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Abstract: Background: Bupropion is thought to exert its antidepressive effect by blocking the dopamine transporter (DAT). The purpose of this study was to evaluate the DAT activity in depressed patients by means of 99mTc-TRODAT-1 SPECT in relation to the efficacy of bupropion treatment. Methods: In 12 healthy controls and 16 depressed patients the baseline DAT activity was examined. Nine of the 16 patients went through an additional second SPECT investigation, after 4 weeks of bupropion treatment. Results: In the depressed patients, the baseline DAT striatum–occipital ratio (SOR) (1.04±.36, mean±SD) was not significantly different from that in the control group (1.12±.33) (p >.05). Correlation was found between baseline SOR and HAM-D score change (r =−.745, p =.02) of the bupropion treated patients. The average DAT occupancy due to the bupropion treatment was 20.84±27.7%. No significant correlation between the therapeutical effectiveness and the occupancy was observed. Limitations: One of the limiting factors of our study has been the lack of drug monitoring. Conclusions: In good agreement with other PET studies, we found 20.84% DAT occupancy during bupropion treatment. The lack of correlation between the efficacy of therapy and occupancy of DAT may raise the question as to whether other mechanisms are involved in the effect of bupropion. [Copyright &y& Elsevier]