Pharmacotherapeutic approaches to treating depression during the perimenopause

ABSTRACT

Introduction: Although postnatal depression is now well recognized, there is also a risk of depressive symptoms during perimenopause. The mechanisms underlying perimenopausal depression are still poorly understood; however, there are available treatment options.

Areas covered: This review describes: the current pharmacotherapeutic approaches for perimenopausal depression, their strengths and weakness, and provides recommendations on how current treatment can be improved in the future. An electronic search identified specific guidelines for the treatment of perimenopausal depression released in 2018, as well as recent clinical studies on the subject.

Expert opinion: The 2018 guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) as front-line medications for perimenopausal depression, but SSRIs and SNRIs are not always effective. The efficacy of estrogen in perimenopausal depression is well documented, but estrogen is not FDA-approved to treat mood disturbances in perimenopausal women. Clinical practice guidelines currently recommend to restrict hormone therapy to the symptomatic treatment of menopause (not for the prevention of chronic diseases). Research with new estrogenic compounds is under way to improve their benefit/risk ratio in perimenopausal depression.

KEYWORDS:

• Clinical trials
• guidelines
• menopausal transition
• oestrogen
• perimenopausal depression
• tibolone

Article highlights

• The risk of depressive symptoms is elevated during the perimenopause, particularly in women with a history of major depressive disorder (MDD).

• Recent, specific guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) as front-line medications for perimenopausal depression.

• SNRI and SSRI antidepressants often take weeks to months to exert their full therapeutic effects, leaving the risk of suicide and suicidal behavior unattended. Glutamate-based antidepressants are rapid-onset, sustained and potent antidepressants which deserve investigation in perimenopausal women with treatment-resistant depression (TRD), particularly as add-on therapy during SNRI or SSRI treatment initiation.

• A large number of studies demonstrated the efficacy of estrogen in perimenopausal and menopausal depression. Moreover, clinical practice guidelines currently recommend to restrict hormone therapy to the symptomatic treatment of menopause, but estrogen is not FDA-approved to treat mood disturbances in perimenopausal women. Current research with compounds acting either as agonists or antagonists in different tissues (SERM, selective estrogen receptor modulators) is underway, with the aim of improving the benefit/risk ratio in perimenopausal depression

• Perimenopausal depression may be associated to the stress and anxiety of psychosocial factors (death of partner, children leaving home, changes in marital status, caring for elderly parents, major life events, negative attitudes toward aging and menopause, low levels of social support and having few close friends). Cognitive behavioral therapy with or without an antidepressant could, therefore, be recommended to such patients.

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Acknowledgments

We are grateful to Monique Hazan-Naim (Craven, France) for providing information about perimenopausal depression in real-life.

Declaration of interest

RP Garay is the president of a non-profit association for therapeutic innovation (Craven, Villemoisson-sur-Orge, France). T Charpeaud declares consultant activities and has attended conferences on behalf of AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lundbeck, and Otsuka. He has also accepted invitations to congresses by Janssen, Lundbeck, and Otsuka and has participated in research projects with Amgen, Janssen, and Eli Lilly and Company. P Hannaert is an employee of the French CNRS. PM Llorca has received over the past 5 years research grants, fees for presentations at congresses or participation on scientific advisory boards from Allergan, Gedeon Richter, Gilead Sciences, Janssen, Eli Lilly and Company, Lundbeck, Otsuka, Recordati, Sanofi, Takeda, and Teva. S Logan declares having consulted for Bayer and having received speaker fees from Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.