Perimenopausal Depression

Primer

Perimenopausal Depression (also known as Major Depressive Disorder with peripartum onset in the DSM-5) is a subtype of depression experienced by women during the perimenopausal period, defined as the interval when a women’s menstrual cycles become irregular, usually between ages of 45 and 49.

Definition
  • The transition to menopause (or perimenopause, the beginning of ovarian failure) begins when menstrual cycles become 7 days longer or shorter than usual and extends to the early postmenopausal years.[1]
  • Menopause is defined as 12 months of amenorrhea following the final menstrual cycle, which usually occurs at an average age of 51 years.[2]
Epidemiology
Prognosis
  • The perimenopause period is a time of increased risk for depression compared to the premenopausal years
  • This period is also associated with perimenopausal symptoms, including hot flashes, night sweats, decreased libido, vaginal dryness, sleep disturbances, and memory complaints.[3]
    • Hot flashes and night sweats in particular are independent predictors of perimenopausal depression.
Comorbidity
Risk Factors
  • In women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. [4]

Pathophysiology

  • Since estrogen and serotonin may modulate hypothalamic thermoregulatory function, abrupt changes in neuromodulatory function and reproductive-hormone levels during menopause are thought to contribute to mood and vasomotor symptoms seen in menopause.

Treatment

Treatments for Perimenopausal Depression

MacQueen, G. M. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. The Canadian Journal of Psychiatry, 61(9), 588-603.
1st line Monotherapy: Desvenlafaxine, cognitive behavioural therapy
2nd line Monotherapy or Adjunctive therapy: Transdermal estradiol* (level 2)
Monotherapy: Citalopram, duloxetine, escitalopram, mirtazapine, quetiapine XR, venlafaxine XR (level 3)
Monotherapy: Omega-3, fluoxetine, nortriptyline, paroxetine, sertraline (level 4)
3rd line Monotherapy: Mindfulness-based CBT, supportive psychotherapy (level 4)
* = Women with an intact uterus should also be prescribed concomitant progesterone.

Hormonal

  • There is scant evidence to suggest that hormone replacement therapy should be used to prevent the onset of depressive symptoms during the menopause transition.[5]
    • Additionally, the U.S. Preventive Services Task Force recently found “no net benefit” of hormone therapy for primary prevention of most chronic disorders related to menopause, but they did find “convincing evidence” of risks like breast cancer, thromboembolism, and cardiovascular disease.[6]
  • However, there is evidence that transdermal estrogen therapy has antidepressant effects in diagnosed perimenopausal depression, especially in those with vasomotor symptoms.[7][8]
    • The risks and benefits of using hormonal therapy should be discussed with the patient prior to use.

Guidelines

Perimenopausal Depression Guidelines

Guideline Location Year PDF Website
Canadian Network for Mood and Anxiety Treatments (CANMAT) Canada 2016 - Link
North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers USA 2018 - Link

Resources

For Patients
For Providers
Articles
Research

References

1) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
2) Parry, B. L. (2008). Perimenopausal depression. American Journal of Psychiatry, 165(1), 23-27.
3) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
4) Cohen, L. S., Soares, C. N., Vitonis, A. F., Otto, M. W., & Harlow, B. L. (2006). Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Archives of general psychiatry, 63(4), 385-390.
5) Gordon, J. L., Rubinow, D. R., Eisenlohr-Moul, T. A., Xia, K., Schmidt, P. J., & Girdler, S. S. (2018). Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial. JAMA psychiatry.
6) Grossman, D. C., Curry, S. J., Owens, D. K., Barry, M. J., Davidson, K. W., Doubeni, C. A., ... & Landefeld, C. S. (2017). Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement. Jama, 318(22), 2224-2233.
7) Maki, P. M., Kornstein, S. G., Joffe, H., Bromberger, J. T., Freeman, E. W., Athappilly, G., ... & Soares, C. N. (2018). Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause, 25(10), 1069-1085.
8) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J. V., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. The Canadian Journal of Psychiatry, 61(9), 588-603.