Drug pipeline
Single LSD dose shows rapid, durable depression relief
Clinical takeaway: If confirmed, a one-time dosing model could reshape how undertreated depression is managed. Confirmatory phase 3 data and an FDA decision are still pending.
Most antidepressants take weeks to work, require daily use, and leave fewer than a third of patients in remission. DT120, an orally disintegrating LSD tablet, was tested as a single supervised dose against placebo in adults with moderate-to-severe depression. Scores dropped rapidly and stayed down through three months. The findings are early topline results from one of two registrational studies.
The candidate beat placebo on every measured endpoint. At week 6, the primary endpoint, Montgomery-Åsberg Depression Rating Scale (MADRS) scores fell 8.1 points more with DT120 than placebo, a drop to roughly 22 from a baseline near 35 in the active group. Response and remission tracked the same way: 35% of patients on DT120 responded versus 7% on placebo, and 24% reached remission versus 3%. The separation occurred quickly. By week 1, the placebo-adjusted MADRS difference was 14.2 points, and it still held at 7.3 points by week 12.
Standard antidepressants typically show placebo-adjusted MADRS differences of roughly 2 to 4 points over 6 to 8 weeks, but they often take a longer period to show a full effect. But an 8.1-point placebo-adjusted difference is still large by that benchmark, roughly two to three times the typical drug-placebo gap. MADRS scores range from 0 to 60.
DT120 is one of several psychedelics moving toward FDA approval for a psychiatric indication, and a positive pivotal readout adds weight to the class. This topline data is from the first of two registrational MDD trials; a second adds a low-dose arm specifically to test whether the drug's perceptual effects are unblinding patients and inflating the result. Definium says it is advancing toward an FDA submission.
"Many patients with MDD aren't helped by existing treatments, often experiencing partial responses, frequent medication changes, and long-term side effects," said John Sonnenberg, PhD, the study’s principal investigator and a clinical psychologist at Northwestern University Feinberg School of Medicine. "Importantly, these results stand apart from existing treatments, representing a potentially new paradigm for the management of major depression."