Yes, ketamine is prescribed for depression, but with important distinctions depending on the form. The FDA approved a nasal spray version called Spravato (esketamine) in 2019 for treatment-resistant depression in adults. Intravenous ketamine is also widely used in clinics across the country, though that form remains off-label for psychiatric use. Both require in-office administration and monitoring.
Who Qualifies for Ketamine Treatment
Ketamine-based treatments are not a first option. They’re reserved for people whose depression hasn’t responded to standard antidepressants. The clinical threshold is straightforward: if at least two different antidepressants, each taken at an adequate dose for six to eight weeks, haven’t improved your symptoms, your depression is considered treatment-resistant. That’s the primary group ketamine treatments are designed for.
The FDA-approved nasal spray also has a second indication: adults with major depressive disorder who are experiencing acute suicidal thoughts or behavior. In both cases, the nasal spray is typically used alongside an oral antidepressant rather than completely replacing one.
How Ketamine Works Differently Than Antidepressants
Traditional antidepressants target serotonin, norepinephrine, or dopamine and can take weeks to produce noticeable effects. Ketamine works through an entirely different system. It temporarily blocks certain receptors in the brain, which triggers a cascade of glutamate release. Glutamate is the brain’s primary excitatory chemical messenger. This burst of activity strengthens connections between neurons and essentially resets synaptic function in areas involved in mood regulation.
What makes this significant is that the antidepressant effects persist after the drug itself has left the body. The temporary blockade kicks off lasting changes in how brain cells communicate, which is why a single infusion can produce relief that outlasts the drug’s presence by days or even weeks.
Response Rates and How Quickly It Works
Ketamine’s speed is its most striking feature. A typical induction phase involves four to eight infusions spread over one to four weeks. In a real-world analysis of 537 patients who completed induction, about 54% showed a meaningful response (defined as at least a 50% reduction in depression scores) within 14 to 31 days. Roughly 29% achieved full remission, meaning their symptoms dropped to minimal levels.
Those numbers are notable for a population where, by definition, at least two other medications have already failed. A 50% response rate in treatment-resistant patients represents a significant option for people who may have been struggling for years without adequate relief.
The Two Main Forms: Nasal Spray vs. IV Infusion
The nasal spray (esketamine) and IV ketamine infusions are the two primary routes, and they differ in regulation, cost, and accessibility.
Esketamine Nasal Spray
This is the only FDA-approved ketamine product for depression. It uses esketamine, one of the two mirror-image molecules that make up ketamine. Because of its risks, the FDA requires it to be administered under a strict safety program. You take the spray in a certified healthcare setting, and staff monitor you for at least two hours afterward. You cannot take the medication home. The clinic must enroll in a federal monitoring program, train its staff, and submit a patient monitoring form after every single session.
IV Ketamine Infusions
Intravenous ketamine uses the original compound and is administered off-label at specialized clinics. The standard dose is 0.5 mg per kilogram of body weight, infused over about 40 minutes. Research shows clinical benefit at doses as low as 0.2 mg/kg, with stronger responses at 0.5 mg/kg. Higher doses haven’t shown clear additional benefit. These infusions are not FDA-approved for depression, which means insurance coverage is inconsistent and out-of-pocket costs can be substantial.
Side Effects During and After Treatment
The most common side effects are dissociation (a temporary feeling of disconnection from your body or surroundings), nausea, headache, and anxiety. These effects are typically short-lived, resolving within the monitoring window after each session.
Blood pressure changes are the most medically significant concern. Between 10% and 50% of patients experience a temporary spike during infusion. In one study of 84 patients, 20 to 30% had blood pressure readings exceeding 180/100 during treatment, and about 12% needed medication to bring it back down. These spikes happen more often during the first three sessions and are more common in older patients and those with a history of high blood pressure. The nasal spray is specifically contraindicated in people with certain vascular conditions, including brain aneurysms or a history of bleeding in the brain.
This is exactly why both forms require in-clinic monitoring. The dissociation and blood pressure effects are manageable when a provider is present but could be dangerous without supervision.
Compounded Ketamine and At-Home Use
You may have seen telehealth companies offering ketamine lozenges, tablets, or nasal sprays that you can take at home. These are compounded products, meaning they’re mixed by specialty pharmacies rather than manufactured under FDA oversight. The FDA has issued a direct warning about these products, stating it has not determined that ketamine is safe or effective for any psychiatric use in these forms.
The risks are real. The FDA cited a case where a patient taking compounded oral ketamine at home for PTSD experienced dangerously slowed breathing, with blood levels reaching twice the concentration typically used for surgical anesthesia. Because compounded products vary in dosage and formulation, it’s difficult to predict how much drug actually enters your bloodstream. Without a healthcare provider present, there’s no one to intervene if sedation, dissociation, or a blood pressure spike becomes serious.
The core issue is straightforward: ketamine causes sedation, altered consciousness, and cardiovascular changes. Those effects require monitoring. At-home use removes that safety net.
What Treatment Actually Looks Like
If you’re referred for ketamine treatment, the process follows a predictable pattern. You’ll go to a clinic, receive the medication (either through an IV or nasal spray), and stay for observation. During the infusion or shortly after, you’ll likely feel some degree of dissociation, which patients often describe as floating, feeling detached, or experiencing altered perception. This passes relatively quickly.
The induction phase typically involves multiple sessions over a few weeks. After that, if you respond well, you’ll transition to a maintenance schedule with less frequent sessions. The spacing depends on how long your symptom relief lasts between treatments. Some people return monthly, others less frequently. Ketamine is generally used as an ongoing treatment rather than a one-time cure, since symptoms tend to return over time without continued sessions.
Cost remains a significant barrier. IV infusions typically run several hundred dollars per session and are often not covered by insurance. The nasal spray has broader insurance coverage due to its FDA approval, but prior authorization requirements and copays can still be substantial.