Review of North American Menopause Society ‘Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations’

Endorsement by the IMS

Professor Wendy Wolfman

IMS Education Committee and Education Committee Members, Department of Obstetrics and Gynaecology, University of Toronto, Canada

The North American Menopause Society has developed an important guideline for the evaluation and treatment of perimenopausal depression [1]. This document, co-authored by an 11-member panel of experts and opinion leaders, who systematically reviewed the literature between 1980 and 2015 on depression and depressive symptoms, focuses on issues related specifically to perimenopause and postmenopausal women. The document reviews five relevant areas: epidemiology, clinical presentation, therapeutic effects of antidepressants and hormonal therapies as well as the efficacy of other therapies including psychotherapy, exercise and natural health products.

The IMS endorses this well-written comprehensive document that provides a summary and recommendations for improving the mental health of perimenopausal and menopausal women. Depressive symptoms are highly prevalent in at least 45% of perimenopausal women around the world. The paper confirms that the perimenopause is a time of vulnerability for the development of depression in women, particularly those who have had a prior episode of depression. The presentation may be complicated by perimenopausal symptomatology such as hot flushes, night sweats, sleep and sexual disturbances, weight changes and cognitive shifts. Evaluation involves identifying the menopausal stage and assessing psychiatric symptoms via validated screening tools. Proven therapeutic options include antidepressants such as SSRI and SNRI antidepressants, cognitive behavior therapy and other psychotherapies. For perimenopausal women, there is some evidence that estrogen therapy has antidepressant effects similar to antidepressant agents. However, estrogen alone is ineffective for depressive disorders in postmenopausal women. Estrogen may enhance the clinical response to antidepressants. This synergy needs to be evaluated in further research trials.

Some of the limitations of the document identified by the IMS reviewers included little mention of effects of other hormones on depression such as thyroid and adrenal hormones, and only a small mention of testosterone [2,3]. A section on directions for future research would have been useful in the document. For instance, comment could have been made about very important recent genetic research and its impact on depression, as noted in the recent review on gene polymorphisms and the risk of depression in menopausal women [4]. Also, there is currently a deficiency in the literature comparing doses, types, vehicles and timing of hormone therapies with regard to outcomes of depression. More research is needed to address the etiology and management of premature ovarian insufficiency-related depression as well as the synergistic effects of psychoactive medication with hormone therapies. These areas may prove to be relevant to address in future research recommendations.

In conclusion, we endorse this excellent guideline. We believe it validates the alterations in mental well-being that occur during the menopause transition, with the goal of improving the health of women around the globe.

Comment

Nicole Jaffe

Faculty of Health Sciences, University of the Witwatersrand and the Aurum Institute, South Africa

These new guidelines describe the challenges encountered by researchers in assessing and diagnosing midlife depression, including the indistinct and variable time span of the menopause transition which makes it difficult to pinpoint the exact onset of mood disorders; the absence of consensus in the definitions and severity of perimenopausal depression; and the dearth of standardized menopause-specific mood-disorder scales to evaluate midlife depression. In addition, depressive symptoms and menopausal symptoms often overlap, making it difficult to distinguish the specific symptoms of depression. Furthermore, certain symptoms of menopause may be a factor in increasing the level of perimenopausal depression, so it is essential to understand the different etiologies of these symptoms. The various symptoms that may co-occur with depression in women are reviewed in-depth. This will be especially helpful to clinicians in disentangling the symptoms that are common to both the menopause transition and depression, and should be carefully identified in order properly to treat the depression and, concurrently, the menopausal symptoms.

The authors discuss the available therapies for treating depression in peri- and postmenopausal women, including various antidepressants; hormone therapy, specifically estrogen therapy; psychotherapy and alternative/complementary medicine. At present, only desvenlafaxine has been studied and shown to be significantly effective in large, well-designed randomized controlled trials (RCTs) of severely depressed peri- and postmenopausal women [5], but several other small open trials of SNRIs and SSRIs have been shown to improve mood disorders, vasomotor symptoms (VMS) and sleep disturbances [6].

The role that MHT, specifically estrogen, may play in treating or potentiating the effect of antidepressants in women with peri- and postmenopausal depression is of great interest to clinicians and researchers. The guidelines indicate that, although some studies show that estrogen may augment the response of some SSRIs, the data are not conclusive. However, estrogen therapy has been shown in several studies, two of them RCTs, to be effective in treating depression (MDD, dysthymia or minor depression) in perimenopausal women [7], including both those with and without VMS. Recent research demonstrated the prophylactic effect of transdermal estrogen and intermittent micronized progesterone in preventing the development of depressive symptoms in euthymic perimenopausal women [8], but further research is needed before estrogen therapy can be recommended to prevent depression in these perimenopausal women.

Some small RCTs show that MHT may not be helpful in treating depression in postmenopausal women. The data on estrogen plus different progestogens in this population and in perimenopausal women are scarce and indecisive. There is, however, some evidence that hormonal contraceptives may provide relief from mood disorders as well as contraception in perimenopausal women.

The guidelines are extremely comprehensive, thorough and most welcome. They highlight the urgent need for further, in-depth research on evaluating, diagnosing, and treating peri- and postmenopausal depression, and, possibly, the use of estrogen in the early menopause transition to prevent the development of depressive symptoms.

References

1. Maki PM, Kornstein SG, Joffe H, et al. on behalf of the Board of Trustees for The North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause 2018;25. Epub ahead of print September 5
   http://www.ncbi.nlm.nih.gov/pubmed/30182804
2. Montgomery JC, Appleby L Brincat M, et al. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. Lancet 1987;1:297-9
   http://www.ncbi.nlm.nih.gov/pubmed/2880114
3. Studd J, Nappi RE. Reproductive depression. Gynecol Endocrinol 2012;28(Suppl 1):42-5
   http://www.ncbi.nlm.nih.gov/pubmed/22394303
4. Rozycka A, Slopien R, Slopien A, et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas 2016;84:42-54
   http://www.ncbi.nlm.nih.gov/pubmed/26620113
5. Clayton AH, Kornstein SG, Dunlop BW, et al. Efficacy and safety of desvenlafaxine 50 mg/d in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder. J Clin Psychiatry 2013;74:1010-17
   http://www.ncbi.nlm.nih.gov/pubmed/24229754
6. Soares CN, Arsenio H, Joffe H, et al. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: Impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause 2006;13:780-6
   http://www.ncbi.nlm.nih.gov/pubmed/16894334
7. Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: A double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001;58:529-34
   http://www.ncbi.nlm.nih.gov/pubmed/11386980
8. Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: A randomized clinical trial. JAMA Psychiatry 2018;75:149-57
   http://www.ncbi.nlm.nih.gov/pubmed/29322164

Content updated 10 September 2018