Why doctors are studying new drugs to treat women’s midlife mood swings

Research is beginning to uncover a better understanding of the symptoms, but the science has yet to change the treatment that many women receive
Research is beginning to uncover a better understanding of the symptoms, but the science has yet to change the treatment that many women receive

Summary

Many women feel anxious or depressed during perimenopause. Researchers are looking at new ways to help

Researchers are testing several new drugs to treat depression and anxiety symptoms that women frequently experience during perimenopause, the years leading up to menopause.

Mood changes are a common symptom of perimenopause, a transition before the last menstrual period that typically begins during a woman’s 40s. As many as one-third of women experience depressive symptoms during this time, research has found.

Antidepressants are often prescribed to women for midlife depression, but the drugs don’t work for everyone and can have side effects. Some doctors say hormone therapy used for menopause symptoms can help, but women who have had breast cancer and other conditions aren’t advised to try that option.

Now scientists are studying medications that may help combat perimenopausal mood changes in different ways. Some of these drugs are already approved for other health issues. Doctors are also hopeful that some new drugs aimed at treating hot flashes may also help with mood changes.

Women are starting to seek more answers about perimenopause, an oft-neglected life stage that doctors receive little training on. Research is beginning to uncover a better understanding of the symptoms, but the science has yet to change the treatment that many women receive.

Perimenopause starts when a woman’s menstrual cycle becomes irregular. The transition can range from three years to more than a decade as fluctuating hormone levels can trigger hot flashes, night sweats and mood changes, among other symptoms.

Looking for options

Lori Kingsley, a 51-year-old in Seattle who has had breast cancer, has limited options for treating recent mood changes.

Ms. Kingsley used to fly planes, go skydiving and love traveling. But for the past year she has suffered severe panic attacks when she travels. She says her doctor attributes the newfound anxiety to hormone fluctuations that occur during perimenopause.

“I never associated mental concerns or issues with menopause, always more physical symptoms," says Ms. Kingsley.

Unable to try hormone therapy, she takes anti-anxiety medication as needed and has learned meditation and mindfulness techniques. The pills, which she usually takes a few days before traveling, bring her anxiety down a notch but don’t make it go away, she says.

She says she wishes she could try hormone therapy, which has been shown in several studies to help treat perimenopausal depression and anxiety, in addition to other perimenopause symptoms, like hot flashes and irritability.

“I would love to have something else," she says.

Testing other treatments

Most of these drugs are in the early stages of testing and far off from being approved for treating mood disorders in perimenopause.One is approved by the U.S. Food and Drug Administration for postpartum depression, and doctors sometimes prescribe drugs off-label if research indicates promise. At least one other medication is under FDA review for hot flash treatment. It might prove useful for mood changes, too.

One study is testing to see if brexanolone, an injectable drug used to treat postpartum depression, may help alleviate depression in perimenopausal women.

The drug, marketed under the brand name Zulresso and made by Sage Therapeutics, doesn’t contain estrogen, a hormone that can increase the risk of uterine cancer and cardiovascular disease. So while it may have an effect on mood, it wouldn’t have the potential negative side effects of estrogen, researchers say. The study is being led by Hadine Joffe,director of the women’s hormones and aging research program at Brigham and Women’s Hospital and professor of psychiatry in women’s health at Harvard Medical School.

Other researchers are studying Pfizer’s drug Duavee, which is FDA-approved for hot flashes and bone-density loss.

Duavee combines estrogen with a drug that can block the effect of estrogen on certain parts of the body while turning it on for others. The blocking may help the estrogen alleviate mood changes in the brain without raising the risk of cancer in other parts of the body, says Crystal Schiller, an associate director of behavior therapy and reproductive science in the Center for Women’s Mood Disorders at University of North Carolina School of Medicine, who is leading the research.

Pfizer voluntarily recalled Duavee in 2020 due to a packaging issue that the company is working to resolve, a spokesman says.Dr. Schiller says her preliminary data finds the drug works just as well as hormone therapy in managing mood changes during perimenopause. She is writing a pilot study for publication and says the drug had a “rapid antidepressant effect" similar to hormone therapy.

In a separate study, National Institutes of Health researchers are testing an experimental Lilly compound in women with past perimenopausal depression to see if two doses—one low and one high—can relieve the effects of reduced estrogen levels, whose fluctuations are believed to trigger symptoms of perimenopause.

Some drugs that have been tested for other menopausal symptoms may also help with mood, scientists say.

Pauline Maki, a professor of psychiatry, psychology and obstetrics/gynecology at the University of Illinois in Chicago, is on the advisory boards of two companies in the final stages of testing new treatments for hot flashes that involve targeting neurons that regulate body temperature, she says. The treatments appear to improve sleep; she is hopeful they may help with mood, too.

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