Ketamine nasal spray is administered in a supervised medical setting, not at home. The FDA-approved version, called Spravato (esketamine), requires you to visit a certified clinic where you spray the medication yourself under a healthcare provider’s watch, then stay for at least two hours of monitoring. Here’s what the full process looks like, from preparation to what happens after each session.
Two Types of Ketamine Nasal Spray
Spravato is the only FDA-approved nasal spray for treatment-resistant depression. It contains esketamine, a more potent form of the ketamine molecule. Each device delivers a pre-measured dose, and you may use one, two, or three devices per session depending on your prescribed amount (56 mg or 84 mg).
You may also encounter compounded ketamine nasal sprays, which are custom-mixed by specialty pharmacies and sometimes prescribed through telemedicine platforms. These are not FDA-approved for depression. The FDA has issued multiple safety alerts about compounded ketamine products, most recently in October 2023, citing potential safety concerns with formulations available from compounders and telemedicine services. Compounded drugs are intended only for patients whose needs can’t be met by an approved product. The rest of this article focuses on Spravato, since it has standardized dosing, a well-studied safety profile, and a defined administration protocol.
How the Treatment Schedule Works
Treatment happens in two phases. During the first four weeks (the induction phase), you visit the clinic twice per week. Each session, you self-administer either 56 mg or 84 mg alongside a daily oral antidepressant you take at home.
If you respond well, meaning your depression symptoms drop by at least 50%, you move into the maintenance phase. For the first four weeks of maintenance, sessions drop to once a week. After that, your provider adjusts to the lowest frequency that keeps your symptoms in check, which is typically once a week or once every two weeks. This maintenance phase can continue for months, with your provider re-evaluating the schedule roughly every four weeks.
Preparing Before Each Session
You’ll be asked not to eat for at least two hours before your appointment and not to drink liquids for at least 30 minutes before. If you use a nasal corticosteroid or decongestant, use it at least an hour beforehand so it doesn’t interfere with absorption.
Right before you start, gently blow your nose to clear your nostrils. You only do this once, before the first device. Do not blow your nose again after that point, since doing so can push the medication out before it absorbs.
Step-by-Step Spray Technique
Each Spravato device contains two sprays, one for each nostril. Here’s the process:
- Hold the device correctly. Grip it upright between your thumb and first two fingers. Do not press the plunger yet.
- Position your head. Tilt your head back slightly.
- Insert the tip. Place the device tip into your first nostril. The nose rest (the wider part at the base of the tip) should touch the skin between your nostrils.
- Close and spray. Use a finger to close your other nostril. Press the plunger firmly all the way up while breathing in slowly through your nose.
- Sniff gently. After the spray, sniff once softly to help the medication settle into the nasal lining.
- Switch nostrils. Repeat the same steps for the other nostril using the same device.
If your dose requires a second or third device, wait five minutes between each one to give the medication time to absorb. If any liquid drips from your nose, dab it gently with a tissue. Do not blow your nose at any point after spraying.
What Happens During the Two-Hour Monitoring
After you finish spraying, you stay in the clinic for at least two hours. This is a federal requirement under Spravato’s Risk Evaluation and Mitigation Strategy (REMS) program, and it’s the reason you cannot take this medication at home. During those two hours, a healthcare provider checks your blood pressure and watches for sedation and dissociation, the two most common effects.
Dissociation can feel like a sense of detachment from your surroundings, altered perception of time, or a floating sensation. Sedation ranges from mild drowsiness to feeling significantly sleepy. Both effects typically peak within the first 40 minutes and resolve well before the two-hour mark for most people. Your provider will confirm that these effects have cleared before you leave. You cannot drive or operate heavy machinery for the rest of the day after a session, so you’ll need someone to take you home.
How It Works in the Brain
Traditional antidepressants work on serotonin or norepinephrine, and they often take weeks to kick in. Esketamine takes a different route. It blocks a specific type of receptor involved in brain signaling, which paradoxically triggers a surge of glutamate, the brain’s primary excitatory chemical messenger. This glutamate surge activates pathways that help the brain form new neural connections, essentially helping it rewire circuits that depression has disrupted. This mechanism is why many patients notice mood improvements within hours or days rather than the weeks required by conventional antidepressants.
Managing the Bitter Taste and Nausea
One of the most frequently reported complaints is a strong, unpleasant taste that develops as the spray drains from the nasal passages into the back of the throat. This taste alone can trigger nausea and even vomiting in some patients. A simple workaround that clinics have adopted: rinsing your mouth with water about 20 to 25 minutes after spraying, then sipping a strongly flavored fruit punch drink. In documented cases, this resolved the bad taste within five minutes and stopped the associated nausea. The key is using a drink with enough flavor to mask the bitterness, not just plain water.
If nausea is a recurring problem at your sessions, your clinic may offer anti-nausea medication beforehand. Let your provider know after your first session if the taste or nausea was significant, so they can have a plan ready for subsequent visits. Since the bitter taste is the trigger in many cases, addressing it early with a flavored drink often makes anti-nausea medication unnecessary.
What to Expect Over Time
During the twice-weekly induction phase, your provider tracks your depression scores to see if you’re responding. Response is defined as at least a 50% reduction in symptom severity. If you reach that threshold, you transition into maintenance. If symptoms stay stable during maintenance, your provider will try spacing sessions further apart to find the minimum effective frequency.
Some people notice improvement after just one or two sessions, while others need the full four-week induction period. The experience during each session also tends to change over time. Side effects like dissociation and sedation are often strongest in the first few sessions and may become milder as your body adjusts. The bitter taste, however, tends to persist and is worth planning for at every visit.