Tailoring Treatment of Depression for Women Across the Reproductive Lifecycle:The Importance of Pregnancy, Vasomotor Symptoms, and Other Estrogen-Related Events in Psychopharmacology

Abstract

Compared with men, women are at increased risk of depression, especially at several reproductive-related lifecycle points. This may be partially due to changing levels of estrogen, a hormone that can affect levels of neurotransmitters and neural proteins. As estrogen levels vary throughout the lifespan, risk of depression in women also varies, and not all treatments are appropriate or effective at all times. In adolescence, onset of depression may be associated with onset of puberty, but treating underage girls with antidepressants can risk suicidality. In females of childbearing age, mood disturbances associated with menstrual cycles signal a risk for later full-blown major depressive disorder. In depressed pregnant and postpartum women, risks of treatment versus risks of nontreatment are intricate and require case-by-case evaluation. In perimenopause, vasomotor symptoms may be harbingers of oncoming depression and also may signal the presence of dysregulated hormones and neurotransmitters. Relieving vasomotor symptoms may be a necessary dimension of treating depression. In postmenopause, response to selected antidepressants may depend on whether the patient is also taking hormone-replacement therapy. To attain optimal outcomes, modern psychopharmacologists must tailor treatment of depression to a woman's reproductive stage of life. TRIMONOAMINE MODULATORS AND DEPRESSION Clinicians often target the three neurotransmitters most implicated in depression-serotonin (5-HT), norepinephrine (NE), and dopamine (DA)-by using antidepressants to block reuptake at the respective neurotransmitter reuptake transporters. 1 However, other agents can modulate all three neurotransmitters without

Vasomotor Symptoms and Depression in Women, Part 1: Role of Vasomotor Symptoms in Signaling the Onset or Relapse of a Major Depressive Episode

“…Clinically, perimenopausal women with vasomotor symptoms are 4 times more likely to be depressed than perimenopausal women without vasomotor symptoms. 6 The elevated risk seems to subside in postmenopause, when estrogen levels are low and when vasomotor symptoms also subside, 3 which agrees with observations that risk for depression and vasomotor symptoms correlate with hormonal fluctuations, not absolute levels. 3 Neurobiologically, both vasomotor symptoms and depression are regulated by the monoamine neurotransmitters serotonin, norepinephrine, and dopamine.…”

“…[1][2][3] Some changes are easily observed: starting around age 47, a woman's menstrual period changes in length, then whole cycles are skipped. Vasomotor symptoms, such as hot flashes (also called hot flushes) plus night sweats, often with sleep disturbances, mark the transitional years of late perimenopause into early postmenopause.…”

Reproductive Aging: Perimenopause and Psychopathological Symptoms

“…The majority of findings indicate an increased susceptibility to depression during the perimenopausal transition [76,77]. Perimenopausal depression is significantly associated with lower education, a rural background, a history of psychiatric illness in the family, a later age of menarche, and the late stage of perimenopause [56,58].…”

“…Vasomotor symptoms were reported to be harbingers of oncoming depression and also may signal the presence of dysregulated hormones and neurotransmitters [77]. Psychological aspects of perimenopause, such as loneliness and life satisfaction, were reported to be influenced by personal and partner issues, which seem to play a much more relevant role than biological aspects [81].…”

“…In treating depression in perimenopause, relieving vasomotor symptoms may be a necessary dimension [77]. In milder forms of menopausal mood distress, hormone replacement therapy may be sufficient.…”