Sheryl Kingsberg, PhD: Psychedelic RE104 for postpartum depression

Reunion Neuroscience recently announced the initiation to enroll patients in the company’s phase 2 RECONNECT trial: a phase 2, multicenter, randomized, double-blind, parallel-group clinical study assessing the efficacy and safety of investigative drug RE104 for the treatment of postpartum depression.

RE104 is a 4-OH-DiPT prodrug synthetic product with psychedelic properties designed to provide a controlled, shortened experience to that of psilocybins.

Investigators including Sheryl Kingsberg, PhD, chief of the division of behavioral medicine, department of OB/GYN, University Hospitals Cleveland Medical Center, are assessing it in RECONNECT for outcomes including change in total 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 7 in treated patients versus control; change in total MADRS score from baseline to days 1, 14, and 28, as well as rate of patients with ≥50% reduction in depressive symptoms per MADRS; and rate of patients to achieve remission (MADRS scores of ≤10). Safety and tolerability outcomes will additionally be assessed through the trial.

In an interview series with Contemporary OB/GYN, Kingsberg discussed the RECONNECT trial, the current burdens of postpartum depression in the US and unmet needs in care for patients, and what makes RE104 an exciting and promising prospect for the condition.

Kingsberg’s interview is broken into 4 segments, as displayed in the video playlist above and in the navigable list below:

• The Prevalence and Effect of Postpartum Depression
• RE104 and Psychedelics for Psychiatry
• What the RECONNECT Trial Aims to Address in Postpartum Depression
• Setting Postpartum Depression Treatments Up for Success

Here are some of Kingsberg’s key perspectives on RE104, RECONNECT, and postpartum depression:

On the effect of postpartum depression

Postpartum mood disorders includes the 'blues', which would be anywhere from 50 - 80% of women who are going to experience the blues. That is not a clinical mood disorder. It is usually experienced as mood labelity, which would mean tearfulness or mood swings, if you will, where women will often say, 'I don't really know why I'm crying, but I just feel sad or anxious.' And that really does dissipate within a week or 2 after delivery.

Postpartum depression, which affects about 10 - 20% of women postpartum, has really 2 flavors, if you will. There is an anxious depression and there is a flat depression. Anxious looks very similar to obsessive, compulsive symptoms. There's a lot of catastrophic worry, or what I would put as 'what if' thinking that tends to be, evolutionarily, a tendency to protect. But it's often worries about, 'What if I'm not a good mother? What if I do something to my baby? What if something terrible happens to my baby?' And many women worry, 'Does that mean that I'm actually psychotic?' And that actually is not the case. The women who tend to worry, 'What if I do become crazy?' are not at risk to become psychotic. And the rates of that are very low: 1 - 2 per 1000. So, postpartum depression is very common, the blues are really common and postpartum psychosis, fortunately, is not common at all

On the potential benefit of RE104 in postpartum depression

For women with postpartum depression, many of them have never had a mood disorder before. Many have, but many have not. And this is a time where they've had a wanted pregnancy, now they have a baby, and this allows them a one-and-done treatment—essentially an afternoon of treatment that would allow them to return to breastfeeding very quickly, because the RE104 would be out of the system relatively quickly. What the FDA determines is yet to be seen, but it would be very quick. And so, many women have been hesitant about going on SSRIs or SNRIs or using other medicines, because they've been essentially forced to have to give up breastfeeding. So, this would allow for that, and again, would quickly give them relief, within essentially 24 hours.

On the need for timely, complementary care in postpartum depression

I mean, the basics of self-care including sleep and physical care are important, but please: I implore clinicians and women themselves not to underestimate the impact of postpartum depression. It is a medical condition. It is not just about sleep deprivation, although that can exacerbate it and women should seek help if they are struggling. You know, many women are ashamed. For example: this was a wanted pregnancy, and now they feel guilty or ashamed. 'Why am I feeling this way?' And so, to give a wakeup call to say this is real and can be treated, and now we are looking at even more options, I hope will encourage women to seek help and for clinicians to ask. I see lots of referrals from pediatricians, by the way, because many women don't actually see their obstetrician until maybe their 6-week visit if they get there. And so, oftentimes the referral comes from the pediatrician who sees the mom with her baby. So, I ask everybody who's out there who sees new moms, please ask.

On the future development of the RECONNECT trial

I think it's exciting. I am hoping that this phase 2 trial will enroll quickly, and then we can actually look at the data and see if we can show clinical efficacy, and then move on to a much larger trial. I think that it will offer an excellent option for women and their clinicians in shared decision making, to think about what options they want to think about when treating postpartum depression.

Patients with PPD, as well as clinicians who may have eligible and interested patients, can enroll in the RECONNECT trial here.