An investigational N,N-dimethyltryptamine treatment — commonly known as the hallucinogen DMT — achieved the primary endpoint in a phase IIa trial for major depressive disorder (MDD), developer Small Pharma announced.
Paired with supportive therapy, a 21.5-mg infusion of the agent, dubbed SPL026, significantly reduced depressive symptoms by 7.4 points more than placebo (P=0.02) at 2 weeks after treatment when using the Montgomery-Asberg Depression Rating Scale (MADRS), for which a 1.6- to 1.9-point change from baseline is considered clinically important.
There was a quick onset of antidepressant effect seen as early as 1 week post-dose, marked by a 10.8-point greater MADRS score improvement than seen with placebo (P=0.002).
During an open-label part of the study, where placebo patients also received a single dose of SPL026, durable remission of symptoms (a MADRS score of 10 or less) were achieved in 43% of participants by week 1 post-dose and in 57% by week 12. In this group, the total average reduction in MADRS score was 10.6 points at week 1 and 15.4 points at week 12. At this later timepoint, half of the participants were considered responders to the single dose, defined as a 50% or greater reduction in MADRS score from baseline.
“The results are exciting for the field of psychiatry,” said lead investigator David Erritzoe, MD, PhD, MRCPsych, of Imperial College London, in a statement released by the developer. “We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD.”
“For patients who are unfortunate to experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising,” he added.
The trial included 34 patients with moderate or severe MDD who underwent a medication withdrawal period prior to SPL026 dosing.
In the first part of the trial, which involved a blinded, randomized, placebo-controlled phase, 17 patients were administered a single 21.5 mg IV dose. This triggered a “20- to 30-minute psychedelic experience,” according to Small Pharma. They were then compared with 17 patients who only received placebo with supportive therapy.
After this 2-week study period, all participants were enrolled in the open-label phase, which involved a second dose of the treatment with supportive therapy for the initial treatment group and a single dose of SPL026 for the placebo group. While the supportive therapy was not spelled out in the topline results or on the trial’s ClinicalTrials.gov listing, it was psychotherapy in the prior phase I study. Participants were later followed for another 12 weeks.
There was no difference in antidepressant effect between those who received one or two doses of the treatment.
SLP026 was safe and well-tolerated, according to the company, with no drug-related serious adverse events reported and no reports of suicidal thoughts. All adverse events were either mild or moderate, and about 80% resolved during the visit. No safety signals emerged with vital signs, electrocardiograms, or labs.