July 29, 2025

You Asked: Can Zuranolone Be Used to Treat Postpartum Depression in a Mother with Bipolar Disorder?

Postpartum Psychiatric Disorders, Postpartum Psychiatric Disorders

While zuranolone may show promise for the treatment of depressive episodes in patients with bipolar disorder, more research is needed.

Ruta Nonacs, MD PhD

Zuranolone, marked as Zurzuvae, is a novel, oral neuroactive steroid and positive allosteric modulator of the GABA-A receptor, the main inhibitory neurotransmitter system in the brain. Unlike traditional antidepressants that primarily target serotonin or norepinephrine pathways and often require weeks to achieve effect, zuranolone is designed to work rapidly—frequently improving depressive symptoms within days.

Zuranolone was approved by the FDA for the treatment of postpartum depression (PPD); however, the initial clinical trials of zuranolone for PPD specifically excluded women with a history of bipolar disorder from participating. This exclusion was intended to focus on unipolar depression and to minimize safety risks, as the treatment needs and risks in patients with bipolar disorder differ significantly. Importantly, patients with bipolar disorder are at higher risk for treatment-emergent mania or mood instability when exposed to certain antidepressant medications.

Postpartum depression in women with histories of bipolar disorder is often severe and refractory to treatment. Many have wondered if zuranolone could be helpful in this setting. Although zuranolone has not been systematically studied in postpartum women with histories bipolar disorder, emerging evidence from studies in non-postpartum adults offers some early signals of efficacy and safety.

Open-Label Phase 2 Study in Non-Postpartum Adults with Bipolar Depression

A multi-center open-label phase 2 trial (presented as a poster at Psychiatric Congress 2020) investigated zuranolone in adults aged 18 to 65 with Bipolar I or II disorder, all of whom were experiencing a major depressive episode (MDE). The trial included patients who had a history of mania or hypomania, with a Hamilton Rating Scale for Depression (HAMD-17) score of at least 22 at baseline.

Participants received open-label zuranolone 30mg daily for two weeks, with follow-up to Day 42. Depression severity was measured using the HAMD-17 and Montgomery-Åsberg Depression Rating Scale (MADRS), as well as response rates (a ?50% reduction in HAMD-17 scores).

35 patients initiated zuranolone; 71% completed the full two-week course.
Common side effects (?5%): somnolence, headache, diarrhea, and sedation.
No cases of mania, serious adverse events, or medication discontinuation due to adverse effects were reported. However, two patients reported hypomania.
Efficacy: At Day 15, mean MADRS improved by 15.5 points and HAMD-17 by 11.4 points; improvements were sustained at Day 42.
Response Rates: 45% at Day 15, 50% at Day 42.

These results suggest zuranolone may be potentially effective for depressive episodes in bipolar disorder, although further studies—including controlled trials—are needed.

Anecdotal Reports: Zuranolone in Mothers With Bipolar Depression

Several case reports add to our understanding, although it must be emphasized that such anecdotal evidence does not replace large-scale clinical studies.

Case 1: A 30-year-old mother with bipolar II disorder, well-managed on lamotrigine, sertraline, and low-dose risperidone, experienced postpartum depression and obsessive-compulsive symptoms during her third trimester. Zuranolone (50mg) was added at 10 months postpartum while she continued breastfeeding. She reported a dramatic improvement in mood and OCD by day 14, with no sedation in her or her nursing infant. Over the next 8 months, she remained stable and was able to taper off risperidone.
Case 2: A 38-year-old woman with bipolar I disorder and prior psychosis developed severe postpartum depression with suicidal ideation after a miscarriage at 4 months gestation. Zuranolone 30mg was added to her stable regimen of olanzapine and fluoxetine, resulting in rapid resolution of depression and suicidality within 24 hours. She remained stable for over a year after treatment.

Bottom Line

Bipolar depression after childbirth is both common and very challenging to treat. There is a clear unmet need for effective, fast-acting, and safe interventions in this population.

It is reassuring that in the phase 2 trial described above (in non-postpartum adults), no participants experienced worsening mood or mania. However, due to the absence of clinical trial data in postpartum women with bipolar disorder, any off-label use of zuranolone in this setting should be approached with caution.

Based on his clinical experience, Price endorses the use of zuranolone in postpartum patients with bipolar disorder. As is the case in non-postpartum patients, he recommends ensuring adequate and ongoing treatment with a mood stabilizer (such as lithium, lamotrigine, or antipsychotics) before introducing new adjunctive therapies for depression.

While zuranolone may show promise for the treatment of depressive episodes in patients with bipolar disorder and may ultimately offer a new option for mothers with postpartum depression and histories of bipolar disorder, more research is needed—especially in postpartum populations—to fully determine the safety and efficacy of zuranolone in this setting. For now, treatment with zuranolone is indicated only in women with postpartum depression and no history of bipolar disorder.

Ruta Nonacs, MD PhD