Depression After Hormonal Contraception Initiation Linked to PPD

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In 2009, Jennifer Payne, M.D., and colleagues wrote an article in the Harvard Review of Psychiatry about the concept of reproductive depression, defined as depressive episodes that are triggered by reproductive hormonal changes. Payne and her colleagues analyzed several studies and argued that reproductive depression is a distinct clinical entity with specific treatment approaches separate from nonreproductive depression.

A study published in April in JAMA Psychiatry provides yet another example of a hormonal change that can trigger depression for individuals who are sensitive to such changes, said Payne, who was not an investigator on the study. Payne is a professor and vice chair of research in the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia and a member of APA’s Committee on Women’s Mental Health.

The JAMA Psychiatry study found that women who have a history of developing depression after initiating hormonal contraception may have a greater risk of developing postpartum depression. “This study provides evidence for the existence of a subgroup of women who are sensitive to hormonal transitions across the reproductive lifespan,” wrote Søren Vinther Larsen, M.D., a Ph.D. student at Copenhagen University Hospital, and colleagues.

Vinther Larsen and colleagues used health care data from Danish national registers and included all women born in Denmark after 1978 who delivered their first child between 1996 and 2017. Participants were excluded if they had a multiple birth or stillbirth, had never used hormonal contraception, or had a depressive episode before 1996 or within 12 months prior to delivery (as this could indicate an ongoing depression while entering pregnancy).

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The researchers identified participants who, prior to giving birth, experienced a depressive episode within six months of starting hormonal contraception. Depressive episodes were defined as filling a prescription for an antidepressant or being diagnosed with depression. They then identified the participants who developed postpartum depression, which they defined as filling a prescription for an antidepressant or being diagnosed with depression within six months after childbirth.

The study included 188,648 first-time mothers, of whom 5,722 (3%) had a history of depression associated with hormonal contraception initiation, and 18,431 (9.8%) had a history of depression that was not associated with hormonal contraception. Those with a history of depression associated with the use of hormonal contraception had a higher risk of developing postpartum depression than those whose past depressive episodes were not associated with hormonal contraception. Further, the risk of developing perinatal depression (including depressive episodes that occurred between the third trimester and six months postpartum) was also greater for participants who had a history of depression associated with hormonal contraception compared with those who did not.

The authors noted that, importantly, the findings do not imply that hormonal contraception use leads to a higher risk of postpartum depression. They instead indicate that a history of depression after initiating hormonal contraception may unmask susceptibility to postpartum depression and could be an important piece of a patient’s clinical history.

The study aligns with what Payne has found regarding reproductive depression generally. In 2013, she and her colleagues published a study in Neuropsychopharmacology in which they identified epigenetic biomarkers that can predict who is at risk of developing postpartum depression with 80% accuracy. She and her colleagues are continuing to study this work related to other types of reproductive depression, Payne said. She is optimistic that physicians may eventually be able to test to see who is at the greatest risk of reproductive depression, such as postpartum depression, and work on prevention before the symptoms even develop.

Some women are sensitive to reproductive depression (such as premenstrual dysphoric disorder or perimenopausal depression) for decades, from the onset of menstruation through menopause, Payne said.

“We are starting to see more attention being paid to postpartum depression, but I don’t think health professionals pay enough attention to other reproductive depressions that patients experience,” she said. “With more awareness about this, psychiatrists can better understand how their patients with depression may be impacted when they start oral contraception. It could be a rocky period, and they can be better prepared.”

The JAMA Psychiatry study was funded by grants from the Independent Research Fund Denmark. ■