ketamine

General Information

Ketamine (brand Ketalar; generics) is a dissociative anesthetic used for anesthesia and procedural sedation (label). It is increasingly used off-label in monitored settings for treatment-resistant depression (TRD) and acute suicidal ideation, based on rapid-onset antidepressant effects in some patients (consensus/clinical).

Unlike Esketamine (Spravato), ketamine is not FDA-approved for depression. Most psychiatric protocols treat ketamine as a monitored procedure with structured symptom tracking rather than a take-home prescription (consensus).

Acute effects can include dissociation and short-lived sedation, which is why protocols commonly include on-site observation and functional safety planning (transportation and activity restrictions) after the session (consensus/clinical).

Ketamine can increase blood pressure and heart rate during administration, so screening and session vital sign monitoring are typical (label/consensus).

The compare view, ketamine evidence feed, and ketamine print page help align expectations about rapid symptom change with the safety and access logistics of treatment.

Ketamine use for depression is off-label and typically delivered in clinics that can monitor vitals and mental status during and after the session. Access, cost, and local protocol variability are common practical considerations.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Non-competitive NMDA receptor antagonism alters glutamatergic signaling, producing dissociation at higher exposures and, in some patients, rapid-acting antidepressant effects at subanesthetic exposures (mechanism/consensus).

Downstream synaptic plasticity and circuit-level changes are proposed mechanisms for mood improvement; ketamine’s metabolite norketamine also has NMDA activity (label/mechanism).

• NMDA receptor antagonism; dissociative anesthetic effects.

Metabolism and Pharmacokinetics

• Ketamine is metabolized via N-dealkylation to norketamine primarily by CYP2B6 and CYP3A4 (label).
• Label describes a redistribution (beta) half-life of ~2.5 hours after IV administration; clinical effects of anesthesia are shorter than the beta phase (label).
• Norketamine is the major circulating metabolite and has NMDA activity but lower affinity than ketamine (label).

Dosing and Administration

• Label dosing depends on the clinical indication (anesthesia/sedation) and route (IV or IM). Dosing for psychiatric indications is off-label (label/consensus).
• Consensus statements for mood disorders describe commonly used monitored infusion protocols (often weight-based over a short infusion) with observation during and after the session (consensus).
• When ketamine is used repeatedly, protocols often include structured symptom rating and reassessment of ongoing need, because benefit can be rapid but may not persist without maintenance planning (consensus/clinical).

Monitoring & Labs

• During dosing sessions: monitor blood pressure, heart rate, and mental status (dissociation/sedation) (label/consensus).
• When used repeatedly: track symptom response over time and ask about urinary symptoms and substance use risk (clinical).

Monitoring practices vary by protocol because psychiatric use is off-label; consensus statements emphasize structured follow-up.

Adverse Effects

Interactions

• CNS depressants (alcohol, benzodiazepines, opioids) can compound sedation and impairment (label/clinical).
• Strong CYP2B6 or CYP3A4 modulators may alter exposure; medication reconciliation is commonly done before sessions (label/clinical).
• Sympathomimetic agents and stimulants can compound blood pressure and heart rate increases during sessions (clinical).

Other Useful Information

• Ketamine’s depression use is off-label; FDA-approved intranasal esketamine is a separate product with a labeled REMS-based monitoring model (consensus/label).
• Safety planning often includes transportation logistics and avoidance of high-risk activities (driving/operating machinery) until the effects have fully worn off (consensus).

References

1. KETALAR (ketamine hydrochloride) injection prescribing information — DailyMed (2025)
2. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders — JAMA Psychiatry (2017)
3. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
4. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)