Evidence-Based Reviews

Perimenopausal depression? Ask how she’s sleeping

Current Psychiatry. 2005 June;4(6):39-53

Consider insomnia in workup of midlife mood disorders.

References

1. Owens JF, Matthews KA. Sleep disturbance in healthy middle-aged women. Maturitas 1998;30:41-50.

2. Perlis ML, Giles DE, Buysse DJ, et al. Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord 1997;42(2-3):209-12.

3. Bromberger JT, Assmann SF, Avis NE, et al. Persistent mood symptoms in a multiethnic community cohort of pre- and perimenopausal women. Am J Epidemiol 2003;158:347-56.

4. Sherwin BB. Changes in sexual behavior as a function of plasma sex steroid levels in post-menopausal women. Maturitas 1985;7(3):225-33.

5. Brizendine L. Minding menopause. Psychotropics vs estrogen: What you need to know now. Current Psychiatry 2003;2(10):12-31.

6. Anderson E, Hamburger S, Liu JH, Rebar RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 1987;156(2):428-33.

7. Obermeyer CM, Reynolds RF, Price K, Abraham A. Therapeutic decisions for menopause: results of the DAMES project in central Massachusetts. Menopause 2004;11(4):456-65.

8. Kravitz HM, Ganz PA, Bromberger J, et al. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause 2003;10(1):19-28.

9. Young T, Rabago D, Zgierska A, et al. Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 2003;26(6):667-72.

10. Wassertheil-Smoller S, Shumaker S, Ockene J, et al. Depression and cardiovascular sequelae in postmenopausal women. Arch Intern Med 2004;164:289-98.

11. Altshuler LL, Cohen LS, Moline ML, et al. The expert consensus guideline series. Treatment of depression in women. Postgrad Med 2001;March:1-107.

12. Krystal AD. Insomnia in women. Clin Cornerstone 2003;5(3):41-50.

13. Freedman RR. Physiology of hot flashes. Am J Hum Biol 2001;13(4):453-64.

14. Freedman RR, Woodward S, Sabharwal SC. A2-adrenergic mechanism in menopausal hot flushes. Obstet Gynecol 1990;76(4):573-8.

15. Miller AG, Li RM. Measuring hot flashes: summary of a NIH workshop. Mayo Clin Proc 2004;79:777-81.

16. Joffe H, Soares CN, Cohen LS. Assessment and treatment of hot flushes and menopausal mood disturbance. Psychiatr Clin North Am 2003 Sep;26(3):563-80.

17. Montplaisir J, Lorrain J, Denesle R, Petit D. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause 2001;8(1):10-16.

18. Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002;20:1578-83.

19. Guttoso T, Jr, Kurlan R, McDermott MP, Kieburtz K. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2003;101:337-45.

20. Kessel B, Kronenberg F. The role of complementary and alternative medicine in management of menopausal symptoms. Endocrinol Metab Clin North Am 2004;33:717-39.

21. National Institutes of Health. National Center for Complementary and Alternative Medicine. Office of Dietary Supplements. Questions and answers about black cohosh and the symptoms of menopause. Available at: http://ods.od.nih.gov/factsheets/blackcohosh.asp. Accessed May 9, 2005.

22. Ivarsson T, Spetz AC, Hammar M. Physical exercise and vasomotor symptoms in postmenopausal women. Mauritas 1998;29:139-46.

23. Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001;163:608-13.

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Trying to treat depression or anxiety in a midlife woman without asking how she’s sleeping may doom your treatment plan. Asking about sleep addresses issues that affect her quality of life and can provide valuable insight into effective interventions.

Psychiatric, psychosocial, and medical problems can disturb sleep during perimenopause.¹ To help you diagnose and treat both mood disorders and insomnia, this article:

describes how irregular hormone levels and psychosocial changes are linked to perimenopausal mood and sleep disorders
offers evidence-based strategies for hormone replacement therapy (HRT), antidepressants, hypnotics, and psychotherapy.

DEPRESSION AND INSOMNIA AT MIDLIFE

Sixty-five percent of women seeking outpatient treatment for depression report disturbed sleep.² Even mild anxiety and depression can undermine sleep quality, whereas insomnia can precede other symptoms of an evolving major depression.

