Ketamine therapy uses low doses of ketamine, a long-established anesthetic, to treat severe depression and certain chronic pain conditions. Unlike traditional antidepressants that can take weeks to work, ketamine can produce noticeable mood improvements within hours to days of the first session. It’s typically delivered as an IV infusion in a clinical setting, though a nasal spray version called esketamine (brand name Spravato) is also available for treatment-resistant depression.
How Ketamine Works in the Brain
Traditional antidepressants target serotonin or norepinephrine, two chemical messengers involved in mood regulation. Ketamine takes a completely different route. It blocks a receptor called NMDA, which is part of the brain’s glutamate system. Glutamate is the brain’s primary excitatory chemical, and when ketamine temporarily blocks its normal signaling pathway, it triggers a cascade that increases the brain’s ability to form new neural connections.
This process, broadly called neuroplasticity, is thought to be why ketamine works so quickly. Rather than slowly adjusting chemical levels over weeks the way an SSRI does, ketamine essentially helps the brain rewire around the patterns that sustain depression. The speed of this effect is what makes ketamine particularly valuable for people in acute crisis or those who haven’t responded to other treatments.
What Ketamine Therapy Treats
The FDA approved ketamine decades ago as an anesthetic for surgical procedures. Its use for depression, anxiety, PTSD, and chronic pain is considered “off-label,” meaning doctors prescribe it based on clinical evidence even though it hasn’t gone through the formal FDA approval process for those specific conditions. Off-label prescribing is legal and common across medicine.
Esketamine, the nasal spray version, does have FDA approval specifically for treatment-resistant depression and depressive symptoms in adults with suicidal thoughts. The distinction matters mainly for insurance coverage, which we’ll get to below.
How Sessions Work
The most common delivery method is an IV infusion, where ketamine is slowly dripped into your bloodstream over about 40 minutes. You sit in a reclining chair, often with an eye mask and headphones, in a clinical setting with medical staff monitoring your vitals. The experience typically involves feeling dissociated from your body, a floating sensation, and sometimes visual disturbances. Most people describe it as dreamlike rather than unpleasant.
A standard induction phase involves six to eight sessions, often scheduled two to three times per week. After this initial round, you move into a maintenance phase where sessions are spaced further apart, typically every three weeks or so. The antidepressant effects of the first few infusions may only last one to ten days, but after completing the full induction phase, the relief from each session generally extends to about three weeks.
Other delivery methods exist but absorb less of the drug. Oral ketamine has a bioavailability of only 8% to 17% because your liver breaks most of it down before it reaches your brain. Lozenges placed under the tongue do slightly better at about 29%. The nasal spray version (esketamine) is administered in a clinic under direct supervision, and you’re required to stay for at least two hours of monitoring afterward before you can leave.
Side Effects During and After Treatment
Most side effects happen during the session itself and fade within a couple of hours. The most common ones are dizziness, nausea, a temporary increase in blood pressure, drowsiness, and feelings of dissociation or confusion. Some people experience anxiety or restlessness during the infusion. Hallucinations can occur, though they’re less common at the low doses used for mental health treatment.
The blood pressure increase is why your vitals are monitored throughout. For most people it’s modest and temporary, but it’s a meaningful concern for anyone with cardiovascular issues. Long-term, frequent ketamine use has been linked to bladder problems and liver stress, which is one reason clinicians space maintenance sessions as far apart as possible while still maintaining the therapeutic benefit.
Who Should Not Receive Ketamine
Several conditions disqualify you from ketamine therapy. According to guidelines from the American Psychiatric Nurses Association, the main exclusions are:
- Active substance abuse of any kind, including alcohol and cannabis
- History of psychosis, since ketamine’s dissociative effects can worsen psychotic symptoms
- Uncontrolled high blood pressure or unstable cardiovascular disease
- Current pregnancy
- Increased intracranial pressure
- Previous negative reaction to ketamine
Before starting treatment, clinics typically run a screening that includes your psychiatric history, current medications, blood pressure readings, and substance use history.
Cost and Insurance Coverage
This is where the distinction between IV ketamine and esketamine matters most. IV ketamine infusions for mental health are almost never covered by insurance because the treatment is off-label. Most clinics charge $400 to $800 per infusion, meaning a full induction phase of six to eight sessions can run $2,400 to $6,400 out of pocket. If the clinic includes psychotherapy alongside the infusion, that’s often billed separately at a similar rate.
There are a few exceptions. Blue Cross Blue Shield of Massachusetts covers IV ketamine for depression using criteria similar to their esketamine policy, and Kaiser Permanente in the San Francisco Bay Area offers some coverage. But these remain outliers nationally.
Esketamine (Spravato) is a different story. Most major commercial and government insurance plans cover it. If your clinic is in-network, you’ll typically owe a standard office visit copay of $30 to $50 per session. The catch is that esketamine has stricter requirements: it can only be administered in a certified healthcare setting, must be given under direct observation by a healthcare provider, and cannot be dispensed for home use. Each visit includes a mandatory two-hour monitoring period, so plan for a half-day commitment per session.
What to Expect From Results
Ketamine is not a cure. It’s a tool that can break the cycle of severe depression long enough for other treatments, like therapy and lifestyle changes, to gain traction. Some people experience dramatic improvement after a single infusion. Others need the full induction series before noticing a shift. A meaningful percentage of people don’t respond at all, though exact response rates vary across studies and patient populations.
The effects are also temporary without ongoing maintenance. Once you complete the induction phase and find that ketamine works for you, you’ll likely need periodic booster sessions to sustain the benefit. How often varies from person to person. Some people do well with a session every three to four weeks, while others can stretch to every few months. The goal is always to find the longest interval that still keeps symptoms at bay.