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