Ketamine is taken through several routes depending on the medical purpose: as an intravenous (IV) infusion, a nasal spray, an intramuscular injection, or in oral and sublingual (under-the-tongue) forms. For depression treatment, the two most common methods are IV infusion in a clinic and a prescription nasal spray called Spravato. Each route delivers a different amount of the drug into your bloodstream, which affects how quickly it works and how long the effects last.
IV Infusion
Intravenous infusion is the most widely studied method for treating depression with ketamine. A small catheter is placed in your arm, and the drug is delivered slowly over about 40 minutes using an infusion pump. The standard dose is 0.5 mg per kilogram of body weight, meaning a 150-pound person would receive roughly 34 mg. Because the drug goes directly into your bloodstream, bioavailability is 100 percent, and effects begin within seconds to minutes.
IV ketamine for depression is considered “off-label,” meaning it hasn’t received specific FDA approval for that purpose, though clinicians prescribe it based on strong clinical evidence. You’ll typically sit in a reclining chair in a supervised clinic setting. A course of treatment often involves multiple sessions over several weeks, though protocols vary by provider.
Nasal Spray (Spravato)
The FDA-approved nasal spray version uses esketamine, a close chemical relative of ketamine, and is sold under the brand name Spravato. It’s approved specifically for treatment-resistant depression (when at least two other antidepressants haven’t worked) and for adults with major depression who are experiencing acute suicidal thinking. Doses range from 56 mg to 84 mg per session, delivered using two or three spray devices.
The process works like this: before using the first device, you blow your nose. You then hold the device with your thumb supporting the plunger, tilt your head back about 45 degrees, insert the tip straight into one nostril, and press the plunger while breathing in gently through your nose. You repeat this in the other nostril. After each device, you rest in a semi-reclined position for five minutes. If a second or third device is needed, you repeat the process after that rest period. You should not blow your nose afterward; if liquid drips out, just dab with a tissue.
The nasal spray absorbs about 45 to 50 percent of the drug into your bloodstream, roughly half the efficiency of an IV line. To compensate, the doses are higher in milligram terms. You cannot take Spravato home. Every session takes place in a certified clinic or doctor’s office, and a healthcare professional must directly supervise administration.
Oral and Sublingual Forms
Some clinics prescribe ketamine as a lozenge (troche) or liquid that you swallow or hold under your tongue. These forms are far less efficient at delivering the drug. Sublingual administration has an average bioavailability of about 32 percent, while swallowing ketamine drops that number to roughly 23 percent. That means more than two-thirds of an oral dose is broken down by your liver before it ever reaches your brain.
The trade-off is convenience. Oral and sublingual ketamine can sometimes be prescribed for at-home use, depending on the provider and your treatment history. Because absorption is lower and more variable, the experience tends to be milder and less predictable than IV or nasal spray sessions.
What Happens During a Session
Regardless of the method, most clinics ask you to fast for a few hours beforehand. An empty stomach reduces the risk of nausea and vomiting, which are common side effects. It also allows the drug to absorb more efficiently, particularly for oral and sublingual forms. Some patients also report feeling more mentally clear and focused during the session when they haven’t eaten recently.
Once the ketamine takes effect, you may feel a sense of deep calm, detachment from your surroundings, or altered perception of sights and sounds. Some people describe floating or feeling disconnected from their body. Other common effects include rapid eye movement, dilated pupils, muscle stiffness, and temporary difficulty thinking clearly. These sensations are expected and typically fade within an hour or two after the session ends.
Blood pressure and heart rate commonly rise during treatment. In one study of 84 patients across 205 infusions, 20 to 30 percent experienced blood pressure above 180/100 mmHg or a heart rate above 110 beats per minute, and some needed medication to bring it back down. Your vitals will be monitored throughout.
The Post-Session Observation Period
After any in-clinic ketamine session, you’ll be observed for at least two hours. Staff monitor for sedation, dissociation, respiratory changes, and blood pressure spikes. You won’t be cleared to leave until a clinician determines you’re stable. You cannot drive or operate machinery for the rest of the day, so you’ll need someone to take you home.
Who Should Not Take Ketamine
Ketamine raises blood pressure, which makes it risky for certain cardiovascular conditions. The nasal spray form is specifically contraindicated for people with cerebral aneurysms, a history of bleeding in the brain, or abnormal blood vessel formations in the brain. Providers will typically check your blood pressure before every session and may delay or cancel treatment if it’s already elevated. If you have uncontrolled hypertension or a history of stroke, your provider will weigh those risks carefully before starting treatment.