The esketamine label: sedation in up to 61 percent, dissociation in up to 84 percent, more with sedatives or alcohol
Spravato's label: "Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation." In trials, 48 to 61 percent were sedated and 61 to 84 percent had dissociation.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The trial percentages are for esketamine nasal spray at approved doses under observation; they do not transfer directly to street ketamine of unknown dose and purity, in either direction.
Esketamine is the prescription cousin of street ketamine, and its label is the closest thing to a regulator's account of what ketamine does with other drugs.
Significant findings
SPRAVATO prescribing information (Janssen, August 2026), Drug Interactions 7.1: "Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation. Closely monitor for sedation with concomitant use of SPRAVATO with CNS depressants."
What the drug does alone, from the Warnings: "In clinical trials, 48% to 61% of SPRAVATO-treated patients developed sedation"; "61% to 84% of SPRAVATO-treated patients developed dissociative or perceptual changes"; "In post marketing experience, respiratory depression was observed with the use of SPRAVATO. In addition, there were rare reports of respiratory arrest". On blood pressure: "Approximately 3% to 19% of SPRAVATO-treated patients and 1% to 4% of placebo-treated patients experienced an increase of greater than or equal to 40 mmHg in systolic BP and/or 25 mmHg in diastolic BP in the first 1.5 hours after administration". Because of these, patients "must be monitored by a healthcare provider for at least 2 hours at each treatment session".
The label also records what long-term misuse does: "Cases of ulcerative or interstitial cystitis have been reported in individuals with long-term off-label use or misuse/abuse of ketamine."
Worth asking
A clinic gives esketamine under two hours of observation with a blood pressure cuff on. Street ketamine is the same molecule family taken with none of that, often with alcohol or a benzodiazepine, which is the combination the label says deepens sedation and, in the boxed warning, can depress breathing. The bladder line is the one recreational users rarely hear. If you use ketamine and take a benzodiazepine, an opioid, or drink, the label's own monitoring rules are the measure of the risk you are taking without them.
Source
SPRAVATO (esketamine) nasal spray: FDA-approved prescribing information, Boxed Warning, Warnings and Precautions 5.1 to 5.3, 5.7, 5.10, Drug Interactions 7.1 — Janssen Pharmaceuticals, Inc.; US Food and Drug Administration (2026)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- Industry funded
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: The trial percentages are for esketamine nasal spray at approved doses under observation; they do not transfer directly to street ketamine of unknown dose and purity, in either direction. 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?
SPRAVATO (esketamine) nasal spray: FDA-approved prescribing information, Boxed Warning, Warnings and Precautions 5.1 to 5.3, 5.7, 5.10, Drug Interactions 7.1 — Janssen Pharmaceuticals, Inc.; US Food and Drug Administration (2026). Published in: Regulator or national health body. 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: Regulatory safety determination. Funding: Industry funded. Independence from the proponent is not recorded. 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 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.