Research on Treatment of Perimenopausal Depression
Hormonal Therapy and Depression
Only a few studies have specifically looked at the effect of hormonal therapy on depressed perimenopausal women. Four early studies found no improvement of depression in response to treatment with estrogen (Schneider et al., 1977; Shapira, Oppenheim, & Zohar, 1985; Coope, 1981; Coope, Thomson, & Poller, 1975). However, two recently reported small placebo-controlled trials of estradiol for the treatment of women with major or minor depressive disorders showed positive effects of estradiol on depression among perimenopausal women (Schmidt et al., 2000; Soares, Almeida, Joffe, & Cohen, 2001). The Schmidt et al. study found a positive effect for women with and without hot flashes. Participants in both studies met the DSM-III or DSM-IV criteria for depression and treatment was with estrogen alone. In both of these studies, estradiol was administered transdermally which provides greater hormonal stability.
Estrogen therapy for the treatment of depression, however, is more complicated. One complication is that women with an intact uterus are recommended to take estrogen combined with a progestin. Progesterone, however, may be associated with an increase in depressive symptomatology and reduce (or negate) any beneficial effects of estrogen (Magos et al., 1986; Sherwin, 1991; Sherwin & Gelfand, 1989). The previously mentioned studies only looked at estrogen alone. In addition, both estrogen and estrogen combined with a progestin are not without risk and have not been approved for the treatment of depression. The recent results from the Women's Health Initiative provide evidence of the increased risks of stroke, pulmonary embolism, coronary heart disease, and breast cancer associated with long-term use of combined therapy (Writing Group for Women's Health Initiative Investigators, 2002).
Estrogen Augmentation to Antidepressants
Two studies that examined adding estrogen to imipramine among depressed women did not find that estrogen provided any additional benefit over imiparmine (Prange, 1972; Shapira et al., 1985). One reported nonrandomized study examined the effect of hormone replacement therapy (HRT) with fluoxetine among women over age 60 with major depression (Schneider et al., 1997). They found that response to fluoxetine was significantly better than placebo among HRT users, whereas fluoxetine did not differ from placebo among non-HRT users. However, it is important to note that the fluoxetine groups showed similar response rates regardless of HRT use. Estrogen combined with tricyclic antidepressants (TCAs) may induce rapid mood cycling in some patients or lead to problematic side effects (Haynes & Parry, 1998). However, Schatzberg reported findings that postmenopausal women not on estrogen may respond better and have fewer side effects on TCAs than selective serotonic reuptake inhibitors (SSRIs; Haynes & Parry, 1998). Clearly we need better research on the interactions between different antidepressants and estrogen.
Although research on short-term psychotherapy specifically for menopausal women has not been reported, there is general support for its effectiveness in treating depression. Research has shown that interpersonal therapy and cognitive behavioral therapy can be as effective as antidepressant medication (McGrath, Keita, Strickland, & Russo, 1990).
Implication for Research and Treatment of Women During the Menopausal Transition
Implementation of Research to Improve Treatment and Enhance Prevention of Depression
In the area of prevention, research findings suggest that certain factors may increase a woman's vulnerability to depression during the menopausal transition. These particularly include a history of PMS and/or postpartum depression. This suggests that gynecologists and primary care physicians should be aware of a woman's history of depression during other times of hormonal changes and potentially screen at-risk women for depression. Clinicians should also be aware that women with a prior history of depression may be more prone to depression during the transition. Although there is no evidence at this time that menopause-related depression can be prevented, early detection might decrease severity and length of depression
In the area of treatment, research presented here clearly suggests that depression seen among women during the menopausal transition can be attributed to many factors, each of which has a different implication for treatment. Clinicians need to determine the source of depression among their patients prior to recommending treatment. The majority of depression at this time can be attributed to nonmenopause-related factors such as a prior history of depression, health problems, or social circumstances. In such cases, treatment would be no different than at any time. If patients are bothered by significant night sweats and sleep disruption, have no history of prior depression, and appear to have no medical or social circumstances that may account for depression, then strategies to reduce vasomotor symptoms may improve mood and decrease depression. Although hormonal therapy may be one option for women experiencing minor mood swings as a result of vasomotor symptoms, the side effects of progesterone may exacerbate or cause depressive symptoms. Women with a history of depression or depression unassociated with menopausal symptoms would likely benefit more from established treatments for depression such as antidepressants, or interpersonal or cognitive therapy. If an antidepressant is considered, a clinician should be cautious of potential interactions if a woman is on estrogen.
Research Findings to Inform Health Care Policy and Enhance Service Delivery
The widely-held belief that the menopausal transition is associated with depression does a disservice to women. Women who may be depressed during this time and in need of treatment may attribute their depression to menopause and think it is a normal part of menopause. Women need to be made aware that depression is not a normal concomitant of menopause and that they should seek treatment if they feel depressed. Women need greater awareness of what is and is not “normal,” how to screen their own symptoms, and when and where to seek help. We clearly need to educate both the general public and clinicians to detect symptoms of depression and to know that they are not a normal part of menopause. It is always a particular challenge to reach women who may not have access to care or who do not seek treatment for depression. This is a broader issue rather than one specific to the menopausal transition. We need to educate a wide variety of both health and service providers to recognize depression and to destigmatize it and to expand access to mental health services.
- Avis, Nancy; Depression during the menopausal transition; Psychology of Women Quarterly; Jun 2003; Vol. 27; Issue 2.
Reflection Exercise #7
The preceding section contained information
about research on perimenopausal and menopausal depression. Write three case study examples
regarding how you might use the content of this section in your practice.
Online Continuing Education QUESTION 14
What type of therapy has been shown to be as effective as antidepressant medication in postmenopausal depression?
Record the letter of the correct answer the