Antidepressants for Perimenopause: What the Evidence Supports

What antidepressants are used for perimenopause?

Antidepressants do work for depression in perimenopause. The 2019 joint NAMS and NNDC guideline names antidepressants and psychotherapy as the front-line treatments for depression during the menopausal transition, and several specific medicines have evidence behind them. Some also ease hot flashes. We use the same medicines for the anxiety that often travels with it.

Perimenopause is the stretch of years before your last period, when hormone levels swing and cycles turn irregular. Mood changes then are common enough that a task force of menopause and depression specialists wrote a guideline on them. In our practice the first thing we sort out is whether the mood change is the main problem or a symptom of something else. A good evaluation checks thyroid function and screens for bipolar disorder first, because both change the answer. Whether hormone therapy belongs in the plan is covered further down.

Why perimenopause raises the risk of depression and anxiety

In the Study of Women’s Health Across the Nation, reported in 2011, women were two to four times more likely to have a major depressive episode while they were perimenopausal or newly postmenopausal than when they were premenopausal. That held after accounting for prior depression, upsetting life events, hot flashes, and hormone levels. A separate study of women with no lifetime history of depression found a significant risk of a first episode during the transition.

Anxiety follows the same pattern, and in the women we see it often shows up first. What seems to matter is sensitivity to the swing in hormone levels rather than the levels themselves. That is why the risk held even after hormone levels were accounted for. Our perimenopausal mental health page covers why those shifts affect mood, and how to tell a rough patch in perimenopause from a depressive episode.

Which antidepressants have the strongest evidence in the menopausal transition

There is no single best antidepressant for menopause symptoms. The 2019 NAMS and NNDC guideline names seven antidepressants for menopause and the years before it, in two drug families, all of which work well. The one large head-to-head trial, in postmenopausal women, found no winner, so the choice is matched to you rather than picked off a list.

The two families are SSRIs and SNRIs. SSRIs, or selective serotonin reuptake inhibitors, raise the serotonin available between nerve cells. SNRIs are the serotonin-norepinephrine reuptake inhibitors. They act on norepinephrine as well.

One caveat matters more than the list. Only desvenlafaxine has been tested in two large randomized placebo-controlled trials in women whose menopausal stage was carefully defined, and the 2019 guideline says no other has, which does not make it the automatic pick. The evidence for the other six here is thinner, though all seven are well established for depression.

Two things usually decide, in our experience: how you responded to an antidepressant before, and which side effects you can least afford. Weight change and sexual side effects are the two that most often settle it. Name both out loud at the visit. If the first medicine falls short, switching to another is common, and NIMH treats needing a second attempt as routine.

What SSRIs and SNRIs do for hot flashes and night sweats

Several of them ease hot flashes and night sweats too. The same guideline reports that many SSRIs and SNRIs also improve menopause-related complaints, vasomotor symptoms among them. That is the clinical term for hot flashes and night sweats. It also tells clinicians to treat night sweats and broken sleep as part of treating the depression itself. A low-dose paroxetine capsule, at 7.5 mg, is FDA-approved, on a label last revised in 2013, for moderate to severe vasomotor symptoms, and that label notes the product is not an estrogen.

That product is approved for hot flashes only, and paroxetine is not one of the seven the guideline names for depression. Its label warns that paroxetine can make tamoxifen less effective, so tell your prescriber if you take tamoxifen. If low mood and night sweats are both bothering you, one medicine covering both is worth asking about. Your mood should still drive the choice.

Sleep deserves its own conversation, and not all the fixes are medicines. We cover sleep problems in perimenopause separately.

Which comes first, an antidepressant or hormone therapy?

When depression is the main problem, antidepressants and psychotherapy come first. The 2019 NAMS and NNDC guideline is direct: estrogen therapy is not approved to treat perimenopausal depression, though there is evidence it has antidepressant effects, most clearly in women who also have bothersome hot flashes.

Hormone therapy adds estrogen back, usually with a progestogen if you still have your uterus. In perimenopause the ovaries have not stopped; their output swings, which is part of why symptoms come and go. Estrogen alone has produced antidepressant effects in several trials of perimenopausal women, a meaningful finding, though not an approval to treat depression. Evidence for estrogen with a progestin is, in the guideline’s own words, sparse and inconclusive.

The two are not rivals. Plenty of women in our practice do best on both, with each prescriber handling their part and keeping the other informed, and where you start depends on which problem is bothering you most.

Will an antidepressant make me gain weight?

Some do and some do not, and the difference depends on the drug, not the family. A review in Obesity found that antidepressants carry varying risk of weight gain, with meaningful differences even between medicines in the same family. If weight matters to you, say so at the visit.

Two things get muddled here. Antidepressants are not weight-loss medications, and picking one is about treating the depression. Weight in midlife also moves for reasons that have nothing to do with a prescription, and depression itself pushes appetite and activity in both directions.

If weight is a priority, a prescriber can pick an option with a lower risk of gain. Have that conversation at the first visit, while the options are still open.

Who antidepressant treatment fits, and how to get evaluated in Pennsylvania

An antidepressant is worth discussing when depression or anxiety is moderate to severe, or when an antidepressant has helped you before. Raise it too if your mood and your hot flashes started the same year. An evaluation settles it.

Zellig Psychiatry is a Pennsylvania psychiatry practice. We see patients in person in Wayne and Perkasie and by secure video anywhere in the state, and we take nearly all commercial insurance. Care is led by physician assistants in psychiatry, including Riley Guinan, PA-C, in a collaborative practice that includes a psychiatrist. If you also see an OB/GYN, we write to them.

Four things make a first visit more useful:

• Every medication and supplement you take, including hormone therapy
• Any antidepressant you have tried, and what happened
• When your cycles changed, and when your mood did
• Which symptom you most want gone

Fees and booking sit on our medication management page.

Frequently asked questions

In a crisis, or if you are thinking about harming yourself, call or text 988 for the Suicide and Crisis Lifeline.

This page is general information, not medical advice for your situation. Decisions about starting, changing, or stopping a medication belong with your prescriber.