Shortly after giving birth, a combination of plummeting hormones and the exhaustion of new motherhood can cause a surge of negative emotions. Meanwhile, the brain’s prefrontal cortex has difficulty regulating the emotions, creating a cocktail for postpartum depression.

Most treatments for the condition are pharmaceuticals, but many patients will not take drugs while breastfeeding, and people who are on antidepressants often stop as soon as they become pregnant. Only one alternative is currently available, usually cognitive behavioral therapy or interpersonal psychotherapy.

But another option may become available in the next few years: A drug-free procedure that stimulates brain nerve cells with magnetic pulses, targeting parts of the brain associated with depression.

Repetitive transcranial magnetic stimulation is already approved by the FDA for major depressive disorder and treatment-resistant depression. Researchers hope it could trigger a “biological rest” for new moms.

“Having effective treatments for postpartum depression has incredible public health consequences for new moms, their children, and their families,” said Lee Cohen, MD, director of the Ammon-Pinizzotto Center for Women’s Mental Health at Mass General Hospital in Boston.

The modality is being tested in 192 women with postpartum depression who gave birth 6 or less months prior. The women will undergo 5 days of treatment for 1 week.

Developing treatments for postpartum depression was not a focus of research until about a decade ago, leaving women in need of more options, Cohen said.

“Although we have good safety data on pharmacological treatments for people with postpartum depression, some women do not want to take medication especially while breastfeeding,” said Simon Lucaj, MD, director of the Interventional Psychiatry Program at Montefiore Einstein, Albert Einstein College of Medicine in Bronx, New York.

Recent Developments

About 1 in 8 women who give birth in the US report symptoms of postpartum depression –– lingering feelings of intense sadness that make it difficult to bond with their babies. But the first FDA-approved drug for the condition only came in 2019, called brexanolone (Zulresso), which requires a 60-hour intravenous (IV) infusion. Four years later, the agency approved the first oral medication for postpartum depression, called zurzuvae (Zuranolone). Clinicians have also been able to safely prescribe sertraline (Zoloft) off label, Lucaj said.

Participants in the trial will remain on their current medications to prevent withdrawal symptoms and ensure that outcomes accurately reflect the efficacy of the treatment, said Martijn Figee, MD, PhD, director of the Mount Sinai Interventional Psychiatry Program, New York City, who is co-leading the trial.

A typical course of this stimulation for major depressive disorder entails treatment for 5 consecutive days a week for about 7 weeks. Clinical trials and real-world data have shown that the modality is effective in about 40% of these people.

In the trial of postpartum women, participants will undergo a condensed treatment over 5 consecutive days with 10, 10-minute sessions a day in an outpatient setting.

Over the course of the treatment, Figee and his colleagues will administer 90,000 magnetic pulses to the dorsolateral prefrontal cortex through a coil secured to the scalp.

“It’s a targeted circuit-level intervention that restores functional connectivity in networks that have become dysregulated in depression,” said André Brunoni, MD, PhD, chief of the Division of Interventional Psychiatry at UT Southwestern Medical Center in Dallas, who is not involved in the trial.

The stimulation will target a small region of the brain called Brodmann area 25, known as the “sadness center” and is activated when a person experiences loss or grief. Once those emotions are processed, the dorsolateral prefrontal cortex can shut off that part of the brain, Figee said.

During the postpartum period, this process becomes more difficult, Figee said.

“We need to help the prefrontal cortex to regulate this deeper part of the brain,” he said.

If the results of the trial, slated to stop collecting data in 2029, show the stimulation to be an effective treatment for postpartum depression, Figee and his team would apply for expanded FDA approval, potentially opening the door for insurance companies to cover the procedure. Still, access may remain a barrier, Cohen said.

“Who are the patients, even if it works, who are willing to go for 5 days in a row?” he said. “That is a big ask for a new mom.”

Access has been an ongoing criticism for the postpartum depression drug brexanolone, which costs nearly $40,000 for a single, 60-hour long course of IV treatment.

Cohen said, he would like to know how the treatment works for moms who have comorbid anxiety or obsessive compulsive disorder, which he said is common in his patients.

The modality “has not been studied widely in patients with high levels of anxiety. Having taken care of this population for decades, I think that question needs to be answered,” Cohen said.

Other teams are studying whether a similar method, transcranial direct current stimulation, used at home with a portable device, could be effective for depression during and after pregnancy. Figee said an at-home option could be even better for access.

“We are trying to facilitate easier access to these treatments so people don’t have to come into the office all day for 5 days,” he said.

Researchers are also exploring psychedelic-assisted therapy for postpartum depression, although recent research has suggested psilocybin may not be safe to use while breastfeeding.

If proven effective, the modality will likely not become the standard first-line treatment for postpartum depression but rather expand the number of options moms can choose from at a time when postpartum depression is receiving more recognition as a public health issue, Cohen said.

“I think that we are seeing some decrease in stigma and peoples’ willingness to get help and that’s a good thing,” he said.

Figee reported being a consultant for Abbott and Medtronic. Cohen and Brunoni reported having no disclosures. The clinical trial is being funded by the US Department of Defense.

Kaitlin Sullivan is a journalist living in Colorado.