Inhaled mebufotenin shows promise in treatment-resistant depression

Single-day treatment with GH001, a synthetic formulation of inhaled mebufotenin, has been shown to be well tolerated and yield substantial improvements in depressive symptoms in patients with treatment-resistant depression in a phase IIb trial.

Conducted at 16 sites across Europe, the trial consisted of a 7-day, randomized, double-blind, placebo-controlled phase and a 6-month open-label extension phase. Researchers enrolled adult patients with depression who had shown no response to 2–5 oral antidepressant treatments, with current episode duration of up to 2 years.

A total of 81 patients participated in the trial and were randomly assigned to receive an individualized dosing regimen of up to 3 escalating doses of GH001 (6, 12, and 18 mg) (n=40; mean age 41.6 years, 60 percent female) or a placebo individualized dosing regimen (n=41; mean age 43.9 years, 53.7 percent female). Treatment was administered on a single day.

The primary efficacy endpoint was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (range, 0–60, with higher scores indicating greater severity) between baseline and day 8. The secondary endpoint was remission (MADRS score ≤10) at day 8.

At day 8, MADRS score decreased significantly with GH001 vs placebo (least squares mean difference, −15.5; p<0.001; effect size, −2.0).

The percentage of patients who had achieved remission by day 8 was 57.5 percent with GH001. None of the patients who received placebo achieved remission.

There were no severe or serious adverse events documented during the placebo-controlled treatment phase.