Can Ketamine Help Save New Moms?

The promise of ketamine for postpartum depression - is it empty without evidence, equity, and empathy?

⚠️ Content Note: This post discusses postpartum depression, suicide, and maternal mental health.

My curiosity about psychedelics for postpartum depression (PPD) began on a boat.

Last summer, I was cruising Lake Washington with a labor & delivery nurse. Between sun and small talk, she dropped a staggering insight: One in three pregnant women she intakes is already diagnosed with clinical depression. Most are in treatment, yet she wondered—what if microdosing psilocybin could help?

It wasn’t just a passing question. It was a frontline observation. And it reminded me why my work has always lived at the edge of systems—where women's needs meet outdated solutions.

Why Postpartum Depression Can’t Wait

One in eight new moms in the U.S. experiences PPD, yet nearly half go untreated.¹
According to the CDC, each week of a baby’s first year increases a mother’s risk of screening positive for depression.²
Suicide has now emerged as a leading cause of maternal death.³

When you look at the numbers, it's impossible not to ask:
How are we still failing new mothers?
And—inevitably—their babies, too.

Untreated PPD Changes Children’s Lives, Too

PPD isn’t just hard—it’s harmful. When untreated, the effects ripple into a child’s long-term development:

• Children of mothers with persistent PPD are more likely to face behavioral problems, academic struggles, and emotional regulation issues.⁹

• Maternal depression can rewire a child’s stress response, raising their risk for future mental health conditions.¹⁰

• One longitudinal study linked untreated PPD to adverse outcomes even years later.¹¹

Early intervention doesn’t just save moms. It protects future generations.

Why Aren’t We Asking the Right Questions?

Despite the known risks, most mothers are not regularly screened for mental health issues after birth:

• Only ~50% of new moms are screened for depression at all—and often just once, around the 6-week postpartum OB visit.⁴

• A 2020 JAMA Psychiatry study found most PPD cases emerge between 2–6 months postpartum—after that 6-week visit has passed.

• The American College of Obstetricians and Gynecologists now recommends ongoing support through the first 12 weeks, but adoption of this “fourth trimester” model has been inconsistent—especially for uninsured or under-resourced mothers.⁴ ¹³

The result? Many women are left to suffer silently, never asked the questions that might save their lives.

Why Current Interventions Fall Short

Traditional PPD treatments take time new mothers don’t have:

• Antidepressants: 2–4 weeks for relief

• Hormone replacement therapy: About 2 weeks

• Psychotherapy: 6–12 sessions (~10 weeks)⁴

All while babies cry, milk leaks, partners return to work, and the fourth trimester wears on.

Could Ketamine Be the Fast-Acting Answer?

Unlike psilocybin, which remains a Schedule 1 drug alongside LSD and heroin, ketamine is a Schedule 3 substance—FDA-approved, hospital-available, and on the WHO’s list of essential medicines. It's safe enough for children and animals and, crucially, fast-acting.

Why might it work for PPD?

Research suggests PPD is partly rooted in a disruption of the brain’s GABAergic system, responsible for calming and regulating mood.⁷ After birth, if GABA doesn’t “reset,” women can be left vulnerable to anxiety and depression.

Ketamine indirectly boosts GABA activity.⁸ That may explain why its antidepressant effects can be felt within hours—not weeks.

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Ep. 55 | A Doctor Answers, “How Does Ketamine Affect the Brain?”

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A Game-Changer in One Hour?

A recent clinical trial showed that a single, low dose of esketamine (a ketamine derivative) administered right after birth reduced PPD symptoms within one hour.⁵
Mothers who received a placebo were four times more likely to develop major postpartum depression than those who received ketamine.⁵

And unlike many psychedelic therapies, ketamine is already legally accessible in hospitals and birthing centers.

So what’s the catch?

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Ep. 54 | My Opinion on How Long Does Ketamine Work for Depression & My Experience

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The Access Gap—and the Insurance Catch-22

Despite promising research, ketamine for PPD is still considered experimental and investigational.

That means:

• No insurance coverage for this diagnosis

• Spravato (the only FDA-approved nasal spray) isn’t approved for PPD

• IV treatments can cost $3,600+ for six sessions—paid out-of-pocket

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Ep. 56 | Different Types of Ketamine-Assisted Psychotherapy

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What About Breastfeeding?

Safety concerns are valid. But here’s what we know:

• A 2022 study found ketamine and its active metabolites appear in breast milk at very low levels and decline rapidly.⁶

• The relative infant dose (RID) was less than 1%—well below the 10% safety threshold.⁶

• No adverse effects were observed in infants.⁶

• Most protocols recommend pausing breastfeeding for 6–12 hours post-dose.

Important caveat: this data comes from just four lactating women. More research is urgently needed.

Who’s Most at Risk?

Some women are more likely to experience PPD, especially those with:

• Personal or family history of depression or anxiety

• High stress during pregnancy (financial strain, trauma, lack of support)

• Complications during birth (emergency C-section, NICU stays)

• Hormonal imbalances

• Previous trauma (childhood abuse, intimate partner violence)

• Substance use during or before pregnancy

One study showed prenatal depression is the strongest predictor of postpartum depression.¹²

And yet? Maternal mental health screening remains inconsistent and underprioritized.

What Happens Next?

Returning to that nurse on the lake—she sees these women every day. She knows many will keep suffering after birth. And their suffering will be multiplied.

In harm reduction, we ask: Which risk is greater—the known devastation of untreated PPD, or the emerging risks of new treatments like ketamine?

Then we ask more complicated questions:

• How do we ask exhausted moms to travel to a clinic—without childcare?

• How many can afford $3,600 out-of-pocket?

• Can we trust venture-backed clinics to provide safe care to this vulnerable group?

• Will our healthcare system evolve to meet mothers’ real, urgent needs?

• What does informed consent look like when the science is still evolving?

We know PPD is life-threatening and life-altering.
We have early—but compelling—evidence that ketamine might help.

What we don’t yet have is a system designed to deliver that care equitably and responsibly.

Moms deserve better.
Babies deserve the best.

Stay curious,
April

Considering ketamine? Begin your research with SetSet’s clinician-created guide here.

🧠 Sources

1. CDC. Four in 5 pregnancy-related deaths in the U.S. are preventable (2022)

2. CDC. Four in 5 pregnancy-related deaths in the U.S. are preventable (2022)

3. NIH. Suicide and Maternal Mortality (2022)

4. Gavin NI, Gaynes BN, et al. Perinatal depression: a systematic review. Obstet Gynecol. (2005)

5. BMJ. Esketamine after childbirth for mothers with prenatal depression (2024)

6. Journal of Psychoactive Drugs. Ketamine in the Breast Milk of Lactating Women (2022)

7. Neurobiology of Depression. The GABAergic system and PPD (2020)

8. Harvard Health. Ketamine for treatment-resistant depression (2020)

9. Pharmacy Times. PPD and Its Long-Term Effects on Children (2018)

10. PMC. Maternal depression and child development (2009)

11. ScienceDirect. Persistent PPD and child development (2022)

12. Gavin NI, Gaynes BN, et al. Perinatal depression: prevalence & incidence (2005)

13. ACOG Committee Opinion No. 736. Optimizing Postpartum Care (2018)

14. JAMA Psychiatry. Timing and Persistence of Postpartum Depression (2020)

15. USPSTF. Recommendation Statement on Depression in Adults, Including Pregnant and Postpartum Women (2016)