (1997) Citalopram: a review of its pharmacology, clinical efficacy and tolerability in the treatment of depression. CNS Drugs 8:410–432Google Scholar
- Sacher J, Asenbaum S, Klein N, Geiss-Granadia T, Mossaheb N, Pötzi C, Attarbaschi T, Lanzenberger R, Dudczak R, Kasper S, Tauscher J (2006) [123I]ADAM: a novel SPECT ligand for quantification of serotonin transporters in humans. Int J Neuropsychopharmacology Feb. 17, 1--8 [Epub ahead of print]Google Scholar