Females in their 40s and 50s often present to their primary care providers with new-onset depressive symptoms. It can be difficult to assess if the symptoms are part of menopause/perimenopause or if they represent a new onset depressive disorder. One complicating factor is that menopause can independently increase the risk of onset of a depressive episode even in women without a history of depression. Given this, it is important for primary care providers to be comfortable with conducting an appropriate assessment of symptoms to determine a diagnosis and an appropriate treatment plan.
During the assessment, it is important to ask a thorough menstrual history as well as ask if the patient is experiencing other physical symptoms of menopause. The menstrual history should include if her cycle is regular or irregular, the heaviness of the flow, and when she had her last menses. Perimenopause begins when the cycle begins to vary and ends 12 months after the last menses. If it is clinically unclear if a patient is in perimenopause, one can measure FSH and estrogen levels during the early follicular phase to confirm perimenopause. During perimenopause, vasomotor symptoms (VMS) and mood lability may worsen. VMS includes hot flashes and night sweats. Other physical symptoms of menopause include: forgetfulness, insomnia, sexual changes (decreased desire, vaginal atrophy), joint pains, bladder discomfort, breast pain, and headaches. Patients with VMS are more likely to have mood symptoms associated with menopause, which can include: irritability, mood lability, and anxiety. Both the mood changes associated with menopause as well as VMS are linked to dysregulation of monoaminergic neurotransmitter systems caused by fluctuating estrogen levels.
Treatment is based on if the patient is in perimenopause and the severity of the mood symptoms. The other factor is the appropriateness of hormone replacement therapy (HRT). While there has been much controversy about HRT since the Women’s Health Initiative study in 2002 showed concerns about possible increased risk of breast cancer and limited cardiac protection of HRT, more recent evaluation of the study results has reduced many of these concerns.
As a result estrogen is the only FDA approved treatment for VMS, and since mood symptoms of menopause are so intimately linked to VMS, theoretically estrogen would be a good treatment for depression linked to menopause as well. If the patient is in perimenopause and HRT is an option, studies have shown that HRT can be helpful for both the mood symptoms of perimenopause as well as VMS, so it can be an appropriate treatment for women presenting with mild-moderate mood symptoms related to perimenopause. If HRT is not an option or if the mood symptoms are more severe, treatment with an antidepressant is an option.
Studies have shown that the selective norepinephrine reuptake inhibitors (venlafaxine, duloxetine) are more helpful for VMS than the serotonin reuptake inhibitors, so if HRT is not an option, one might consider starting with an SNRI to treat both the mood symptoms as well as the VMS. If HRT is an option, one might consider a combination of HRT and an SSRI as an alternative approach. If the patient is not clearly in perimenopause, then treatment should proceed as usual, with the SSRIs being the first like agents for moderate-severe depression. Of course, for all patients, adjunctive supportive or cognitive-behavioral therapy should be strongly considered.