Ketamine is administered through several routes, with the method depending on whether it’s being used for anesthesia, depression, or pain management. The most common options are intravenous (IV) infusion, intramuscular (IM) injection, nasal spray, and oral or sublingual forms. Each route delivers different amounts of the drug into your bloodstream and produces effects on different timelines, so the choice shapes your entire treatment experience.
Intravenous Infusion
IV infusion is the most widely used method for treating depression and chronic pain outside of a surgical setting. A small catheter is placed in your arm, and the medication drips into your bloodstream over a controlled period. The standard dose for depression is 0.5 mg/kg of body weight, though some people respond to doses as low as 0.1 mg/kg while others need up to 0.75 mg/kg. IV delivery has the highest bioavailability of any route, around 97%, meaning nearly all of the drug reaches your system.
A typical infusion lasts about 40 minutes, though sessions ranging from 2 to 100 minutes have been studied and shown to be both safe and effective. You’ll sit in a reclining chair during the infusion while a provider monitors your blood pressure, heart rate, and oxygen levels. Most people feel the effects within minutes. The dissociative and mood-altering sensations generally fade within an hour or two after the drip stops.
For depression treatment, the initial phase usually involves six infusions given three times per week over two weeks. If you respond well, maintenance infusions drop to once per week. Research published in the American Journal of Psychiatry found that depressive symptoms remained stable when patients transitioned from three infusions per week down to one, suggesting the less frequent schedule is enough to sustain the benefit.
Intramuscular Injection
IM injection delivers ketamine through a shot, typically into the upper arm or thigh. This route has a bioavailability of 93%, nearly as high as IV, and doesn’t require an IV line. Effects begin within 3 to 5 minutes and peak within 5 to 30 minutes. In surgical settings, a standard dose produces 12 to 25 minutes of anesthesia.
For mental health treatment, IM injections use much lower doses than anesthesia. The experience is quicker to set up than an IV infusion since there’s no catheter or drip involved. Some clinics prefer this method for its simplicity, though it gives providers slightly less control over how fast the drug enters your system compared to a carefully timed IV drip.
Nasal Spray (Esketamine)
The FDA approved a nasal spray form called esketamine (brand name Spravato) specifically for treatment-resistant depression. This uses a slightly different molecule, the “S” mirror image of ketamine, rather than the full ketamine mixture used in IV and IM protocols.
You self-administer the spray under direct supervision at a certified healthcare facility. You cannot take it home. After spraying, you’re required to stay for at least two hours of monitoring before your provider clears you to leave. This restriction exists because of the risk of sedation and dissociation, and it’s enforced through a federal program that certifies which clinics can dispense the drug. You’ll also need someone to drive you home afterward.
The nasal spray route appeals to people who want to avoid needles entirely, though the mandatory in-office monitoring means each visit still takes a significant chunk of your day.
Oral and Sublingual Forms
Oral ketamine, often prescribed as lozenges (called troches) or liquid, is the form most commonly used at home. However, it absorbs far less efficiently than IV or IM routes. Oral bioavailability sits between 17% and 29% because the liver breaks down much of the drug before it reaches your bloodstream. That means you need a higher dose to get a comparable effect, and the results are less predictable from session to session.
Sublingual troches are designed to improve absorption. You place the lozenge under your tongue and let it dissolve completely, then hold the liquid in your mouth for at least 15 minutes before spitting it out. Swallowing is safe but can cause nausea and further reduces absorption. Sublingual wafer preparations have shown bioavailability around 29%, a modest improvement over simply swallowing the drug. Some researchers have argued that when you account for the active byproduct the liver produces (norketamine), the effective bioavailability of oral ketamine may reach closer to 59%, which could help explain why oral dosing sometimes performs comparably to IV in clinical studies.
Peak blood levels from oral ketamine arrive anywhere from 20 minutes to 2 hours after dosing, a much wider and slower window than IV or IM routes. The tradeoff is convenience: oral forms can be prescribed for home use, eliminating the need for clinic visits with every dose.
What’s FDA-Approved vs. Off-Label
Only two administration routes carry full FDA approval for ketamine itself: intravenous and intramuscular injection, both approved under the brand name Ketalar for anesthesia. The nasal spray esketamine (Spravato) has its own separate FDA approval for treatment-resistant depression. Every other use of ketamine, including IV infusions for depression, IM injections for mood disorders, and all oral or sublingual prescriptions, is considered off-label. Off-label doesn’t mean unsafe or unproven; it means the FDA hasn’t formally reviewed and approved the drug for that specific purpose through that specific route. Physicians legally prescribe off-label treatments regularly across all areas of medicine.
How the Routes Compare
- IV infusion: 97% bioavailability, effects in seconds to minutes, requires a clinic visit with monitoring, most studied route for depression
- IM injection: 93% bioavailability, effects in 3 to 5 minutes, requires a clinic visit, simpler setup than IV
- Nasal spray (esketamine): FDA-approved for depression, self-administered at a certified clinic, mandatory 2-hour observation
- Oral/sublingual: 17 to 29% bioavailability, effects in 20 to 120 minutes, can be used at home, least predictable absorption
The route your provider recommends will depend on what condition is being treated, how quickly effects need to begin, and whether home use or clinical supervision makes more sense for your situation. People seeking treatment for depression most often start with either IV infusions or the esketamine nasal spray, while oral troches tend to be introduced as a maintenance option once a response has been established.