Expert Consensus Guideline Series
Depression During the Transition to Menopause:
A Guide for Patients and Families
David A. Kahn, M.D., Margaret L. Moline, Ph.D., Ruth W. Ross, M.A., Lori L. Altshuler, M.D., and Lee S. Cohen, M.D.
t is a common myth that as women enter the meno-
states. Mood disorders are biological illnesses believed to be
pausal years, it is “normal” to feel depressed. Serious
caused by changes in brain chemistry, and the tendency to
Idepression, however, should never be viewed as a “nor- depression is sometimes inherited genetically. Physical or
mal” event, and women who suffer from it at any time in life
emotional stress can trigger the biological changes that occur
should receive the same attention as for any other medical
in depression, and the hormonal changes leading up to meno-
illness. This guide is intended to answer commonly asked
pause may also trigger such changes, especially in women who
questions about depression that occurs around menopause.
may be prone to depression because of underlying brain
Depression affects up to 25% of women at some point in
chemistry or family history.
their lives, a far higher proportion than is seen among men.
The symptoms of major depression include:
Depression can be a debilitating disease, limiting daily activity
• Depressed mood most of the day, nearly every day for 2
as much as severe arthritis or heart disease. Large-scale research
weeks or longer and/or
studies have shown that most problems with depression begin
• Loss of interest or pleasure in activities that the person usu-
when women are in their 20s or younger. It is actually unusual
for depression to appear for the first time after menopause,
Other symptoms can include:
when all menstruation has ceased. However, there is a transi-
• Fatigue or lack of energy
tional time in mid-life known as perimenopause when women
• Restlessness or feeling slowed down
become somewhat more vulnerable to depression. This is the
• Feelings of guilt or worthlessness
time when menstrual periods gradually lighten and become
• Difficulty concentrating
less frequent. The transition to complete menopause may last
• Trouble sleeping or sleeping too much
anywhere from a few months to a few years.
• Recurrent thoughts of death or suicide.
Minor mood problems, insomnia, and hot flashes are com-
Mood disorders like major depression are not the fault of
mon during perimenopause. In some women, these symptoms
the person suffering from them or the result of a “weak” or
progress to a more severe mood disorder known as major de-
unstable personality. Rather, they are treatable medical ill-
pression. The risk for major depression is greatest in women
nesses for which there are specific medications and psycho-
who have a history of depression in the past or who had de-
therapy approaches that help most people.
pression after childbirth (postpartum depression). Women
who have had problems with depressed mood around the time
HOW IS DEPRESSION ASSESSED IN A WOMAN
of their menstrual periods (premenstrual dysphoric disorder)
may also be at higher risk for major depression in perimeno-
pause. And some women do become depressed for the first
A woman who feels depressed and thinks she also may be
time in their lives during perimenopause.
entering menopause should be evaluated by a gynecologist to
Several theories have been proposed to explain the increase
determine whether her symptoms could be related to the hor-
in depression during perimenopause. A traditional psychologi-
monal transition. She should also see a psychiatrist or other
cal view is that the “empty nest syndrome” or other aspects of
mental health professional, especially if her depression is severe
middle age lead to feelings of loss and sadness. More recently,
or if she has been depressed in the past. As part of the evalua-
scientists have focused on the biological effects of hormonal
tion, the doctor will:
fluctuations on mood, since this is a time when the ovaries
• Take a careful history of current and past symptoms, both
begin to make less estrogen. Estrogen interacts with chemicals
emotional and physical
in the brain that can affect mood. In some women, the de-
• Perform a physical exam and do blood tests to evaluate the
crease in estrogen during perimenopause may lead to depres-
function of the woman’s ovaries (if she is still having some
sion. Hot flashes and insomnia during this transition may also
menstrual periods) and thyroid gland (which may cause de-
cause emotional distress.
pression when underactive)
Many treatments for depression during perimenopause have
• Ask about life stressors that may be affecting the woman.
been suggested, but most have not yet been evaluated in sci-
entific studies. We therefore recently surveyed 36 leading ex-
perts in this field about the treatment of major depression in
relation to menopause. The recommendations described in
Treatment recommendations for major depression that occurs
this article are based on the results of this survey.
in association with menopause depend on how severe the
woman’s symptoms are and whether she has had previous epi-
WHAT IS MAJOR DEPRESSION?
sodes of depression.
