Question 1

- question: "What is the typical dose of ketamine for depression?

Accepted Answer

The most widely studied and commonly used dose for intravenous ketamine in the treatment of depression is 0.5 mg/kg administered over 40 minutes. This [sub-anesthetic dose](/dosing/sub-anesthetic-dose-ranges/) was established in the landmark Berman et al. (2000) study and has been replicated in numerous subsequent clinical trials. For context, a 70 kg (154 pound) individual would receive approximately 35 mg. Some providers may start at a lower dose of 0.3 to 0.4 mg/kg for the first session and titrate upward based on tolerability and response. Doses above 0.5 mg/kg, up to 0.75 or 1.0 mg/kg, are sometimes used when the standard dose produces insufficient response, though higher doses increase the likelihood of side effects.

Question 2

What are the different ways ketamine can be administered?

Accepted Answer

Ketamine can be administered through several routes, each with distinct characteristics. Intravenous (IV) infusion offers the highest bioavailability at nearly 100 percent and allows precise dose control. Intramuscular (IM) injection provides approximately 93 percent bioavailability and does not require IV access. Intranasal administration, used for FDA-approved esketamine (Spravato), has a bioavailability of about 25 to 50 percent. Sublingual troches or lozenges, which dissolve under the tongue, have a bioavailability of approximately 25 to 30 percent. Oral capsules or liquid have the lowest bioavailability at roughly 17 to 20 percent due to extensive first-pass liver metabolism. Your provider will recommend the most appropriate route based on your clinical needs, treatment setting, and practical considerations.

Question 3

How is ketamine dose calculated based on body weight?

Accepted Answer

Ketamine dosing for psychiatric indications is weight-based, calculated in milligrams per kilogram (mg/kg) of body weight. For intravenous administration, the standard dose is 0.5 mg/kg. To calculate your dose, divide your weight in pounds by 2.2 to get kilograms, then multiply by the target mg/kg dose. For example, a 180-pound patient weighs approximately 82 kg and would receive about 41 mg at the 0.5 mg/kg dose. For sublingual and oral routes with lower bioavailability, higher absolute doses are prescribed to achieve comparable plasma levels. For more on this, see [weight-based dosing guidelines](/dosing/weight-based-dosing-guidelines/). Some providers use ideal body weight rather than actual body weight for obese patients, though practices vary. Dosing should always be determined by a qualified clinician.

Question 4

When and why would a dose be adjusted?

Accepted Answer

Dose adjustments are made based on two primary factors: tolerability and efficacy. If a patient experiences significant side effects such as severe dissociation, persistent nausea, or marked blood pressure elevation, the dose may be reduced by 0.05 to 0.1 mg/kg increments. Conversely, if a patient shows minimal response and tolerates the initial dose well, a gradual increase to 0.6 or 0.75 mg/kg may be attempted. Some clinicians also adjust the infusion rate rather than the total dose, extending the infusion from 40 to 60 minutes to reduce peak plasma concentrations and side effects. The goal is to find the minimum effective dose that produces therapeutic benefit with acceptable tolerability.

Question 5

What is the difference between at-home and in-clinic ketamine treatment?

Accepted Answer

In-clinic treatment typically involves intravenous infusions or intranasal esketamine administered under direct medical supervision with continuous vital sign monitoring. This setting allows for immediate management of adverse events and precise dose control. At-home ketamine treatment usually involves [sublingual troches or oral formulations](/protocols/sublingual-and-oral-protocols/) prescribed by a telehealth provider, with the patient taking the medication in a comfortable home environment. At-home treatment requires a sober monitor present during sessions and typically uses lower-risk oral or sublingual routes. While at-home treatment is more convenient and often less expensive, it lacks the real-time medical monitoring available in clinics. Both approaches have demonstrated efficacy, and the appropriate choice depends on individual clinical needs and risk factors.

Question 6

What is the difference between ketamine and esketamine?

Accepted Answer

Ketamine is a racemic mixture containing two mirror-image molecules: S-ketamine (esketamine) and R-ketamine (arketamine). Esketamine, marketed as Spravato, is the isolated S-enantiomer and was approved by the FDA in 2019 for treatment-resistant depression. Esketamine has approximately four times the binding affinity for the NMDA receptor compared to R-ketamine and is roughly twice as potent by weight as racemic ketamine. However, racemic ketamine contains both enantiomers, and preclinical research suggests R-ketamine may have its own unique antidepressant properties with fewer dissociative side effects. The choice between the two often depends on insurance coverage, provider preference, and the specific treatment setting.

Question 7

Can the dose be too low to be effective?

Accepted Answer

Yes. Research has shown that there is a minimum threshold dose below which ketamine does not produce reliable antidepressant effects. Studies examining very low doses of 0.1 to 0.2 mg/kg intravenously have generally found them to be no more effective than placebo for depression, although they may still have some utility in pain management. The active control dose of 0.045 mg/kg midazolam used in many ketamine clinical trials produces sedation but no antidepressant effect, confirming that a sufficient ketamine dose is necessary for therapeutic benefit. If you are receiving sublingual or oral ketamine, the lower bioavailability of these routes means that the prescribed milligram amount will be higher than the equivalent IV dose to ensure adequate drug exposure.

Question 8

How is dosing different for intranasal esketamine (Spravato)?

Accepted Answer

Intranasal esketamine (Spravato) uses a fixed-dose approach rather than the weight-based dosing used for IV ketamine. The FDA-approved protocol specifies two dose levels: 56 mg and 84 mg. Treatment begins at 56 mg for the first two sessions. Based on tolerability and efficacy, the dose may be increased to 84 mg or maintained at 56 mg. During the induction phase, treatment is administered twice weekly for four weeks. The consolidation phase involves once-weekly sessions for four weeks. The maintenance phase reduces frequency to once weekly or once every two weeks. Each session requires a two-hour monitored observation period at a certified healthcare facility, as the REMS (Risk Evaluation and Mitigation Strategy) program requires on-site administration.

Dosing and Administration

Frequently Asked Questions

Related Reading

Low-Dose Ketamine and Cannabis: What Patients Should Know

Drug Interactions and Contraindications

Ketamine for Depression