Depression and the menopause: why antidepressants are not enough?

BACKGROUND: Gender differences, related to varying sexual hormone levels and hormone secretion patterns across the lifespan, contribute to women's vulnerability to mood disorders and major depression. Women are more prone than men to depression, from puberty onwards, with a specific exposure across the menopausal transition. However, controversy still exists in considering fluctuation/loss of estrogen as a specific aetiologic factor contributing to depression in perimenopause and beyond. AIMS: To briefly review the interaction between changes in menopausal hormone levels, mood disorders, associated neuropsychological co-morbidities and ageing, and to evaluate the currently available therapeutic options for perimenopausal mood disorders: (a) treatment of light to moderate mood disorders with hormonal therapy (HT); (b) treatment of major depression with antidepressants; (c) the synergistic effect between HT and antidepressants in treating menopausal depression. RESULTS: Depression across the menopause has a multifactorial aetiology. Predictive factors include: previous depressive episodes such as premenstrual syndrome and/or postpartum depression; co-morbidity with major menopausal symptoms, especially hot flashes, nocturnal sweating, insomnia; menopause not treated with HT; major existential stress; elevated body mass index; low socioeconomic level and ethnicity. Postmenopausal depression is more severe, has a more insidious course, is more resistant to conventional antidepressants in comparison with premenopausal women and has better outcomes when antidepressants are combined with HT. CONCLUSION: The current evidence contributes to a re-reading of the relationship between menopause and depression. The combination of the antidepressant with HT seems to offer the best therapeutic potential in terms of efficacy, rapidity of improvement and consistency of remission in the follow-up.