Evidence-Based Reviews

Perimenopausal depression: Covering mood and vasomotor symptoms

Current Psychiatry. 2008 October;7(10):39-50

References

1. Schmidt PJ, Rubinow DR. Reproductive ageing, sex steroids and depression. J Br Menopause Soc 2006;12(4):178-85.

2. Rasgon N, Shelton S, Halbreich U. Perimenopausal mental disorders: epidemiology and phenomenology. CNS Spectr 2005;10(6):471-8.

3. Greene JG. Constructing a standard climacteric scale. Maturitas 1998;29(1):25-31.

4. Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54(5):573-83.Erratum in: Biol Psychiatry. 2003;54(5):585.

5. Feld J, Halbreich U, Karkun S. The association of perimenopausal mood disorders with other reproductive-related disorders. CNS Spectr 2005;10(6):461-70.

6. Avis NE, Stellato R, Crawford S, et al. Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Soc Sci Med 2001;52:345-56.

7. Campbell S, Whitehead M. Oestrogen therapy and the menopause syndrome. Clin Obstet Gynecol 1977;4:31-47.

8. Schmidt PJ, Rubinow DR. Menopause-related affective disorders: a justification for further study. Am J Psychiatry 1991;48:844-52.

9. Soares CN. Menopausal transition and depression: who is at risk and how to treat it? Expert Rev Neurother 2007;7(10):1285-93.

10. Prior JC. The complex endocrinology of menopausal transition. Endocrinol Rev 1998;19:397-428.

11. Rasgon N, Altshuler LL, Fairbanks LA, et al. Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. J Clin Psychiatry 2002;63(suppl):45-8.

12. Altshuler LL, Cohen LS, Moline ML, et al. The Expert Consensus Guideline Series. Treatment of depression in women. Postgrad Med 2001 Mar;(Spec No):1-107.

13. The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701-12.

14. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-33.

15. Ockene JK, Barad DH, Cochrane BB, et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA 2005;294:183-93.

16. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 2004;291:2947-58.

17. Shumaker SA, Legault C, Rapp SR. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289:2651-62.

18. FDA approves new labeling and provides new advice to postmenopausal women who use or who are considering using estrogen and estrogen with progestin [FDA Fact Sheet January 8, 2003]. Available at: http://www.fda.gov/oc/factsheets/WHI.html. Accessed September 11, 2008.

19. 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(5):780-6.

20. Cohen LS, Soares CN, Joffe H. Diagnosis and management of mood disorders during the menopausal transition. Am J Med 2005;118(suppl 12B):93-7.

21. Kahn DA, Moline ML, Ross RW, et al. Depression during the transition to menopause: a guide for patients and families. Postgrad Med 2001 Mar;(Spec No):110-1.

22. Alder J, Besken KE, Armbruster U, et al. Cognitive-behavioural group intervention for climacteric syndrome. Psychother Psychosom 2006;75(5):298-303.

23. 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(6):529-34.

24. Otto MW, Smits JA, Reese HE. Combined psychotherapy and pharmacotherapy for mood and anxiety disorders in adults: review and analysis. Clinical Psychology: Science and Practice 2005;12:72-86.

25. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomized, placebo controlled trial. J Affect Disord 2000;60:121-30.

26. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry [American Psychiatric Association subcommittee report]. J Clin Psychiatry 2006;67:1954-67.

27. Otto MW, Church TS, Craft LL, et al. Exercise for mood and anxiety disorders. J Clin Psychiatry 2007;68:669-76.

Although no randomized trials have examined psychotherapies for perimenopausal depression, a pilot open trial provided group CBT—psychoeducation, group discussion, and coping skills training—to 30 women with climacteric symptoms. Anxiety, depression, partnership relations, overall sexuality, hot flushes, and cardiac complaints improved significantly, based on pre- and post-intervention surveys. Sexual satisfaction and the stressfulness of menopausal symptoms did not change.²²

Clinical Point

We recommend that all women who present with perimenopausal depression receive information about psychotherapy

Integrative medicine. Plant-based substances and herbal remedies such as phytoestrogens, red-clover isoflavones, black cohosh, and evening primrose oil have been included in a few research investigations, and the evidence is equivocal. Because of potential interactions between alternative therapies and medications, inquire about their use. Although a comprehensive review of integrative medicine for perimenopausal symptoms is beyond the scope of this article, see suggested readings (Box).

