Paroxetine inhibits norepinephrine uptake
in patients suffering from major depression
The selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor, paroxetine, has been suspected of having a blocking activity on norepinephrine (NE) uptake. To elucidate this point, the effect of paroxetine on the human NE transporter in patients with major depression has been studied.
Fifty two out-patients, diagnosed with major depression according to DSM-IV and a depression rating score > 20 at baseline on Montgomery Asberg scale, were enrolled in an open-label, parallel group, fixed-titration study. Subjects were randomly assigned to receive up to 60 mg/day of paroxetine or up to 30 mg/day of desipramine in a 3-to-1 ratio, respectively. NE and 5-HT transporter function was measured in cells transfected with human transporter cells in the presence of serum taken at baseline and at each end of week of treatment.
The inhibition of NE uptake by paroxetine was 27% and 43% at an average serum concentration of 100 ng/ml and 200 ng/ml, respectively. At these paroxetine concentrations, the inhibition of 5-HT uptake was more than 85%. Desipramine induced 85% inhibition of NE uptake at 100 ng/ml, and 18% and 51% inhibition of 5-HT uptake at 100 ng/ml and 500 ng/ml, respectively.
These results show that paroxetine is a 5-HT AND NE uptake inhibitor in vivo and should be reclassified as such. It should be noted however that the activities on the two neurotransmitters are not equal as is the case with the SNRI antidepressants such as milnacipran or duloxetine. The additional action on NE uptake may be involved in the therapeutic efficacy of paroxetine to treat conditions such as generalized anxiety, social anxiety, panic disorder, post-traumatic disorder and depression.
Am J Pyschiatry 159: 1702-1710, 2002
