Sold as Spravato.
First FDA approval 03/05/2019: 7 years on the US market.
This grade answers one narrow question: how strong is the public evidence and safety record behind this drug, and how clean is its money trail and court record? It is not a verdict on whether the drug is right for you.
B
Score breakdown (77/100)
Safety ×35%
A
Evidence ×25%
C
Regulatory ×15%
B
Money & lawsuits ×15%
C
Options ×10%
F
Safety: 90
Prescrire lists one form only (esketamine nasal spray) as a drug to avoid; shown for context, no score effect
Subject to a REMS safety program: FDA requires special controls to use it (-10)
Death share in reports is near or below the FAERS average (0.4x)
Evidence: 71
349 randomized trials and 134 systematic reviews/meta-analyses indexed in PubMed
1 independent Cochrane review(s) exist
Only 16% of completed registered trials posted results (-15)
Regulatory history: 86
No recalls on record since 2016
REMS program in force (-10)
4 label changes approved since 2021 (-4)
Money & lawsuits: 70
Pharma paid doctors $6,147,423 tied to this drug last year (-30)
Not named in any pending federal MDL
Options: 40
No generic version approved: brand-only pricing (-30)
No same-class alternatives found: little leverage to switch (-30)
Independent reviews and post-approval warnings
Prescrire: drug to avoid (esketamine nasal spray only)
This verdict covers esketamine nasal spray, not every form of the drug, so it does not affect the grade.
Esketamine nasal spray is authorised for use in “treatment-resistant” depression and depression with a high risk of suicide, but its efficacy is highly uncertain. Its neuropsychiatric adverse effects are common and include dissociative symptoms. An increased risk of suicide was reported in the weeks following treatment. Addiction and misuse are likely (Prescrire Int n° 222, 238; Rev Prescrire n° 494). In both of these difficult clinical situations, it is more prudent to consider other less dangerous options, even if their efficacy is uncertain, for example: psychotherapy, sometimes with hospit...
Prescrire is a French independent review funded only by subscribers, with no industry money. Its annual "drugs to avoid" list (2026 edition, section: Haematology) names drugs it judges more harmful than useful in every authorised indication. Its view is one expert opinion, reached without a conflict of interest.
What the FDA label says
Approved uses
Not available.
Contraindications
None listed.
Warnings and precautions
Not available.
Adverse reactions (label)
Not available.
Source: FDA SPL label, effective .
Side-effect reports sent to the FDA
These are counts of reports people filed, not rates of harm. Anyone can file one, and nobody checks whether the drug was the cause. Millions of doses are taken for every report sent, so the useful part is how this drug compares with the average across all drugs.
18,675reports that mention this drug
18,646of those blame this drug, not another one the person was taking
71%of reports describe a serious outcome, such as a hospital stay (average for all drugs: 57%)
4.1%of reports include a death, from any cause (average for all drugs: 9.1%)
Source: the FDA's Adverse Event Reporting System (FAERS). Reports are voluntary and unverified. Drugs that are prescribed a lot, in the news, or in lawsuits attract more reports, so the percentages are compared with the whole database to correct for that partly, not fully.
Counts measure how much evidence exists and how transparent it is, not how big the benefit is. For that, ask your prescriber: if 100 people like me took this, how many would get better because of it, and how many would be harmed? (Doctors call these the "number needed to treat" and "number needed to harm.") It differs by condition and is the number drug ads leave out. Sources: PubMed, ClinicalTrials.gov.
Money and lawsuits
In 2024, drug companies reported $6,147,423 in payments to US physicians and hospitals tied to this drug across 47,112 transactions (Spravato $6,147,423).
No pending federal MDL names this drug or its brands.
Not named in any federal pharmaceutical settlement of $100M or more on record.
Sources: CMS Open Payments (Sunshine Act); Judicial Panel on Multidistrict Litigation pending docket list; DOJ settlements as tabulated on Wikipedia with links to the primary record. State-court and individual suits are not included.
Who takes it and what it costs
5,542Medicare Part D patients (2024)
84,544prescriptions filled
$1,516average cost per fill
$128Mtotal Medicare spend
Same-class alternatives
No same-class alternatives found in RxClass.
Questions to ask your prescriber
An independent reviewer (Prescrire) lists this as a drug to avoid because the harms outweigh the benefits versus alternatives. What is your view on that?
This drug has a REMS safety program. What monitoring does that require from us?
The most-reported problems in FDA's adverse event data are dissociation, sedation, suicidal ideation. How would we recognize and handle those?
There is no generic. Is there an older generic in the same class that works as well for my situation?
The manufacturer pays physicians heavily to promote this drug. Have you received anything from them?
What result are we expecting, by when, and what is the plan if it does not happen?
If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)