Estrogen therapy is still the best way to avert the sudden feelings
of overheating, sweating and occasionally palpitations - the most
common symptom of menopause - that can strike women from once a day
to once an hour, day and night.
The U.S. Food and Drug Administration approved one antidepressant
medication, the selective serotonin reuptake inhibitor (SSRI)
paroxetine, brand name Brisdelle, for treating hot flashes in 2013.
Brisdelle, marketed as Paxil when used as an antidepressant, was the
first non-hormonal option approved by the FDA.
Antidepressants are often used off-label to treat hot flashes, Dr.
Hadine Joffe of the department of Psychiatry at Brigham and Women’s
Hospital in Boston told Reuters Health. But at high doses, hormones
are more effective than antidepressants, she said.
Joffe led the new study, which compared venlafaxine, the generic
form of the antidepressant Effexor, against a lower dose of
In the trial, 97 women took half a milligram of low-dose estradiol
daily, 96 took 75 milligrams of venlafaxine per day and 140 women
took a placebo. All the study participants were menopausal or
post-menopausal with an average of eight hot flashes per day at the
Two months later, the estradiol group was having an average of 3.9
hot flashes per day and the venlafaxine group was having 4.4 hot
flashes. The placebo group had decreased to 5.5 per day.
Women were most satisfied with the estradiol, and least satisfied
with the placebo, according to results published in JAMA Internal
Medicine. About half the women taking venlafaxine said they were
satisfied with it.
The prevailing opinion is that estrogen treatment is more effective
than drugs like venlafaxine, Joffe said, but these results indicate
that the difference is small, and perhaps not meaningful, at a lower
“Part of it is that the estrogen dose we used was the low dose,
while the higher dose has gotten the most attention and is more
effective than the lower dose,” she said.
In 2012, the North American Menopause Society recommended that
hormone therapy be used at the lowest possible dose in light of the
large, long-term Women’s Health Initiative study that found a
connection between combination estrogen/progestin therapy used by
postmenopausal women and an increased risk of breast cancer, heart
disease and stroke.
But even at a low dose, hormone therapy was still more effective
than venlafaxine in the current study, Dr. James A. Simon said.
Simon is a professor of obstetrics and gynecology at George
Washington University in Washington, D.C. and was not involved in
the new study.
“The Women’s Health Initiative, which painted hormone therapy or
estrogen therapy in a very very negative light, made hormones much
more difficult for menopausal women to take even if they were highly
symptomatic with hot flashes,” he told Reuters Health.
Antidepressants like venlafaxine also have side effects, he noted.
In the new study, some women in the venlafaxine group experienced
nausea, stomach upset, sleepiness or high blood pressure.
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In 2011, the FDA did not approve the antidepressant desvenlafaxine
for treating hot flashes, even though the drug was effective,
because of safety concerns that included high blood pressure, he
“One of the major side effects of all the antidepressant-like drugs
are sexual, and sexual dysfunction is already a problem in the
menopausal population,” Simon said. “Some of them cause massive
weight gain as well.”
Case reports have indicated that serious withdrawal symptoms may
start within hours of going off venlafaxine.
While hot flashes are a normal aspect of menopause, they can
interfere with sleep and daily life for some women, and treating
them can improve quality of life, Dr. Heidi D. Nelson of Oregon
Health & Science University in Portland told Reuters Health.
There are a few other options that are neither antidepressants nor
hormones, including gabapentin, which treats pain syndrome, and an
older blood pressure medication, Joffe said, but those are not
For most women, hot flashes last for about four to five years, and
taking hormone therapy for that short amount of time should be safe,
Joffe said. But for some women, symptoms last longer. In that case
it may be a good idea to use venlafaxine to help come off or delay
going on hormone therapy, she said.
Weighing the risks and benefits of the two main treatment options
comes down to your personal health concerns, Joffe said.
In general, estrogen is less expensive, but costs vary by the type
of formulation, Nelson said.
For some women, like those with breast cancer, hormone therapy is
not an option.
If a woman tries hormone therapy and isn’t satisfied with the
effects or is bothered by side effects, she can switch to
venlafaxine, or vice versa, Joffe said.
“We’re in a strong position to say that we can hopefully
individualize this,” she said.
JAMA Internal Medicine, online May 27, 2014.
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