SSRI Efficacy in Menopausal Women

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No wonder I couldn’t get out of bed last week. That selective serotonin reuptake inhibitor (SSRI) I’ve been using since 1993 to combat the depression I inherited from all the women on my mother’s side of the family, may slowly be losing its effectiveness.

In a classic case of women’s health research getting the short end of the stick, SSRI clinical trials originally excluded women because “researchers didn’t want to deal with the difficulties of controlling menstrual cycles,” according to Susan Kornstein, director of the Women’s Mental Health Institute at Virginia Commonwealth University.

Turns out that SSRIs work best in the presence of estradiol. Which could explain why 10mg daily dose of Prozac (the most prescribed SSRI in the world) worked for me in the past, but doesn’t seem to do the trick for me now that I’m menopausal.

A 2008 study published in the journal Psychoneuroendocrinology, found that the SSRI sertaline (Zoloft) had no effect on female rats that didn’t produce estradiol. The drug improved their depression-like symptoms, however, if accompanied by estradiol treatment.

The fact that SSRIs perform best in the presence of estradiol reveals the influence of estradiol on mental health, and suggests that, like men, menopausal women needing antidepressants should consider with their doctor whether an antidepressant that targets the neurotransmitters dopamine and norepinephrine, instead of serotonin, would be most effective.


Amy Roost’s passion is public health and policy. She earned a BA in political science from George Washington University and an MA in International Affairs from Columbia University in New York. Amy has worked as a press aide for Charles Percy, chairman of the U.S. Senate Foreign Relations Committee, and many non-profit organizations. She served as the Executive Director of the Chaparral Educational Foundation, the Del Mar Schools Foundation and The Thriver’s Network. In 2006, she founded Co-optimize, a business assisting independent bookstores across the country with various business services. She has spent the past several years developing and marketing the company’s proprietary software. Presently, Amy is moving in the direction of social entrepreneurship. As a blogger and marketing strategist, she hopes to speak for others whose voices are not yet being heard in the policy and research arenas.


  1. Studies have found that men respond better to antidepressants that target dopamine and norepinephrine instead of serotonin. These studies suggest men’s depression may have less to do with serotonin deficits than women’s depression.

  2. Wow, Amy. This is incredible information. Does this mean SSRIs are not very effective on men, either?

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