Perimenopausal depression: Covering mood and vasomotor symptoms
Hormones, antidepressants, or psychotherapy—what would you recommend?
Figure Biopsychosocial milieu of depression during perimenopauseHormonal fluctuation. The estrogen withdrawal theory7 explains depressive symptoms as resulting from a sustained decline in ovarian estrogen in tandem with spiking secretions of follicle-stimulating hormone by the pituitary. The finding that women with surgical menopause have a higher incidence of depressive symptoms than women with natural menopause supports this hypothesis.
Mood disorders occur across various female reproductive events, and increased risk appears to be associated with fluctuating gonadal hormones. Thus, declining estrogen may be less causative of perimenopausal depression than extreme fluctuations in estradiol activity.9,10
Estrogen interacts with dopamine, norepinephrine, beta-endorphin, and serotonin metabolism. In particular, estrogen facilitates serotonin delivery to neurons across the brain. These findings—and the success of selective serotonin reuptake inhibitors (SSRIs) in treating mood disorders—support the theory that fluctuating estrogen affects the serotonergic system and may cause depressive symptoms.
‘Domino theory.’ Others have hypothesized that depressive symptoms are the secondhand result of somatic symptoms of perimenopause. In a “domino effect,” hot flushes and night sweats disrupt women’s sleep, bringing fatigue and impaired daytime concentration, which lead to irritability and feelings of being overwhelmed.8
This theory, which incorporates perimenopausal hormone changes, is supported by elevated levels of depression in women who report frequent and intense vasomotor symptoms persisting >27 months.2
The psychosocial theory suggests that depression results from increased stress or adverse events.2 Midlife women with depressive symptoms report many possible sources of stress:
- demanding jobs
- family responsibilities
- dual demands of career and family
- little time for self
- poverty or employment stressors
- not enough sleep
- changing social relationships.
Negative interpretations of aging or the menopausal transition also have been implicated in cross-cultural studies.6 The predictive nature of psychosocial issues for depression during perimenopause supports this theory.
Evidence-based treatment
HRT. Research and clinical reports suggest that estrogen may have antidepressant effects, either alone or as an adjunct to antidepressant medication.11 Before the WHI studies, expert consensus guidelines on treating depression in women recommended HRT as first-line treatment for patients experiencing a first lifetime onset of mild to moderate depression during perimenopause.12 WHI findings since 2002 that associated HRT with increased risk of stroke, deep vein thrombosis, and pulmonary embolism—without clear protection against coronary heart disease or cognitive decline—have left HRT a controversial option for treating perimenopausal depression. In the WHI trials:
- 10,739 postmenopausal women age 50 to 79 without a uterus received unopposed conjugated equine estrogens, 0.625 mg/d, or placebo for an average 6.8 years.13
- 16,608 postmenopausal women age 50 to 79 with an intact uterus received combination HRT (conjugated equine estrogens, 0.625 mg/d, plus 2.5 mg of medroxyprogesterone), or placebo for an average 5.6 years.14
The study using combination HRT found increased risks of breast cancer, ischemic stroke, blood clots, and coronary heart disease.15 A follow-up study showed that vasomotor symptoms returned in more than one-half the women after they stopped using combination HRT.15
A companion WHI trial found that estrogen, 0.625 mg/d—given unopposed or with a progestin—did not prevent cognitive decline in women age 65 to 79 and may have been associated with a slightly greater risk of probable dementia.16,17
The FDA recommends that women who want to use HRT to control menopausal symptoms use the lowest effective dose for the shortest time necessary.18
Antidepressants. SSRIs may be more useful than estrogen for producing MDD remission in perimenopausal women.19 SSRIs and other psychotropics may reduce perimenopausal vasomotor symptoms in addition to addressing depressive symptoms (Table 3). When choosing antidepressant therapy, consider the patient’s dominant presenting perimenopausal symptoms and side effects associated with treatment.20
Table 3
Nonhormone medications for perimenopausal depression: Evidence-based dosages and target symptoms
| Medication | Dosage effective for perimenopausal depression | Symptoms assessed |
|---|---|---|
| SSRIs | ||
| Citaloprama | 40 to 60 mg | Depressive and vasomotor |
| Escitalopramb,c | 5 to 20 mg | Depressive and vasomotor |
| Fluoxetined | 20 to 40 mg | Depressive and vasomotor |
| Paroxetinee,f | 12.5 or 25 mg | Depressive and vasomotor |
| Sertralineg | 100 mg | Depressive and vasomotor |
| Other antidepressants | ||
| Duloxetineh | 60 to 120 mg | Depressive and vasomotor |
| Venlafaxinei | 75 to 225 mg | Depressive and vasomotor |
| Mirtazapinej | 30 to 60 mg | Severe depressive symptoms; used as an adjunct to estrogen |
| Hypnotics | ||
| Eszopiclonek | 3 mg | Depressive and vasomotor; insomnia |
| Zolpideml | 5 to 10 mg | Insomnia |
| Anticonvulsant | ||
| Gabapentinm | 300 to 900 mg | Vasomotor |
| SSRIs: selective serotonin reuptake inhibitors | ||
| Source: Reference Citations | ||
Nonpharmacologic interventions are viable options for women who are reluctant to begin HRT or psychotropics.
Psychotherapy. Interpersonal psychotherapy (IPT) and cognitive-behavioral therapy (CBT) have been recommended to address psychosocial elements of perimenopausal mood lability.21 For women with climacteric depression, IPT focuses on role transitions, loss, and interpersonal support, whereas CBT focuses on identifying and altering negative thoughts and beliefs.