Whenever symptoms are severe, the experts recommend
Major depression is a kind of illness called a mood disorder
treatment with antidepressant medication, generally in combi-
that affects a person’s ability to experience normal mood
nation with hormone replacement therapy (usually estrogen plus
• A POSTGRADUATE MEDICINE SPECIAL REPORT • MARCH 2001
TREATMENT OF DEPRESSION IN WOMEN
progesterone, or occasionally estrogen alone). The combination
symptoms. However, it is often combined with estrogen (ex-
of an antidepressant and hormones is advised whether or not the
cept in women who have had a hysterectomy) to ensure that
woman has had depression in the past.
excessive buildup of the uterus does not occur, which may lead
If the woman’s symptoms are relatively mild and she has
to a risk of cancer. The major disadvantage of progesterone
never been depressed before, experts do not agree on a single
can be uncomfortable side effects such as bloating, headaches,
best strategy but suggest trying hormones or antidepressants, 1
and even mood changes. Should side effects occur, different
at a time. Hormone replacement therapy by itself will usually
forms and dose schedules of progesterone may help.
relieve physical symptoms such as hot flashes and will sometimes
Depression is sometimes a side effect of hormone re-
improve mood significantly. On the other hand, some women
placement therapy, for reasons that are not understood. (It
prefer to avoid hormones, especially if they have few physical
may also occur in some younger women who take birth
symptoms, and may do better with an antidepressant.
control pills.) When this happens in a woman who has never
In women who are clearly in menopause rather than transi-
been depressed before, it may help to try a different hormone
tion, the experts believe that antidepressant medication is more
preparation. However, in women who have significant histo-
likely to relieve depression than hormone replacement. How-
ries of depression and become depressed again when starting
ever, many women should consider hormone replacement for its
hormone replacement therapy, the experts usually advise
other health benefits.
treating with antidepressant medication and/or stopping
In all of these situations, experts also recommend the use of
psychotherapy along with whatever medication is chosen. Just
working with a psychotherapist, however, is unlikely to help
severe depression unless medication is used as well.
Two types of psychotherapy are highly recommended for
depression related to menopause. Interpersonal therapy focuses
on understanding how changing human relationships may
Many types of antidepressants are available, with different
contribute to, or relieve, depression. Cognitive-behavioral ther-
chemical mechanisms of action and potential side effects. For
apy focuses on identifying and changing the pessimistic
women with depression associated with menopause, the experts
thoughts and beliefs that accompany depression. When used
prefer a type of antidepressant that affects a brain chemical called
alone, psychotherapy usually works more gradually than medi-
serotonin. These medications are called selective serotonin re-
cation, taking 2 months or more to show its full effects. How-
uptake inhibitors (SSRIs). Among these, the expert panel prefers
ever, the benefits may be long-lasting. Psychotherapy is usually
fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) as
combined with medication in major depression. It is unlikely
first choices, with citalopram (Celexa) an alternative.
to help severe depression if used by itself.
SSRIs can have the following side effects: nervousness, in-
somnia, restlessness, nausea, diarrhea, and sexual problems.
What if the first treatment isn’t helping?
Side effects differ from 1 person to another. Also, what may be
It is important to give each treatment strategy enough time
a side effect for 1 person (e.g., drowsiness) may benefit some-
to work before considering another. If hormones are tried first,
one else (e.g., a woman with insomnia). Fortunately, most
a response should be seen within 2-4 weeks. If the response is
women with depression do not have many problems with side
not satisfactory, the experts strongly suggest adding an antide-
effects from the SSRIs. To try to reduce the risk of side effects,
pressant. If an antidepressant is used first, it must be adjusted
many doctors start with a low dose and increase it slowly. If
to a high enough dose, and then given for at least 1–2 months
you are having problems with side effects, tell your doctor
to tell if it will help. If an SSRI antidepressant does not work
right away. If side effects persist, your doctor may lower the
in this time frame or produces intolerable side effects and has
dose or suggest trying a different SSRI.
to be stopped sooner, the experts strongly recommend
switching to a second SSRI. The doctor may also suggest
combining the SSRI with a second medication, which could
While antidepressants are the most appropriate treatment for
be either another kind of antidepressant, or hormone replace-
severe major depression in perimenopausal women, estrogen
ment therapy if not already in use.
may also be appropriate for mild to moderate symptoms, par-
ticularly if the woman has never been depressed before. Studies
are underway to compare estrogen and antidepressants and to
FOR MORE INFORMATION
determine for which patients estrogen may be preferred. Estro-
gen can be given either as a pill (e.g., Premarin, Estrace, and
American Menopause Foundation, Inc. (AMF)
Estratab) or through the skin by a patch. The woman should
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discuss the benefits and risks of each formulation with her doc-
tor. There is no doubt that estrogen controls the physical
New York, NY 10118
symptoms of menopause, especially hot flashes. There is contro-
versy over how long it should be taken and whether its other
general health benefits, such as keeping bones strong and possi-
North American Menopause Society
bly preventing memory problems and heart disease, may be
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outweighed by risks of breast cancer and stroke.
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Progesterone, the other major female hormone, does not by
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itself treat or prevent perimenopausal depression or physical
MARCH 2001 • A POSTGRADUATE MEDICINE SPECIAL REPORT •