Ketamine assisted therapy combines low doses of ketamine, a medication originally developed as an anesthetic, with psychotherapy to treat depression, PTSD, and other mental health conditions. Unlike traditional antidepressants that can take weeks to work, ketamine often produces noticeable mood improvements within hours or days. About half of patients with treatment-resistant depression respond to a course of ketamine infusions, and roughly 30% achieve full remission.
How Ketamine Works in the Brain
Standard antidepressants target serotonin or norepinephrine, but ketamine takes a completely different route. It blocks a specific type of receptor involved in glutamate signaling, the brain’s primary excitatory messaging system. This blockade triggers a cascade of effects that essentially wake up neural pathways that depression has quieted.
When ketamine blocks these receptors, it releases the brakes on production of a key growth factor (BDNF) that neurons need to form new connections. Under normal resting conditions, brain activity actively suppresses the production of this growth factor. Ketamine lifts that suppression, flooding the brain with the raw materials for building and strengthening synapses. This is why researchers describe ketamine’s effect as promoting “neuroplasticity,” the brain’s ability to rewire itself. The rapid formation of new neural connections is thought to explain why people feel relief so much faster than with conventional medications.
This same neuroplasticity window is what makes the therapy component so valuable. During and shortly after a ketamine session, the brain is more receptive to forming new thought patterns, which therapists can guide through structured psychotherapy techniques.
What a Treatment Course Looks Like
A typical initial course consists of six sessions given every other day over a 12 to 14 day period. This concentrated schedule appears to produce the best outcomes. During each session, you receive a sub-anesthetic dose of ketamine, meaning it’s far lower than what would be used in surgery. Sessions generally last between 40 minutes and a few hours depending on the method of delivery and whether psychotherapy is integrated during the experience.
Most people who respond to the initial series need ongoing maintenance sessions. The frequency varies from person to person, but once or twice a month is common. Some patients gradually extend the time between sessions as their condition stabilizes. A real-world study of 537 patients found that those who responded to the initial course had roughly an 80% chance of maintaining that improvement at four weeks and about a 60% chance at eight weeks, even without additional infusions.
Methods of Delivery
Ketamine can be administered several ways, and the method affects both the experience and the setting.
- Intravenous (IV) infusion: The most studied method for depression. A slow drip delivers ketamine directly into the bloodstream over about 40 minutes, allowing precise dose control. This is done in a clinic under medical supervision.
- Intramuscular (IM) injection: A single shot, typically in the shoulder or thigh. Onset is slightly slower than IV but still rapid. Also clinic-based.
- Nasal spray (esketamine): Sold under the brand name Spravato, this is the only form with full FDA approval for psychiatric use. It uses esketamine, a mirror-image molecule of ketamine, and is self-administered under supervision in a certified healthcare setting.
- Oral lozenges or tablets: Sometimes prescribed for at-home use between clinic sessions. Absorption through the gut is less predictable, so the experience can vary more from dose to dose.
FDA Approval and Off-Label Use
This distinction matters because it directly affects what you’ll pay and how treatment is structured. The nasal spray form (esketamine/Spravato) is FDA-approved for two specific conditions: treatment-resistant depression in adults and depressive symptoms with acute suicidal thoughts in adults with major depressive disorder. It’s classified as a Schedule III controlled substance.
IV ketamine infusions for depression, anxiety, PTSD, and chronic pain are considered off-label use. The drug itself has long been FDA-approved as an anesthetic, but its psychiatric applications through IV or other routes haven’t gone through the formal approval process for those indications. Off-label prescribing is legal and common in medicine, but it affects insurance coverage significantly.
What the Experience Feels Like
During a session, most people experience a dissociative state, a feeling of being mentally separated from your body or surroundings. This can range from mild floating sensations to more vivid perceptual changes. Some people describe it as dreamlike. Others find it disorienting, particularly during the first session. In ketamine assisted therapy specifically, a therapist is present to help you process whatever comes up during this altered state and to guide the experience therapeutically.
Common side effects during and immediately after a session include dizziness, nausea, drowsiness, and temporary increases in blood pressure. Some people feel agitated or anxious. These effects typically resolve within a couple of hours. You won’t be able to drive afterward, so plan for someone to take you home. Coordination and judgment can be impaired for the rest of the day.
More serious but less common reactions include hallucinations, significant blood pressure spikes, and in rare cases signs of liver stress. Long-term or frequent ketamine use has been linked to bladder problems, including a form of chronic cystitis that causes pain and urinary urgency. This is more associated with misuse or very high-frequency use than with supervised therapeutic protocols, but it’s worth knowing about if you’re considering long-term maintenance.
Who Is and Isn’t a Good Candidate
Ketamine assisted therapy is primarily aimed at people who haven’t responded to at least two standard antidepressants, a condition formally called treatment-resistant depression. It’s also used for PTSD, severe anxiety, and certain chronic pain conditions, though the evidence base is strongest for depression.
Several conditions rule out ketamine therapy. According to guidelines from the American Psychiatric Nurses Association, these include:
- Active substance abuse (alcohol, cannabis, or non-prescribed drugs)
- History of psychosis
- Uncontrolled high blood pressure
- Unstable cardiovascular disease
- Current pregnancy
- History of increased pressure inside the skull
- A previous negative reaction to ketamine
The substance abuse exclusion is particularly important because ketamine itself carries addiction potential. Providers will screen carefully for this before starting treatment.
Cost and Insurance Coverage
A single ketamine infusion session typically costs between $400 and $800. With a standard six-session induction course, you’re looking at $2,400 to $4,800 upfront before maintenance sessions begin. Monthly or bimonthly maintenance adds ongoing costs that can stretch into thousands of dollars per year.
Insurance coverage remains a significant barrier. Many insurers still classify ketamine therapy as experimental for mental health conditions, which means limited or no reimbursement. Some plans offer partial coverage when traditional treatments have failed and a provider documents medical necessity. The FDA-approved nasal spray (Spravato) has better insurance coverage than IV infusions since it has formal approval for psychiatric use, though copays and prior authorization requirements vary widely between plans. If cost is a concern, ask the clinic directly about payment plans and whether they’ll help with insurance appeals before committing to treatment.