Ketamine treatment uses a decades-old anesthetic drug at low doses to treat severe depression and chronic pain. Originally approved by the FDA as an anesthetic in 1970, ketamine gained attention in the early 2000s when researchers discovered that a single low-dose infusion could relieve depression symptoms within hours, a striking contrast to traditional antidepressants that take 4 to 12 weeks to work. Today, ketamine is delivered through IV infusions at specialized clinics or as a prescription nasal spray, and it represents one of the most significant shifts in how treatment-resistant depression is managed.
How Ketamine Works in the Brain
Traditional antidepressants work by adjusting levels of serotonin or norepinephrine, neurotransmitters that regulate mood. Ketamine takes a completely different route. It blocks a specific type of receptor involved in glutamate signaling, the brain’s primary excitatory chemical messenger. This blockade triggers a cascade of events: a burst of glutamate floods the synapse, which activates a chain of molecular signals that ultimately produces a protein called brain-derived neurotrophic factor (BDNF).
BDNF is essentially fertilizer for brain cells. It promotes the growth of new connections between neurons, a process called neuroplasticity, particularly in areas of the prefrontal cortex and hippocampus that are often impaired in people with depression. Ketamine has been shown to rapidly enhance the formation of dendritic spines, the tiny branches neurons use to communicate with each other. This physical rewiring of neural connections appears to be what drives the rapid mood improvement. When researchers blocked BDNF activity in animal studies, ketamine’s antidepressant effects disappeared entirely, confirming that this growth factor is central to how the drug works.
BDNF also creates a positive feedback loop: once produced, it stimulates its own receptor, which triggers further activation of the same molecular pathway, reinforcing the new neural connections. This may explain why a single infusion can produce effects lasting days to weeks beyond the drug’s presence in the body.
What Ketamine Treatment Looks Like
Ketamine treatment comes in two main forms: intravenous (IV) infusions of racemic ketamine and a nasal spray called Spravato (esketamine). The experiences differ in important ways.
IV Ketamine Infusions
The standard IV protocol uses 0.5 mg/kg of body weight infused over 40 minutes. A typical induction course involves eight infusions spread over four weeks, usually given twice per week. During each session, you sit or recline in a clinic while a provider monitors your vital signs, including heart rate, blood pressure, oxygen levels, and temperature, at regular intervals. Most people experience some degree of dissociation during the infusion: a floaty, dreamlike feeling that can range from mild detachment to a more intense altered state. These effects, along with any nausea or temporary increases in blood pressure, typically resolve within an hour to 90 minutes after the infusion ends.
IV ketamine for depression is used “off-label,” meaning clinicians prescribe an FDA-approved drug for a purpose it wasn’t specifically approved for. This is a legal and common medical practice, but it affects insurance coverage, which we’ll get to below.
Esketamine Nasal Spray
Spravato is the only FDA-approved ketamine-based treatment for psychiatric conditions. It’s approved for two specific uses: treatment-resistant depression in adults (meaning depression that hasn’t improved after trying at least two other antidepressants) and depressive symptoms in adults with major depression who have active suicidal thoughts or behavior. It must be used alongside a traditional oral antidepressant, not on its own.
Because of risks including sedation, dissociation, and the potential for misuse, Spravato is available only through a restricted safety program. You cannot take it home. Every dose must be self-administered under the direct observation of a healthcare provider in a certified treatment center, and you must be monitored for at least two hours afterward. You’ll also need to arrange a ride home, as driving isn’t safe for the rest of the day.
How Fast It Works Compared to Standard Antidepressants
Speed is ketamine’s most notable advantage. Standard antidepressants like SSRIs and SNRIs typically take 4 to 12 weeks to produce meaningful improvement, and that’s only if the patient responds at all. Ketamine can produce antidepressant effects within hours. Research from a randomized controlled trial published in the American Journal of Psychiatry found that patients given a single ketamine infusion showed significantly greater improvement in depression scores at just 24 hours compared to a control group.
