Evaluation And Treatment Of Perimenopausal Depression

Publication Date: February 14, 2019
Last Updated: March 14, 2022



  • The perimenopause is a window of vulnerability for the development of both depressive symptoms and major depressive episodes.

  • The risk of depressive symptoms is elevated during the perimenopause even in women with no history of major depressive disorder.

  • Most midlife women who experience a MDE during the perimenopause have experienced a prior episode of depression; therefore, the episode represents recurrence of their illness. First lifetime onset of MDD during this time is less common.

  • Data are mixed about whether women who undergo surgical menopause are at increased or decreased risk for developing depression compared with women who transition through menopause naturally. However, recent large-scale studies show an elevated risk of depression in women following hysterectomy with and without oophorectomy. Women with primary ovarian insufficiency also have shown elevated rates of depression.

  • Risk factors for depressive symptoms during the perimenopause include prior MDD, sociodemographic factors (e.g., younger age, black race, financial difficulties), psychosocial factors (adverse life events, low social support), menopause symptoms (VMS, sleep disturbance), anxiety symptoms, and reproductive-related mood disturbance (e.g., postpartum and/or premenstrual depressive symptoms).

  • Risk factors for MDD during the perimenopause include mental health factors (prior MDD, current use of antidepressants, anxiety, trait anxiety, premenstrual depressive symptoms), sociodemographic factors (black race, high BMI, younger age), psychosocial factors (upsetting life events, social isolation), and menopausal symptoms (especially sleep disturbance).


Clinical presentation

  • Depression during midlife presents with classic depressive symptoms, commonly in combination with menopause-specific symptoms (i.e., VMS, sleep disturbance) and psychosocial challenges.

  • Several common symptoms of the perimenopause (hot flashes, night sweats, sleep and sexual disturbances, weight/energy changes, cognitive shifts) complicate, co-occur, and overlap with the presentation of depression during this stage.

  • Vasomotor symptoms are associated with depressive symptoms but not MDEs, except in women with first lifetime onset of a depressive episode during the perimenopause.

  • Life stressors that are common for women at midlife (e.g., caring for children and parents, career and relationship shifts, aging, body changes) and personal/family illness can adversely affect mood but “empty nest” and “revolving door” have little enduring effect.


Assessment and diagnosis

  • Evaluation includes identification of menopause stage, assessment of co-occurring and overlapping menopause and psychiatric symptoms, consideration of psychosocial risk factors, appreciation of the differential diagnosis, and use of scales to aid in disentangling symptoms and distinguishing diagnoses.

  • Women with past MDEs (not necessarily hormone related) and women with severe depressive symptoms and/or suicidal ideation should always be evaluated for a mood disorder.

  • The differential diagnosis of depression during the perimenopause includes MDD, subsyndromal depression, adjustment disorder, psychological distress, bereavement, depressive episodes associated with bipolar disorder, and general medical causes of depression.

  • A menopause-specific mood-disorder scale does not exist; however, several general validated screening measures (e.g., PHQ-9) may be used for categorical determination of mood disorder diagnoses. Validated menopause symptom and health-related quality of life scales (e.g., MRS, MENQOL, Greene Climacteric Scale, Utian Quality-of-Life Scale) include mood items and may be useful in clarifying the contribution of menopause-related symptoms.


Treatment of MDD with antidepressants and psychotherapy

  • Proven therapeutic options for depression (i.e., antidepressants, CBT, and other psychotherapies) should remain as front-line antidepressant treatments for MDEs during the perimenopause.

  • Existing data on various SSRI and SNRI antidepressants (including citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine) suggest good efficacy and tolerability at usual doses. In women with a history of MDD, a prior adequate response to a particular antidepressant should guide treatment selection when MDD recurs during midlife years. Only desvenlafaxine has been studied and proven efficacious in large randomized placebo-controlled trials of well-defined peri-and postmenopausal depressed women.

  • Selection of antidepressants during the perimenopause should consider the woman's prior antidepressant trials and responses, available data on efficacy and tolerability in this specific population, management of challenging adverse effects (e.g., sexual dysfunction, weight changes) and safety (e.g., drug-drug interactions), given the likelihood of concomitant use of other medications during this stage of life.

  • In addition to their efficacy in treating MDD, many antidepressants (SSRIs and SNRIs) also improve menopause-related complaints (e.g., VMS, pain).

  • Clinicians should also consider treating co-occurring sleep disturbance and night sweats as part of treatment for menopause-related depression.


Estrogen therapy

  • There is some evidence that ET has antidepressant effects of similar magnitude to that observed with classic antidepressant agents when administered to depressed perimenopausal women with or without concomitant VMS.

  • Estrogen therapy is ineffective as a treatment for depressive disorders in postmenopausal women. Such evidence suggests a possible window of opportunity for the effective use of ET for the management of depressive disorders during the perimenopause.

  • There is some evidence that ET enhances mood and improves well-being in non-depressed perimenopausal women.

  • Hormonal contraceptives—particularly when used continuously—have shown some benefits for mood regulation and may improve depressive symptoms in women approaching menopause.

  • Transdermal estradiol with intermittent micronized progesterone may prevent the onset of depressive symptoms in euthymic perimenopausal women, but the evidence is not sufficient to recommend estrogen-based therapies for preventing depression in asymptomatic peri- or postmenopausal women and the risks and benefits must be weighed.

  • Estrogen-based therapies may augment clinical response to antidepressants in midlife and older women but their use should be considered with caution (i.e., preferably when also indicated for other concurrent conditions such as VMS).

  • Most studies on HT for the treatment of depression examined the effects of unopposed estrogen. Data on combined HT (estrogen plus progestogen) or for different progestogens are sparse and inconclusive.

  • Estrogen is not FDA approved to treat mood disturbance.


Alternative therapies

  • The available evidence is insufficient for recommending any botanical or complementary/alternative approaches for treating depression related to the perimenopause.

  • It is reasonable to recommend exercise in peri- and postmenopausal women with depression, particularly when used in combination with recommended psychotherapies and pharmacotherapies.


Recommendation Grading



Evaluation And Treatment Of Perimenopausal Depression

Authoring Organization

Publication Month/Year

February 14, 2019

Last Updated Month/Year

January 29, 2024

Supplemental Implementation Tools

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Diagnosis, Management, Treatment

Diseases/Conditions (MeSH)

D003863 - Depression, D047648 - Perimenopause


exercise, antidepressants, Antidepressants, hormone therapy, menopausal depression, psychotherapy, estrogen therapy