Ketamine therapy uses low doses of ketamine, a powerful anesthetic, to treat depression and other mental health conditions. Originally approved by the FDA solely for anesthesia, ketamine has gained significant attention over the past decade for its rapid antidepressant effects, particularly in people who haven’t responded to conventional medications. It works differently from traditional antidepressants and can produce noticeable mood improvements within hours rather than weeks.
How Ketamine Works in the Brain
Traditional antidepressants target serotonin or similar chemical messengers and typically take four to six weeks to show results. Ketamine takes a completely different path. It blocks a specific type of receptor in the brain that responds to glutamate, the brain’s most abundant excitatory chemical signal. By temporarily blocking these receptors, ketamine triggers a cascade of changes that strengthen the connections between brain cells.
This process essentially helps the brain rebuild and reinforce synapses, the tiny gaps where neurons communicate with each other. Depression is associated with weakened or lost synaptic connections in brain regions that regulate mood and stress. Ketamine appears to reverse some of that damage rapidly, which explains why patients can feel improvement within hours of a single session. These mechanisms likely work together in complementary ways, producing both the acute mood lift and the more sustained antidepressant effects that follow.
What Ketamine Therapy Is Approved For
This distinction matters: ketamine itself is not FDA-approved for treating any psychiatric disorder. It is a Schedule III controlled substance approved only as an injectable anesthetic for surgical procedures. When clinics offer ketamine infusions for depression, anxiety, PTSD, or OCD, they are prescribing it “off-label,” meaning it’s a legal but unapproved use.
There is, however, a closely related drug that does have FDA approval for mental health treatment. Spravato, a nasal spray containing esketamine (one half of the ketamine molecule), is approved for two specific situations: treatment-resistant depression in adults, and depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior. In both cases, it must be used alongside an oral antidepressant, not on its own. Spravato can only be administered under direct supervision of a healthcare provider through a restricted program, meaning you cannot take it home.
How Effective It Is
The evidence for ketamine in treatment-resistant depression is compelling, especially for people who haven’t improved on standard medications. In a randomized controlled trial comparing a single IV ketamine infusion to an active placebo, 64.8% of ketamine patients responded to treatment compared to 28% of those receiving the placebo. Response here means a meaningful, measurable reduction in depression symptoms, not just feeling slightly better.
Repeated sessions appear to improve those numbers further. In an open-label study where patients received up to six infusions over two weeks, the response rate climbed to 70.8%. Intranasal ketamine has also shown promise, though with somewhat lower response rates. One pilot trial found a 44% response rate for intranasal ketamine versus just 6% for saline placebo. These are notable results for a population that, by definition, has already failed multiple other treatments.
The catch is durability. The rapid mood improvements from a single infusion tend to peak within 24 to 72 hours and can fade within one to two weeks. That’s why most treatment protocols involve a series of sessions, often followed by periodic maintenance infusions to sustain the benefits.
What a Session Looks Like
Ketamine therapy sessions vary depending on the delivery method, but the general experience follows a predictable pattern. For IV infusions, the most common clinical format, a low dose is administered slowly over about 40 minutes. You sit in a reclining chair, often with dimmed lights and calming music, while a provider monitors your vital signs including heart rate, blood pressure, and oxygen levels throughout the session.
During the infusion, most people experience some degree of dissociation, a feeling of detachment from your body and surroundings that patients often describe as floating or dreamlike. Some people find this pleasant, others find it unsettling, but the sensation is temporary and typically resolves within 30 to 60 minutes after the infusion ends. You’ll be monitored for at least 30 minutes after your last dose before being cleared to leave, and you’ll need someone to drive you home.
For Spravato (the nasal spray), the process is similar in structure. You self-administer the spray under a provider’s supervision, then remain in the clinic for observation, usually about two hours. A standard initial course for either approach typically involves six to eight sessions over the first month, with the frequency tapering after that based on your response.
Side Effects and Risks
Short-term side effects during and immediately after a session are common but generally resolve quickly. Dissociation is the most prominent, along with dizziness, nausea, increased blood pressure, and sometimes visual disturbances. Some people experience anxiety or confusion during the session itself. These effects almost always clear within a couple of hours.
Long-term risks are a more serious consideration. Tolerance develops quickly with ketamine, meaning the same dose produces less effect over time. This is primarily a concern with frequent or recreational use rather than supervised clinical sessions, but it underscores why treatment is typically spaced out and monitored. The most significant long-term risk documented in the medical literature involves bladder damage. Chronic ketamine use can cause a painful condition involving bladder inflammation, shrinkage, frequent urination, incontinence, and in severe cases, irreversible urinary tract damage. Studies of recreational users have found that over 20% experience urinary tract symptoms, with some studies reporting rates as high as 46% to 90% among heavy users. The doses and frequency used in clinical therapy are far lower than recreational use, but the risk is not zero, particularly with ongoing maintenance treatment.
The FDA has specifically warned about the risks of compounded ketamine products, particularly oral formulations and at-home ketamine prescribed through telehealth services, where monitoring is minimal or absent.
Cost and Insurance Coverage
Ketamine therapy is expensive, and paying for it remains one of the biggest barriers to access. A single IV infusion session typically costs between $400 and $800. With a standard initial course of six to eight sessions in the first month, that adds up to $2,400 to $6,400 before any maintenance sessions.
Most insurance companies still classify ketamine infusions as experimental, which means coverage is limited or nonexistent. Some plans offer partial coverage when traditional treatments have failed or when the therapy is deemed medically necessary, but this varies widely. Spravato, the FDA-approved nasal spray, has a better chance of insurance coverage precisely because of its approved status, though copays and prior authorization requirements can still make it costly. If you’re considering ketamine therapy, asking about both the per-session cost and the expected total number of sessions upfront will give you a more realistic picture of the financial commitment.
IV Ketamine vs. Spravato vs. Oral Ketamine
The three main delivery methods differ in important ways beyond just how you take them:
- IV ketamine (racemic) contains both mirror-image forms of the ketamine molecule. It’s the most studied route, produces the most consistent blood levels, and is offered off-label at specialized clinics. No FDA approval for psychiatric use.
- Spravato (esketamine nasal spray) contains only one form of the molecule. It is the only FDA-approved ketamine-related treatment for depression, must be administered in a certified healthcare setting, and is more likely to be partially covered by insurance.
- Oral ketamine is sometimes prescribed through telehealth platforms for at-home use. It has lower and more variable absorption compared to IV or nasal routes, and the FDA has raised specific safety concerns about compounded oral products used without adequate supervision.
Each route has trade-offs between convenience, cost, supervision, and how reliably the drug reaches your brain at therapeutic levels. The supervised, in-clinic options carry higher upfront costs but offer professional monitoring during a session where dissociation and blood pressure changes are expected.