This rapid onset is especially important for people in acute crisis. Weeks of waiting for a medication to take effect can be dangerous for someone experiencing suicidal ideation, which is one reason the FDA approved esketamine specifically for that population. The tradeoff is that ketamine’s effects from a single dose don’t last indefinitely. Most people need repeated sessions, initially at closer intervals and then spaced further apart for maintenance, to sustain the benefit.
Ketamine for Chronic Pain
Beyond depression, ketamine is used to treat chronic pain conditions that haven’t responded to other therapies. The dosing is similar to psychiatric protocols: 0.5 mg/kg infused over 40 minutes. However, pain protocols often use a more intensive schedule. One standardized approach involves five consecutive daily infusions rather than the twice-weekly spacing used for depression. Published protocols vary widely in dosage, frequency, and duration, ranging from single two-hour infusions to continuous multi-day treatments in inpatient settings.
Ketamine’s pain-relieving effects stem from the same receptor-blocking action that drives its antidepressant properties. By interrupting glutamate signaling, it can reduce the central sensitization that keeps chronic pain cycles going, particularly in conditions like complex regional pain syndrome. Pain applications remain off-label.
Side Effects During and After Treatment
The most common side effect is dissociation, that sense of feeling detached from your body or surroundings. This can feel unsettling if you’re not prepared for it, but it resolves predictably. In clinical monitoring, both dissociative and psychotic-like symptom scores consistently dropped to “absent” within one hour of an infusion ending.
Other common acute effects include:
- Nausea, which clinics often pretreat with anti-nausea medication
- Temporary blood pressure increases, usually mild and monitored throughout
- Dizziness or lightheadedness that fades as the drug clears
- Perceptual changes like blurred vision or sensitivity to light and sound
These side effects are well-characterized and short-lived at therapeutic doses, which is why the monitoring period exists. Clinics assess your vital signs and mental status before, during, and after each session, typically checking every 15 minutes for up to 90 minutes post-infusion.
Long-Term Safety Considerations
One concern that comes up frequently is bladder damage. Ketamine-induced cystitis is a well-documented problem among recreational users, with over 25% of people who use ketamine recreationally reporting cystitis-like symptoms. The risk is strongly tied to dose and frequency: about 20% of frequent recreational users develop bladder symptoms compared to roughly 7% of infrequent users. Regular recreational use increases cystitis risk by three to four times, and the severity of symptoms correlates directly with how much and how often someone uses the drug.
The key distinction is that therapeutic doses are far lower and less frequent than recreational use patterns. That said, long-term maintenance treatment does involve repeated exposure over months or years, and this remains an area where clinicians exercise caution and monitor for urinary symptoms. Stopping ketamine use is generally associated with improvement in bladder symptoms when they do occur.
Who Should Not Receive Ketamine
Ketamine treatment is not appropriate for everyone. Standard exclusion criteria include a diagnosis of a psychotic disorder (such as schizophrenia), active substance use disorder, uncontrolled medical conditions, cognitive decline, and pregnancy or breastfeeding. People with cardiovascular disease require careful risk-benefit evaluation, since ketamine temporarily raises blood pressure and heart rate. In patients without these contraindications, the drug is generally considered safe and well-tolerated regardless of what other psychiatric medications they’re taking.
Cost and Insurance Coverage
Cost is one of the biggest practical barriers to ketamine treatment. IV ketamine infusions typically run $400 to $800 per session out of pocket, and a full induction course of six to eight sessions can total several thousand dollars. Because IV ketamine for depression is off-label, most insurance plans do not cover it.
Esketamine (Spravato) has a different financial picture because it is FDA-approved. Many commercial insurance plans and Medicare cover it, though your actual cost depends on your specific plan’s co-pay structure, whether the certified treatment center is in-network, and whether coverage falls under your medical benefit or a separate behavioral health benefit. The manufacturer offers a savings program that may reduce out-of-pocket costs for eligible patients. Even with insurance, the required in-clinic monitoring adds facility fees that can make treatment more expensive than a standard prescription.