The Best Depression Drug Results Ever?
How Definium Therapeutics results change the game for psychedelic medicine and investment.
In December 2024, Definium Therapeutics started a Phase 3 trial of DT120, the molecule formerly known as LSD, for generalized anxiety disorder.
Four months later, in April 2025, they started a separate Phase 3 program. It was an evaluation of the same compound, this time for major depressive disorder. The depression study read out top-line last week. The anxiety study? The one that started first? It is still running.
This almost never happens—trials take a predictable amount of time, like olympic athletes running around a track. Little differences are common, but lapping the other runners isn’t. The fact that GAD’s program was beaten to the finish line in another indication is news, in and of itself. The data from that trial, EMERGE, are similarly remarkable.
A psychedelic medicine program just ran its second pivotal indication faster than its first, in a field where pivotal trials traditionally run two to four years.
Your author loves a rapid acting treatment. Heck, we have a whole event series dedicated to them, with the next RAMHT event happening at Psych Congress, on September 14th, 2026. Get your tickets now!
First, we had SAINT TMS promising rapid relief from depression in just 5 days of treatment. Although that 5-day number is always true for the treatment itself, it’s only true for the response to treatment for 60% of patients. The rest of patients have a response that “can’t be rushed.” The final remission number, which is somewhere between 50-79% depending on the sample we look at, remit between 1 and 4 weeks later.
Every day with severe depression can’t end soon enough, as evidenced by the rate of suicide in sufferers being on the order of 200/100,000 lifetime risk from MDD (or more, with common comorbidities considered). This horrific outcome is hard to prevent.
The momentum continued with data from the “AINT” trial, covered by both this newsletter, and here in this article too.
Last week, we had the topline of data from the team at Definium Therapeutics, with friend of the newsletter Dan Karlin, M.D., in the CMO chair, reading out data on their trial for lead asset DT120, the compound formerly known as LSD, née, Lysergide Tartrate ODT. For more on LSD, I conveniently senior-authored a review last year for you, dear readers, in the American Journal of Therapeutics:
Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 μg dose of LSD.
Much to the surprise of us all, their readout on their concurrent MDD clinical trial program happened before their GAD readout, which is expected later this year.
The data is remarkable, let’s just get that out of the way. This is what the above text looks like when laid out in a graph:
This is among the most perfect separations between placebo and active you could hope for. The critics will quickly note that functional unblinding is highly likely. Well, of course it is. This is a psychedelic medicine, and their other clinical trial programs have active controls to solve for that problem. Not every study can demonstrate everything.
Why the timeline matters so much
The potency of the effect got the headlines—well it should, it’s the biggest deal in depression treatment ever. There are quibles to be had with that number: ”functional unblinding” is a just concern.
The schedule, however, should get the real attention. Here is what the clincal trials registry actually shows:
DT120 GAD pivotal (Voyage, NCT06741228): started December 11, 2024, primary completion projected July 2026. ~19 months.
DT120 MDD pivotal (Emerge, NCT06941844): started April 14, 2025, primary completion May 20, 2026. ~13 months.
The MDD trial started 4 months later than the GAD trial. It finished 2 months earlier. It ran roughly 6 months faster.
Perhaps the most important thing about this remarkable outcome is that it came out before the anxiety data. This is a team working at breakneck speed, such that a clinical trial program started later read out top-line earlier. For investors, that means it’s possible to speed-run a clinical trial program, which means money is moving through the system faster. Returns on investment are quicker, and the time value of money goes up. For patients waiting for relief, there’s also the hope that they can get relief faster, and this is a rare place where investment dollars and patient outcomes are highly aligned on the same outcome.
For those of us not deep in the weeds on clinical trials, none of this is usually fast. Anxiety trials take a long time to enroll, because although many people have anxiety, most people who have anxiety also have other problems, and they don’t belong in an anxiety monotherapy study. The fact that they got a depression study done even before the anxiety study finished is just not what we see in life sciences traditionally.
How fast is fast?
Among recent FDA-approved or late-stage small-molecule MDD programs, here is what pivotal trial timing looks like:
