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

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% 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 trial of a short-duration psychedelic for depression completed to date.

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

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“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,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

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

The dose was selected based on data analysis 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 novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

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

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

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

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

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

Small Pharma
Dr. Carol Routledge


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

A version of this article first appeared on Medscape.com.

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

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% 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 trial of a short-duration psychedelic for depression completed to date.

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

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“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,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

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

The dose was selected based on data analysis 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 novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

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

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

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

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

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

Small Pharma
Dr. Carol Routledge


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

A version of this article first appeared on Medscape.com.

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

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% 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 trial of a short-duration psychedelic for depression completed to date.

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

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“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,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

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

The dose was selected based on data analysis 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 novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

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

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

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

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

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

Small Pharma
Dr. Carol Routledge


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

A version of this article first appeared on Medscape.com.

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