Phase 2 Clinical Trial Examines the Efficacy of a Novel Psychedelic for the Treatment of Postpartum Depression

Over the last few years, we have seen several novel, rapidly acting antidepressants developed and for the treatment of PPD: brexanolone and zuranolone. And now another novel treatment – RE104 – is being developed for the treatment of postpartum depression (PPD) by Reunion Neuroscience.

Participants are now being enrolled in RECONNECT, a Phase 2 clinical trial of RE104 for the treatment of postpartum depression (PPD). RE104 is a novel treatment, a prodrug of 4-OH-DiPT, which is a synthetic compound similar in structure to psilocin, a psychedelic compound found in “magic mushrooms”. The main advantage of the RE104 is that it delivers a psychedelic experience of a shorter duration compared to other psychedelics like psilocybin. According to Reunion Neuroscience, data from a Phase 1 clinical trial indicated that RE104 produced a “psychedelic state similar in intensity and quality to psilocybin, but lasting only about half the time (3 to 4 hours)”.

For the RECONNECT study, eligible participants must be within 12 months postpartum and must meet DSM-5 criteria for a postpartum major depressive episode (onset during the last trimester of pregnancy or within 4 weeks of delivery) of moderate to severe severity (HAM-D of 24 or greater). The study excludes individuals with certain psychiatric conditions (including history of postpartum psychosis and current treatment-resistant depression), significant suicide risk, or prior psychedelic use. During the course of the study, depression severity will be assessed at days 1, 7, 14, and 28.

Participants in the RECONNECT trial are required to stop breastfeeding either before or at the time of screening to prevent any potential drug transfer to the infant through breast milk. (The study protocol does not mention whether or not breastfeeding can be resumed at any point after administration of the drug.) 

In this double-blind randomized controlled trial, participants receive a single 30 mg subcutaneous dose of RE104, while the comparator group receives a 1.5 mg dose. Participants are not required to be hospitalized for the duration of the trial. The trial includes a preparation session before the first dose and two integration sessions after receiving the medication.

Stay tuned…

Ruta Nonacs, MD PhD

References

Reunion Neuroscience Inc. announces first patient dosed in phase 2 clinical trial of RE104 for the treatment of postpartum depression. Reunion Neuroscience. July 23, 2024.