A Canadian multicenter,
double-blind study of paroxetine and fluoxetine in major depressive disorder
Chouinard G, Saxena B, Belanger MC,
Ravindran A,
Bakish D, Beauclair L, Morris P, Vasavan Nair NP,
Manchanda R, Reesal R, Remick R, O'Neill MC
Hopital Louis-H. Lafontaine and Allan Memorial Institute,
Montreal, Quebec, Canada.
J Affect Disord 1999 Jul; 54(1-2):39-48
ABSTRACT
BACKGROUND: Recent studies have
suggested clinical differences among selective serotonin reuptake
inhibitors. In a 12-week randomized, multicenter, double-blind trial, the
antidepressant and anxiolytic efficacy of the selective serotonin reuptake
inhibitors paroxetine and fluoxetine was compared in patients with moderate
to severe depression.
METHODS: A total of 203 patients were randomized to
fixed doses (20 mg/day) of paroxetine or fluoxetine for the first six weeks
of therapy. From week 7-12, dosing could be adjusted biweekly, as required (paroxetine
20-50 mg/day, and fluoxetine 20-80 mg/day). The mean prescribed doses were
paroxetine 25.5 mg/day (range 20.0-40.2 mg/day), and fluoxetine 27.5 mg/day
(range 20.0-59.5 mg/day). Emergence of motor nervousness or restlessness was
assessed using the ESRS scale for akathisia.
RESULTS: Both active treatments demonstrated
comparable antidepressant efficacy (HAM-D, CGI). Anxiolytic activity of the
two drugs (COVI, STAI, HAM-D) was also comparable. However, paroxetine was
found to be superior to fluoxetine on two subscore measures at week 1 of
therapy (HAM-D Agitation item, p < 0.05; Psychic Anxiety item, p <
0.05), with no differences detected after week 2. The overall incidence of
adverse effects was comparable in the two treatment groups. Constipation,
dyspepsia, tremor, sweating and abnormal ejaculation were more common in
paroxetine-treated subjects, whereas nausea and nervousness were more
frequent in fluoxetine-treated patients. Weight loss was more common in the
fluoxetine versus paroxetine group (11.88% versus 2.94%, respectively). ESRS
scores for akathisia were low throughout the study and showed little
change.
LIMITATIONS: Differences observed between the two
drugs in antianxiety effects were limited to two measures of anxiety among
several others.
DISCUSSION: The data indicate that paroxetine and
fluoxetine have comparable antidepressant and anxiolytic efficacy. Paroxetine appears to produce an earlier improvement in agitation and
psychic anxiety symptoms compared with fluoxetine.