Evidence-Based Reviews

Psychiatric considerations in menopause

Current Psychiatry. 2018 October;17(10):11-16,53

References

1. Bromberger JT, Kravitz HM. Mood and menopause: findings from the study of women’s health across the nation (SWAN) over 10 years. Obstet Gynecol Clin North Am. 2011;38(3):609-625.
2. Almeida OP, Marsh K, Flicker L, et al. Depressive symptoms in midlife: the role of reproductive stage. Menopause. 2016;23(6):669-765.
3. Sajatovic M, Friedman SH, Schuermeyer IN, et al. Menopause knowledge and subjective experience among peri- and postmenopausal women with bipolar disorder, schizophrenia and major depression. J Nerv Ment Dis. 2006;194(3):173-178.
4. Ayers BN, Forshaw MJ, Hunter MS. The menopause. The Psychologist. 2011;24:348-353.
5. Bromberger JT, Kravitz HM, Chang YF, et al. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychol Med. 2011;41(9):1879-1888.
6. Cohen LS, Soares CN, Vitonis AF, et al. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006;63(4):385-390.
7. Freeman EW, Sammel MD, Lin H, et al. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63(4):375-382.
8. Georgakis MK, Thomopoulos TP, Diamantaras AA, et al. Association of age at menopause and duration of reproductive period with depression after menopause: a systematic review and meta-analysis. JAMA Psychiatry 2016;73(2):139-149.
9. DiBonaventura MC, Wagner JS, Alvir J, et al. Depression, quality of life, work productivity, resource use, and costs among women experiencing menopause and hot flashes: a cross-sectional study [published online November 1, 2012]. Prim Care Companion CNS Disord. 2012;14(6): pii: PCC.12m01410. doi: 10.4088/PCC.12m01410.
10. Llaneza P, Garcia-Portilla MP, Llaneza-Suárez D, et al. Depressive disorders and the menopause transition. Maturitas. 2012;71(2):120-130.
11. Vivian-Taylor J, Hickey M. Menopause and depression: is there a link? Maturitas. 2014;79(2):142-146.
12. Kessler RC, McGonagle KA, Swartz M, et al. Sex and depression in the National Comorbidity Survey. 1: lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993;29(2-3):85-96.
13. Friedman SH, Stankowski JE, Sajatovic M. Bipolar disorder in women. The Female Patient. 2007;32:15-24.
14. Soares C, Cohen L. The perimenopause, depressive disorders, and hormonal variability. Sao Paulo Med J. 2001;119(2):78-83.
15. Friedman SH, Sajatovic M, Schuermeyer IN, et al. Menopause-related quality of life in chronically mentally ill women. Int J Psychiatry Med. 2005;35(3):259-271.
16. Schmidt PJ, Ben Dor R, Martinez PE, et al. Effects of estradiol withdrawal on mood in women with past perimenopausal depression: a randomized clinical trial. JAMA Psychiatry. 2015;72(7):714-726.
17. Carretti N, Florio P, Bertolin A et al. Serum fluctuations of total and free tryptophan levels during the menstrual cycle are related to gonadotrophins and reflect brain serotonin utilization. Hum Reprod. 2005;20(6):1548-1553.
18. Borrow AP, Cameron NM. Estrogenic mediation of serotonergic and neurotrophic systems: implications for female mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:13-25.
19. Hu LY, Shen CC, Hung JH et al. Risk of psychiatric disorders following symptomatic menopausal transition: a nationwide population-based retrospective cohort study. Medicine (Baltimore). 2016;95(6):e2800. doi: 10.1097/MD.0000000000002800.
20. Riecher-Rossler AW. Estrogens and schizophrenia. In: Bergemann N, Riecher-Rossler A, eds. Estrogen effects in psychiatric disorders. Wien, Austria: Springer-Verlag Wien; 2005:31-52.
21. Pope CJ, Oinonen K, Mazmanian D, et al. The hormonal sensitivity hypothesis: a review and new findings. Med Hypotheses. 2017;102:69-77.
22. Dennerstein L, Soares CN. The unique challenges of managing depression in mid-life women. World Psychiatry. 2008;7(3):137-142.
23. Caan B, LaCroix AZ, Joffe H, et al. Effects of estrogen and venlafaxine on menopause-related quality of life in healthy postmenopausal women with hot flashes: a placebo-controlled randomized trial. Menopause. 2015;22(6):607-615.
24. Seeman MV. Psychosis in women: Consider midlife medical and psychological triggers. Current Psychiatry. 2010;9(2):64-68,75-76.
25. Sajatovic M, Friedman SH, Sabharwal J, et al. Clinical characteristics and length of hospital stay among older adults with bipolar disorder, schizophrenia or schizoaffective disorder, depression, and dementia. J Geriatr Psychiatry Neurol. 2004;17(1):3-8.
26. Grover S, Talwar P, Baghel R, et al. Genetic variability in estrogen disposition: potential clinical implications for neuropsychiatric disorders. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(8):1391-1410.
27. Kulkarni J, Gavrilidis E, Wang W, et al. Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age. Mol Psychiatry. 2015;20(6):695-702.
28. Kulkarni J, Gavrilidis E, Gwini SM, et al. Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial. JAMA Psychiatry. 2016;73(9):947-954.
29. Brzezinski A, Brzezinski-Sinai NA, Seeman MV. Treating schizophrenia during menopause. Menopause. 2017;24(5):582-588.
30. Lange B, Mueller JK, Leweke FM, et al. How gender affects the pharmacotherapeutic approach to treating psychosis - a systematic review. Expert Opin Pharmacother. 2017;18(4):351-362.
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Treating mental illness in menopause

