Context Standard therapy for hot flashes has been hormone replacement with estradiol
or progestational agents, but recent data suggest that antidepressants inhibiting
serotonin reuptake may also be effective.
Objective To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled
release [CR]) in treating the vasomotor symptoms displayed by a general cross-section
of menopausal women.
Design and Setting Randomized, double-blind, placebo-controlled, parallel group study conducted
across 17 US sites, including urban, suburban, and rural clinics.
Patients A total of 165 menopausal women aged 18 years or older experiencing
at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement
therapy for at least 6 weeks. Women were excluded if they had any signs of
active cancer or were undergoing chemotherapy or radiation therapy.
Intervention After a 1-week placebo run-in phase, study participants were randomized
to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in
a 1:1:1 ratio) for 6 weeks.
Main Outcome Measures Mean change from baseline to week 6 in the daily hot flash composite
score (frequency × severity).
Results Fifty-six participants were randomly assigned to receive placebo and
51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The
mean reductions in the hot flash frequency composite score from baseline to
week 6 were statistically significantly greater for those receiving paroxetine
CR than for those receiving placebo. By week 6, the mean daily hot flash frequency
went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and
from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine
CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo
group. Mean placebo-adjusted reduction in hot flash composite scores were
−4.7 (95% confidence interval, − 8.1 to −1.3; P = .007) comparing 12.5-mg/d paroxetine CR with placebo; and −3.6
(95% confidence interval, −6.8 to −0.4; P =
.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to
median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those
in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the
Conclusion Paroxetine CR may be an effective and acceptable alternative to hormone
replacement and other therapies in treating menopausal hot flash symptoms.