Abstract
Few studies have demonstrated in vivo alterations of human serotonin and dopamine transporters (SERTS and DATS) during antidepressant treatment. The current study measured these transporter availabilities with [123I]β-CIT single photon emission computed tomography (SPECT) during administration of selective serotonin reuptake inhibitors (SSRIs) or a non-SSRI, bupropion. A total of 17 healthy human subjects were randomly assigned to two different treatment protocols: (1) citalopram (40 mg/day) followed by augmentation with bupropion (100 mg/day) or (2) bupropion (100–200 mg/day) for 16 days. Citalopram significantly inhibited [123I]β-CIT binding to SERT in brainstem (51.4%) and diencephalon (39.4%) after 8 days of administration, which was similarly observed after 16 days. In contrast, citalopram significantly increased striatal DAT binding by 15–17% after 8 and 16 days of administration. Bupropion and its augmentation to citalopram did not have a significant effect on DAT or SERT. In 10 depressed patients who were treated with paroxetine (20 mg/day), a similar increase in DAT and inhibition of SERT were observed during 6 weeks treatment. The results demonstrated the inhibition of SERT by SSRI in human in vivo during the chronic treatment and, unexpectedly, an elevation of DAT. This apparent SSRI-induced modulation of the dopamine system may be associated with the side effects of these agents, including sexual dysfunction.
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Acknowledgements
The authors gratefully acknowledge the technical support of M Early and A Perez for imaging, S Giddings for subject recruitment, and L Amici and N Sheung for radiochemistry. This work was supported in part by funds from Pfizer Inc., NARSAD Independent Investigator Award (RT Malison), and Japan Foundation for Aging and Health (PI, S Yamawaki, Hiroshima University).
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Kugaya, A., Seneca, N., Snyder, P. et al. Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration. Neuropsychopharmacol 28, 413–420 (2003). https://doi.org/10.1038/sj.npp.1300036
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DOI: https://doi.org/10.1038/sj.npp.1300036
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