Changes to drug pharmacokinetics occur because some metabolising enzymes are estrogen-dependent and their levels decline after menopause, which leads to greater variability in drug response, particularly for oral medications. Other factors that can contribute to variability in medication response are polypharmacy, alcohol, illicit drugs, liver mass, smoking, caffeine, and nutritional intake.

While antidepressants are the first-line treatment for MDD and anxiety disorders, some patients remain unresponsive or inadequately responsive to currently available medications. In perimenopausal women with MDD, there may be an indication for adjunctive therapy with transdermal E2 in refractory cases; estrogen may augment the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants as well as hasten the onset of antidepressant action.²² Estrogen also may be worth considering in women with mild depressive symptoms. For MDD, SSRIs plus estrogen may be more beneficial in improving mood than either agent alone. The effectiveness of E2 is less certain in postmenopausal depression.

Hormonal therapy for mental health disorders has equivocal evidence. The individual’s history and risk factors (eg, cardiovascular and osteoporosis risks) must be considered. A recent trial found that treatment with either venlafaxine or low-dose estrogen improved quality of life in menopausal women with vasomotor symptoms.²³ Venlafaxine improved the psychosocial domain, while estrogen improved quality of life in other domains. Escitalopram, duloxetine, and citalopram have also been identified as having a possible positive impact on menopausal symptoms.²² SSRIs and serotonin-norepinephrine reuptake inhibitors may help reduce hot flashes and improve sleep.¹¹

Regarding schizophrenia and estrogen, there may be improved symptoms during the high estrogen phase of the menstrual cycle, followed by a premenstrual aggravation of symptoms. Recall that women have a second peak of onset of schizophrenia after age 45, around the age of the onset of menopause.²⁴ In a study of geropsychiatric hospital admissions, women were overrepresented among those with schizophrenia and schizoaffective disorder, compared with other psychiatric disorders.²⁵ Postmenopausally, some women experience a decreased responsiveness to antipsychotics and worsening symptoms. In menopausal women with schizophrenia, check prolactin levels to help determine whether they are experiencing a natural menopause or medication-induced amenorrhea. Gender differences in pharmacotherapy responses and the decreasing response to antipsychotics in women older than age 50 have been observed²⁶ and have led to exploration of the role of estrogen for treating schizophrenia in menopausal women. There have been contradictory results regarding use of estrogen as an adjunct to antipsychotics, with some reports finding this approach is effective and results in lower average doses of antipsychotics. Kulkarni et al^27,28 have reported improvements in positive symptoms of treatment-resistant schizophrenia with transdermal use of E2, 200 mcg, as an adjunct to antipsychotics in women of childbearing age. However, they expressed caution regarding the health risks associated with prolonged use of E2. Long-term risks of high-dose estrogen therapies include thromboembolism, endometrial hyperplasia, and breast cancer, and individual factors should be considered before starting any form of hormone therapy. Selective estrogen receptor modulators (SERMs), such as raloxifene, which can cause activation of E2 receptors in a tissue-specific fashion and have less estrogen-related adverse effects, offer hope for future development in this field.^27,28 While the use of adjunctive hormone therapy to manage psychotic symptoms in menopause is not routinely advised, the dosages of previously effective antipsychotics may need to be reviewed, or long-acting depot routes considered.²⁹ Increased risk of prolonged QTc interval and tardive dyskinesia in geriatric women also should be considered in decisions regarding changes to antipsychotics or dosages.³⁰

There are no guidelines regarding change in dosage of either individual antidepressants or antipsychotics in women at the time of menopause for managing pre-existing conditions. This may be due to the high variability in the effect of menopause on mental health and recognition that menopause is also a time for deterioration in physical health, as well as psychosocial changes for women, and thus other forms of intervention need to be considered.

Continued to: The biopsychosocial approach to treatment...

Psychiatric considerations in menopause

References

Treating mental illness in menopause

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