Depressive disorders affect up to 29% of perimenopausal women (depending on the assessment tool used), compared with 8% to 12% of premenopausal women. Menopausal symptoms—hot flashes, poor sleep, memory problems—and not using HRT are associated with depression.³

Causes of midlife depression. Gonadal hormone changes have been implicated as a cause of increased depression in midlife women; declines in serum estradiol and testosterone are inversely associated with depression.⁴ The natural menopause transition (perimenopause) begins during the mid-40s, persists to the early 50s, and lasts an average 2 to 9 years. Estradiol produced by the ovary becomes erratic then decreases. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) serum levels increase, then plateau and serve as laboratory markers of menopause.⁵

Sociodemographic factors also may contribute to depression, anxiety, and insomnia. A midlife woman may experience role transitions—such as children leaving home and aging parents needing care. She may be adapting to her or her spouse’s retirement or to the loss of her partner by divorce or death. She may be grappling with her own aging and questions about mortality and life purpose.

In the workup, consider medical factors that may worsen sleep problems, such as hot flashes, sleep apnea, thyroid disease, urinary frequency, chronic pain, restless leg syndrome, caffeine use, sedentary lifestyle, and primary insomnia. Some women lose sleep from a bed partner’s snoring or movement (“spousal arousal”). Stimulating drugs such as theophylline can also play a role.

SLEEP CHANGES AT PERIMENOPAUSE

Sleep changes are among the most common physical and psychological experiences healthy women describe during perimenopause:

100 consecutive women surveyed at a menopause clinic reported fatigue (91%), hot flashes (80%), insomnia and early awakenings (77%), and depression (65%).⁶
Sleep problems were reported by >50% of 203 women interviewed for the Decisions at Menopause Study (DAMES).⁷
Difficulty sleeping across 2 weeks was reported by 38% of a multiethnic population of 12,603 women ages 40 to 55.⁸

Sleep problems occur more often during perimenopause than earlier in life. In a clinic sample of 521 women, Owens et al¹ found insomnia in 33% to 36% of those in premenopause and in 44% to 61% of women during perimenopause. In the total sample of healthy middle-aged women, 42% had sleep complaints, including:

initial insomnia: 49%
middle insomnia: 92%
early morning awakening: 59%.

No association? Individuals experience sleep quality subjectively, and these assessments may not match those obtained objectively. The Wisconsin Sleep Cohort Study,⁹ for example, found no association between menopause and diminished sleep quality in polysomnographic studies of 589 community-dwelling women. Even so, the peri- and postmenopausal women in the study reported less sleep satisfaction than premenopausal women did.

Most clinicians agree that a woman’s subjective experience of sleep is clinically relevant. Thus, rule out underlying sleep disorders before you attribute a midlife woman’s depressive signs and symptoms primarily to menopause.¹⁰

Treatment. Combination therapy may be useful, depending on the patient’s psychiatric and medical comorbidities (Algorithm).

TREATING PERIMENOPAUSAL DEPRESSION

HRT. Before the Women’s Health Initiative (WHI),¹⁰ guidelines recommended HRT for a first depressive episode during perimenopause and antidepressants for severe depressive symptoms and for women with a history of depression.¹¹ This practice changed when the WHI found risks of thromboembolism, breast cancer, stroke, and coronary artery disease that increased over time with HRT.

HRT remains a short-term treatment option but is no longer considered the first or only approach to mood symptoms at perimenopause. Discuss with your patient potential benefits of short-term HRT for a first episode of depression—especially if she has vasomotor symptoms—versus potential risks.

Antidepressants can improve perimenopausal depression, but few studies have tested these agents’ effects on sleep. To reduce treatment-associated insomnia:

select a relatively sedating antidepressant such as mirtazapine
accept some insomnia for 3 to 4 weeks, until a stimulating antidepressant has had a full ffect on mood and its associated side effects would be expected to resolve
or augment the antidepressant with a hypnotic such as zolpidem, zaleplon, eszopiclone, or trazodone.