Clinical Summary
Clinical Summary: Inhaled Mebufotenin (GH001) for Adult Patients With Postpartum Depression: A Phase 2a Open-Label Clinical Trial
Postpartum depression can severely disrupt maternal functioning and infant well-being, yet standard treatments often take weeks to work and can be difficult to sustain. This study tests whether a single-day inhaled mebufotenin regimen can deliver same-day symptom relief in women with moderate-to-severe postpartum depression.
Design
This phase 2a, proof-of-concept, single-arm, open-label trial
N
10 patients
Population
female outpatients aged 18–45 years who met the Mini-International Neuropsychiatric Interview19 (v 7.0.2) diagnostic criteria for major depressive disorder with peripartum onset, were >4 weeks postpartum at dosing and ≤12 months postpartum at screening, and had a Montgomery-Asberg Depression Rating Scale (MADRS) total score of ≥28, reflecting moderate-to-severe depressive symptoms
Duration
The trial consisted of a screening period; a day 1 visit where eligibility was reconfirmed; a day 1 visit where patients received the study drug, GH001; a day 2 follow-up visit; and the end of trial visit on day 8
Key Findings
- The primary end point was met, with a mean (95% CI) reduction from baseline to day 8 of −35.4 points (−39.32 to −31.48) in MADRS total score with GH001 treatment (P<.0001), corresponding to an approximate 96% relative reduction from baseline.
- All patients (100%) achieved both response and remission at day 8, as well as at 2 hours postdose and on day 2.
- Maternal functioning improved, with BIMF total score increasing by a mean (SD) of 34.1 (16.10) points (n=8) at day 8, an approximate 56% improvement.
- Illness severity improved across time points, with mean (SD) change in CGI-S score from baseline to 2 hours postdose, day 2, and day 8 of −3.7 (0.82), −3.8 (0.79), and −3.8 (0.83), respectively.
- Thirteen TEAEs were observed in 8 of 10 patients (80.0%), and were mostly mild in severity (87.5%); only 1 patient reported a TEAE with moderate severity, and no TEAEs of flashbacks, serious TEAEs, or severe TEAEs were reported.
Clinical Bottom Line
In this 10-patient open-label trial, a single-day individualized inhaled GH001 regimen produced ultrarapid and large antidepressant effects in postpartum depression, with 100% response and remission through day 8 and no serious adverse events. The findings support GH001 as a potentially fast-acting outpatient intervention that now needs confirmation in randomized, placebo-controlled trials.
Practice Implications
- For patients with moderate-to-severe postpartum depression who need rapid symptom relief, GH001 showed clinically meaningful improvement by 2 hours postdose and maintained remission through day 8.
- This treatment approach was delivered in one supervised dosing day with all patients discharge-ready within the dosing day, supporting consideration of an outpatient workflow with postdose monitoring.
- Monitor for transient increases in blood pressure and heart rate after dosing, even though these spontaneously returned to baseline within 20–60 minutes after dosing and no clinically significant safety shifts were identified.
- When counseling lactating patients, discuss that mebufotenin levels in breast milk declined to below the limit of quantification (BLQ, 0.025 ng/mL) to 0.04 ng/mL ∼8 hours postdose, all levels were BLQ on days 2 and 8, and bufotenin was BLQ at all time points.
