The standard ketamine dose for treating depression is 0.5 mg/kg administered as an intravenous infusion over 40 minutes. This means a 70 kg (154 lb) patient would receive approximately 35 mg of ketamine. This specific dose and infusion rate were established through the landmark 2006 National Institute of Mental Health study by Zarate and colleagues, and it remains the most widely studied and clinically used protocol for depression treatment.
Why 0.5 mg/kg?
The 0.5 mg/kg dose occupies a pharmacological sweet spot in the sub-anesthetic range. At this level, ketamine achieves an estimated 50 to 70 percent occupancy of NMDA receptors in the brain -- enough to trigger the downstream molecular cascade involving glutamate release, AMPA receptor activation, and BDNF-mediated synaptogenesis that underlies the antidepressant effect, but well below the threshold for general anesthesia (which typically requires 1 to 2 mg/kg IV).
Dose-finding studies have compared the 0.5 mg/kg dose against lower doses such as 0.1 and 0.2 mg/kg. Fava and colleagues (2020), publishing in Molecular Psychiatry, found that 0.5 mg/kg produced significantly greater antidepressant effects than lower doses, which did not consistently separate from active placebo. Higher doses, approaching 1.0 mg/kg, did not show clearly superior antidepressant efficacy but did produce more intense dissociative side effects.
Other Routes and Doses
While the 0.5 mg/kg IV infusion is the gold standard, ketamine is also administered by other routes with adjusted dosing. Sublingual (under the tongue) ketamine typically uses doses of 0.5 to 1.0 mg/kg to compensate for lower bioavailability (approximately 25 to 30 percent vs. 100 percent IV). Intramuscular injection uses similar weight-based dosing to IV but with a slower onset and longer duration. Intranasal esketamine (Spravato), the FDA-approved S-enantiomer formulation, uses fixed doses of 56 or 84 mg regardless of body weight.
Clinicians may adjust doses by increments of 0.1 mg/kg between sessions based on a patient's response and side effect experience. Use our dose calculator for weight-based reference calculations, and see the Ketamine Dosing and Administration Guide for complete dosing protocols.
References
- PubMed: A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression — Zarate et al. (2006), establishing the 0.5 mg/kg IV dose as the standard protocol
- PubMed: Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine — Fava et al. dose-finding study comparing multiple ketamine doses
- Mayo Clinic: Treatment-Resistant Depression — Mayo Clinic overview of treatment options for refractory depression
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