Rankings / Mood, Anxiety & Stress
Ketamine
Mood, Anxiety & Stress · NMDA antagonist
Tier B-
High-risk evidence profile
Bottom line
Read Off Label grades Ketamine as B- (6.0/10) based on strong evidence, med-high benefit magnitude, and a med-high-risk safety profile.
Its high-risk evidence profile reflects a Safety score of 3.5/10; reported benefits and harms can differ by indication, dose, route, duration, and population.
Paradigm-shifting for TRD since Berman 2000 and Zarate 2006.
Studied, labeled, or reported-use context: 0. — Rx (Schedule III US); esketamine REMS program; not individualized guidance.
What the evidence says
Paradigm-shifting for TRD since Berman 2000 and Zarate 2006. Telehealth ketamine programs exploded 2020-2024 with questionable oversight; bladder damage from chronic use well-documented. Recreational use and 'K-hole' highly dissociative. Matthew Perry death from ketamine overdose October 2023.
Mechanism
Non-competitive NMDA receptor antagonist; also mu-opioid, dopaminergic, cholinergic activity; rapid-onset antidepressant; S-enantiomer (esketamine/Spravato) FDA-approved for TRD 2019
Studied, labeled, or reported dose & route
0.5 mg/kg IV over 40 min (depression); 40-85 mg intranasal esketamine
This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.
Citations
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Common questions
- What does the evidence show about Ketamine's effects?
- Read Off Label rates the evidence for Ketamine as Strong and the benefit magnitude as med-high, producing an overall grade of B- (6.0/10). Paradigm-shifting for TRD since Berman 2000 and Zarate 2006.
- What safety findings are reported for Ketamine?
- Ketamine has a med-high risk profile in the database. Med-High (dissociation, bladder/cystitis with chronic use, dependence, cardiovascular, elevated ICP) Legal status: Rx (Schedule III US); esketamine REMS program.
- What does the low Safety score for Ketamine represent?
- The Safety score is 3.5/10. It records the substantial harms described for one or more use contexts; the Benefit score, indication, dose, route, duration, population, and legal status remain separate parts of the evidence profile.
- What doses or routes are reported for Ketamine?
- 0.5 mg/kg IV over 40 min (depression); 40-85 mg intranasal esketamine This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
- How does Ketamine work?
- Non-competitive NMDA receptor antagonist; also mu-opioid, dopaminergic, cholinergic activity; rapid-onset antidepressant; S-enantiomer (esketamine/Spravato) FDA-approved for TRD 2019
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.