Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations

SUMMARY: 

Perimenopause, or transitional menopause, is defined as the early transition stages into menopause as well as the early post-menopause stage. It is a particularly vulnerable time for depressive symptoms and major depressive episodes in women.  The following are the guidelines on evaluation and management of perimenopausal depression developed by NAMS in collaboration with the National Network of Depression Centers Women and Mood Disorders Task Group expert panel. The guidelines address an approach to depressive symptoms and depressive disorders in midlife women.  

KEY POINTS:

Epidemiology and Risk Factors  

Epidemiology 

  • Risk increased for both depressive symptoms and major depressive episodes (MDE) during the perimenopause  
  • Risk for depressive symptoms is elevated in the perimenopause even without previous history  

Risk Factors for Depressive Symptoms  

  • Prior Major Depressive Disorder (MDD) 
  • Reproductive-related mood disturbance  
    • Postpartum and/or premenstrual depressive symptoms 
  • Sociodemographic factors including  
    • Younger age | Black race | Financial difficulties 
  • Psychosocial factors   
    • Adverse life events | Low social support 
  • Anxiety symptoms 
  • Common midlife stressors  
  • Menopausal symptoms 
    • VMS | Sleep disturbance  

Risk factors for MDD 

  • Mental health factors  
    • Prior MDD | Current use of antidepressants | Anxiety | Premenstrual depressive symptoms  
    • Sociodemographic factors (e.g., black race, high BMI, younger age)  
    • Psychosocial factors (e.g., upsetting life events and social isolation)  
    • Menopausal symptoms (sleep disturbance) 
  • Limited and/or inconclusive data  
    • Data suggests increased risk following hysterectomy with and without oophorectomy | Premature Ovarian Failure 
    • Literature review can be found in the full open access guideline paper (‘Primary Sources – Learn More’ below)  

Assessment and Diagnosis 

The guidelines state  

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

Diagnostic Criteria (DSM-5)  

MDD aka ‘Depression’ 

  • Discrete episodes of Major Depressive Episodes (MDE) 
    • ≥2 weeks’ duration (most longer) with significant changes in at least 5 of the following  
    • Altered Affect (depressed mood) | Cognition | Impaired concentration  | Diminished interest in pleasure | Weight and appetite changes | Sleep disturbance | Restless or slowed down | Fatigue | Feeling worthless or guilty | Thoughts of death or suicidal ideation with or without a plan  
    • MDE must include either depressed mood or loss of interest in pleasure 
    • Symptoms are present every day throughout the episode  
  • Significant effect on daily living, including social and occupational interactions  
  • No other explanation for the situation (e.g., medical disorder, such as a stroke)  

Clinical assessment  

  • Determine the specific menopause stage 
  • Assess psychosocial risk factors and overlapping menopause and psychiatric symptoms 
  • Identify women with  
    • Past major depressive disorder  
    • Severe depressive symptoms  
    • Suicidal ideation  
  • Differential during menopausal transition includes  
    • MDD | Subsyndromal depression | Adjustment disorder | Psychological distress | Bereavement | Bipolar Depression | General medical causes of depression 
    • Most women who experience a MDE are likely experiencing a recurrence  

Note: Refer women with past MDEs and severe depressive symptoms for as professional evaluation for the presence of mood disorder 

Screening Tools 

  • There is no specific ‘menopause’ mood disorder screening tool  
  • There are a variety of validated general screening tools that can be used including  
    • PHQ-9 (see ‘Learn More – Primary Sources’ below)
  • To clarify contribution of menopause-related symptoms, consider the use of the following Quality of Life (QoL) tools  (see ‘Learn More – Primary Sources’ below)
    • Menopause Rating Scale (MRS) | Menopause-Specific Quality-of-Life Scale (MENQOL) | Greene Climacteric Scale | Utian Quality-of-Life Scale 

Treatment 

  • First line of treatment should include demonstrated therapeutic options for depression  
    • Antidepressants 
    • CBT  
    • Psychotherapy 

Antidepressants 

  • Desvenlafaxine has been studied in large RCTs that included postmenopausal depressed women and has proved to be effective 
  • Other SSRIs and SNRIs at regular doses are well tolerated and effective 
    • Citalopram | Duloxetine | Escitalopram | Fluoxetine | Sertraline | Venlafaxine 
    • Those used by patients successfully in past MDEs should be considered for first line treatment 
    • Some SSRIs and NSRIs also help with menopausal symptoms including hot flashes, night sweats and sleep disturbances 
  • Pay special attention to potential adverse effects in patients given the unique challenges of this population including  
    • Sexual dysfunction 
    • Weight changes  
    • Interactions with other medications 

Estrogen-Based Therapies (ET) 

  • Estrogen is not FDA approved to treat mood disturbance 
  • Consideration might be given for ET use specifically during the perimenopause 
    • Some evidence that ET has antidepressant effects in perimenopause but not postmenopause 
    • ET may enhance mood and well-being in non-depressed perimenopausal women  

ET used together to enhance antidepressants should be used with caution  

  • ‘Preferably’ in women who require treatment for vasomotor symptoms 
  • Data on combined estrogen and progestogen are sparse and inconclusive 
  • Hormonal contraceptives  
    • Used continuously, have shown some benefits for mood regulation for women approaching menopause 

Note: Studies on hormone therapy (HT) and depression focused on unopposed estrogen. Combined HT is not well studied and data is inconclusive  

Alternative (supplements and non-traditional) approaches 

  • Evidence is insufficient for recommending use at this time  

Exercise 

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

Learn More – Primary Sources:

NAMS: Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations

DSM-5 and mental disorders in older individuals: an overview 

Major depression

Diagnostic and Statistical Manual of Mental Disorders (DSM–5) 

PHQ-9 Screening Tool (University of Michigan)

Menopause Rating Scale (MRS): A methodological review  

NAMS: Utian Quality of Life Scale