Box

Integrative medicine treatments for perimenopausal symptoms: Suggested resources

Albertazzi P. Non-estrogenic approaches for the treatment of climacteric symptoms. Climacteric 2007;10(suppl 2):115-20.
Blair YA, Gold EB, Zhang G, et al. Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women’s Health Across the Nation. Menopause 2008;15:32-43.
Freeman MP, Helgason C, Hill RA. Selected integrative medicine treatments for depression: considerations for women. J Am Med Womens Assoc 2004;59(3):216-24.
Mischoulon D. Update and critique of natural remedies as antidepressant treatments. Psychiatr Clin North Am 2007;30:51-68.
Thachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affect Disord 2007;97:23-35.
Tremblay A, Sheeran L, Aranda SK. Psychoeducational interventions to alleviate hot flashes: a systematic review. J North Am Menopause Soc 2008;15:193-202.

Clinical recommendations

Explore options with your patient; discuss side effects, risks, and expected minimum duration of treatment. Antidepressants, hormonal therapies, psychotherapy, and complementary and alternative treatments each might have a role in managing perimenopausal depression. A patient’s preferences, psychiatric history, and depression severity help determine which options to consider and in what order. How she responded to past treatments also can help you individualize a plan.

Clinical Point

Integrative medicine appeals to many patients but has not been sufficiently studied in perimenopausal depression

HRT may be appropriate for women who express a preference for HRT, have responded well to past hormone therapy, and have no personal history or high-risk factors for breast cancer. Based on the WHI findings, we consider a history of breast cancer in the patient or a first- or second-degree relative a contraindication to HRT.

Estrogen can be used alone or with an antidepressant. Studies support 17β-estradiol, 0.1 to 0.3 mg/d, for 8 to 12 weeks.^11,23 Concomitant progesterone may be indicated to offset the effects of unopposed estrogen in women with an intact uterus. This option calls for an informed discussion with the patient about risks and benefits.

No data support long-term use of estrogen for recurrent or chronic depression. Because HRT’s risks and benefits vary with the length of exposure, individualize the extended use of estrogen solely to augment treatment for depression. Because vasomotor symptoms may recur when HRT is discontinued,¹⁵ we recommend that women make an informed decision in consultation with a gynecologist or primary care physician.

Antidepressants that have serotonergic activity—such as SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs)—appear most promising for treating comorbid depressive and vasomotor symptoms. If a patient has had a good response to an antidepressant in the past, consider starting with that medication.

Common antidepressant side effects are difficult to assess in perimenopausal patients with MDD because the symptoms attributed to antidepressant side effects—such as low libido, sleep disturbance, and weight changes—also can be caused by mood disorders and hormonal changes. Therefore, inquire about these symptoms when you initiate antidepressant therapy and at follow-up assessments.

Psychotherapy. We recommend that all women who present with perimenopausal depression receive information about psychotherapy. Psychotherapy alone often is adequate for mild depression, and adding psychotherapy to antidepressant treatment usually enhances recovery from moderate and severe depression episodes. In addition, patients who engage in psychotherapy for depression may have a lower rate of relapse.²⁴

Individual psychotherapy can help patients with perimenopausal depression:

accept this life transition
recognize the benefits of menopause, such as no need for contraception
develop awareness of personal potential in the years ahead.

Because depression often occurs in an interpersonal context, consider including family members in psychotherapy to improve the patient’s interpersonal support.

Integrative therapies. A full evaluation and consideration of standard treatment options is indicated for all women with MDD. Integrative medicine appeals to many patients but has not been sufficiently studied for perimenopausal depression. Supplemental omega-3 fatty acids and folate are reasonable adjuncts to the treatment of MDD^25-27 and deserve study in perimenopausal MDD.