Head to head with the standard alternative.
Most depression medications are only tested against a placebo. ESCAPE-TRD tested Spravato against a real, commonly used treatment, in people whose depression hadn’t responded to at least two antidepressants. Spravato came out ahead, and stayed ahead.
Who was in it, and what they compared.
- 676 adults with treatment-resistant depression.
- Two groups: Spravato nasal spray, or quetiapine extended-release, a medication often added when antidepressants aren’t enough.
- Everyone also kept taking an oral antidepressant.
- The main measure: remission at week 8, meaning depression scores low enough to count as minimal. People were followed to week 32.
Spravato: the head-to-head data.
Spravato was tested head-to-head against another real treatment, in 676 people who had already failed at least two antidepressants. Most depression drugs are only ever tested against a placebo.
More than half in remission at week 32, against about a third on the comparator. Fewer people stopped because of side effects, too — 4.5% against 10.1%. Straight lines between the timepoints the trial published. Reif A, et al. N Engl J Med 2023;389:1298–1309.
Ahead at week 8, further ahead at week 32.
- Week 8: 27.1% in remission on Spravato, 17.6% on quetiapine.
- Week 32: 55.7% against 36.3%.
- Stopped because of side effects: 4.5% on Spravato, 10.1% on quetiapine.
Better results, and easier to stay on.
More than half the people on Spravato were in remission by eight months, and fewer than half as many stopped because of side effects. For someone whose earlier medications didn’t work, that’s the most relevant comparison there is.
Two antidepressants didn’t work? You’re who this trial studied.
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Request an evaluationWhat the trial doesn’t tell us.
- It was open-label: patients and doctors knew which treatment each person was on, though the people scoring depression didn’t. That’s hard to avoid when one treatment is a nasal spray given in a clinic.
- It compared Spravato with one alternative, not with IV ketamine, TMS or ECT.
- It ran 32 weeks. Longer-term results come from other studies.
Who will be in the 55.7%.
No test predicts who will respond. Past antidepressants not working doesn’t predict it either, because Spravato acts on a different system.
What people ask about the trial.
What is the ESCAPE-TRD trial?
A large trial, published in the New England Journal of Medicine in 2023, that compared Spravato with quetiapine in 676 adults with treatment-resistant depression, all also taking an oral antidepressant.
What did ESCAPE-TRD find?
More people reached remission on Spravato: 27.1% against 17.6% at week 8, and 55.7% against 36.3% at week 32. Fewer stopped because of side effects (4.5% against 10.1%).
Why compare Spravato with quetiapine?
Quetiapine is one of the medications commonly added when antidepressants aren’t working, so it’s a realistic alternative for the same patients.
Was ESCAPE-TRD paid for by the manufacturer?
Yes. It was sponsored by Janssen, which makes Spravato, as most large drug trials are sponsored by the drug’s maker. The results were published in a peer-reviewed journal.