Both noradrenergic and serotonergic systems have been implicated in the pathophysiology of
panic disorder. The advent of selective
serotonin (5-HT) reuptake inhibitors (
SSRIs) (e.g.
citalopram) and, more recently, selective noradrenergic (NA) reuptake inhibitors (NRIs) (e.g.
reboxetine) has provided potentially important avenues of treatment for the disorder. To date, the comparative efficacy of selective NA and
5-HT reuptake inhibitors for
panic disorder remains unresolved. Nineteen patients with
panic disorder were randomized in a single-blind, cross-over design to either
citalopram or
reboxetine for 8 weeks and after a 2-week washout were switched to the other study
drug. At week 18, seven of 13 patients (54%) in the intent-to-treat sample responded to
reboxetine and nine of 11 patients responded to
citalopram (82%). Both
citalopram and
reboxetine led to significant improvements in
panic attack severity with no apparent between-
drug differences in efficacy. However,
citalopram demonstrated superior efficacy in treating depressive symptoms. One non-responder to
citalopram responded to
reboxetine and three non-responders to
reboxetine responded to
citalopram. Although
SSRIs are viewed as a first-line treatment for
panic disorder, these results suggest that a NA agent such as
reboxetine may also have a role. These data also suggest an advantage for
citalopram in treating comorbid depressive symptoms, although some patients may respond preferentially to an SSRI and other patients to an NRI.