Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With…
If this works for me, what is the plan and timeline for ever stopping it?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Randomized-withdrawal designs can overstate maintenance benefit (abrupt discontinuation effects count as "relapse"); sponsor-funded and sponsor-authored.
esketamine (Spravato) only — TRD 2019, monotherapy Jan 2025, REMS in force. Racemic ketamine is approved as an anesthetic; its psychiatric use is off-label.
Among 297 patients stabilized on esketamine (SUSTAIN-1), continuing esketamine plus antidepressant halved relapse risk vs switching to placebo spray (relapse 27% vs 45% in stable remitters; NNT 6) — evidence for maintenance benefit, and also that stopping esketamine carries a real relapse risk.
Worth asking
If this works for me, what is the plan and timeline for ever stopping it?
What it is FDA approved for
Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.
- Treatment-resistant depression (esketamine nasal spray, with oral antidepressant; monotherapy since Jan 2025) · approved 2019 · trials ran 4-week pivotal trial (TRANSFORM-2, day-28 endpoint)
- Depressive symptoms in MDD with acute suicidal ideation or behavior (esketamine, with oral antidepressant) · approved 2020
- Anesthesia (racemic ketamine only; all psychiatric use of racemic ketamine is off-label)
Source
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial — Daly EJ, et al. (2019)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jamapsychiatry.2019.1189
DOI: 10.1001/jamapsychiatry.2019.1189
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Industry funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 297
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Where we put this study in context
Questions
How strong is the evidence behind this?
Resolv rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 59 out of 100 on our published rubric. One caveat travels with that badge: Randomized-withdrawal designs can overstate maintenance benefit (abrupt discontinuation effects count as "relapse"); sponsor-funded and sponsor-authored. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial — Daly EJ, et al. (2019). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jamapsychiatry.2019.1189. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Industry funded. The researchers were not independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is esketamine, spravato FDA approved?
Yes — FDA approved for Treatment-resistant depression (esketamine nasal spray, with oral antidepressant; monotherapy since Jan 2025), Depressive symptoms in MDD with acute suicidal ideation or behavior (esketamine, with oral antidepressant), Anesthesia (racemic ketamine only; all psychiatric use of racemic ketamine is off-label). Approval is for a specific indication, not for everything the drug is prescribed for.
Where is this treatment in the FDA pipeline?
FDA approved. esketamine (Spravato) only — TRD 2019, monotherapy Jan 2025, REMS in force. Racemic ketamine is approved as an anesthetic; its psychiatric use is off-label.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.