Positive first-line results for psychedelic novel in MDD

An experimental psychedelic tryptamine combined with supportive care is associated with improvements in moderate to severe major depressive disorder (MDD), new research suggests.

The best results from a phase 2a study of SPL026 (N,N-dimethyltryptamine intravenous [DMT]) showed a 57 percent remission rate 3 months after participants received a single dose of the drug, the developer reports.

Small Pharma noted in a press release that this is the first placebo-controlled efficacy study of a short-acting psychedelic for depression completed to date.

Researchers reported significant improvement in symptoms of depression 2 weeks after dosing, which was the primary endpoint; and improvement persisted at week 12.

“We now have the first evidence that SPL026 DMT, combined with supportive care, may be effective for people suffering from major depressive disorder,” lead researcher David Erritzoe, MD, PhD, clinical psychiatrist at the Institute, said in a statement. ‘Imperial College, London, England.

“For patients who have the misfortune to experience little benefit from existing antidepressants, the potential for rapid and long-lasting relief from a single treatment, as shown in this study, is very promising,” Erritzoe added.

Results of the randomized trial

The double-stage, blinded, randomized, placebo-controlled phase 2a study included 34 patients with moderate to severe major depressive disorder. Those who were taking pharmacological antidepressant medications at baseline discontinued their medication prior to SPL026 administration.

Patients received either a placebo (n = 17) or active treatment (n = 17). The latter consisted of a short intravenous infusion of 21.5 mg of SPL026, resulting in a 20-30 minute psychedelic experience and supportive therapy.

The dose was selected based on an analysis of data from the company’s Phase 1 study in healthy volunteers.

Efficacy was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) to measure changes in MDD symptoms.

Two weeks after dosing, those receiving the new therapy showed a significant reduction in depressive symptoms, demonstrating a -7.4 point difference versus the placebo group in the MADRS score (P = .02).

Analysis of key secondary endpoints showed a rapid onset of antidepressant effect 1 week after dosing, with a statistically significant difference in MADRS score between the active group and the placebo group of -10.8 points (P = .002).

Next steps?

All participants were subsequently enrolled in an open-label phase of the study in which they received a single dose of SPL026 with supportive care. They were then followed up for another 12 weeks.

In the open-label phase, patients who received at least one active dose of SPL026 with supportive care reported sustained improvement in symptoms of depression.

No apparent difference in antidepressant effect was observed between a one- or two-dose regimen of SPL026.

“SPL026 with supportive care was shown to have a significant antidepressant effect that was rapid and sustained,” said Carol Routledge, PhD, chief medical and scientific officer at Small Pharma.

“The results are clinically meaningful and allow us to progress into an international multisite Phase 2b study in which we seek to further explore the efficacy and safety profile of SPL026 in a larger MDD patient population,” Routledge added.

Kelli Whitlock Burton is a Medscape Medical News reporter covering psychiatry and neurology.

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