Ketamine is used because it can relieve severe depression, chronic pain, and suicidal thoughts far faster than conventional treatments. Standard antidepressants take four to six weeks to reach full effect. Ketamine can produce measurable improvement within hours, and its benefits often persist for weeks after a single dose. That speed, combined with its ability to help people who haven’t responded to other medications, is why it has become one of the most significant developments in psychiatric and pain medicine.
How Ketamine Works in the Brain
Ketamine’s effects go well beyond what traditional antidepressants do. Most older medications work by adjusting levels of serotonin or norepinephrine, a process that requires weeks of daily dosing before the brain adapts. Ketamine takes a different route entirely: it blocks a specific receptor involved in how brain cells communicate, which triggers a cascade of changes in the prefrontal cortex, the region responsible for mood regulation, decision-making, and emotional processing.
When ketamine blocks these receptors on inhibitory brain cells, it releases a brake on excitatory signaling. The result is a surge of glutamate, the brain’s primary excitatory chemical messenger. That glutamate burst activates a growth-signaling pathway that rapidly increases production of a key protein called BDNF, which acts like fertilizer for neural connections. New synaptic proteins begin appearing as early as two hours after a dose, and BDNF levels remain elevated for at least 72 hours.
This process essentially helps the brain rebuild connections that depression, trauma, or chronic stress have weakened. Researchers describe it as “resetting the system” by counteracting the synaptic deficits and neuronal shrinkage that characterize depression. Unlike medications that need to be taken every day, ketamine appears to induce lasting structural changes in brain cells that sustain its therapeutic effects well beyond the time the drug is active in the body.
Treatment-Resistant Depression
The most common reason ketamine is used clinically is for depression that hasn’t responded to standard medications. Roughly one-third of people with major depression don’t improve after trying two or more antidepressants, a condition called treatment-resistant depression. For these patients, ketamine represents a fundamentally different approach.
The results can be striking. In a naturalistic follow-up study of patients receiving repeated ketamine infusions, the response rate at nine months was 80.3%, with 78.9% achieving full remission. Among those who responded to the initial treatment course, 46.4% maintained their improvement throughout the entire nine-month follow-up period. The challenge is that relapse can happen quickly once treatment stops. Of patients who did relapse, nearly 86% did so within the first two weeks after their last infusion, which is why many clinics use maintenance schedules with periodic boosters.
Rapid Reduction of Suicidal Thoughts
Perhaps ketamine’s most urgent application is in people experiencing active suicidal ideation. Standard antidepressants are essentially useless in a crisis because they need weeks to work. Ketamine closes that gap dramatically.
A meta-analysis published in Translational Psychiatry found that ketamine produced a significant reduction in suicidal thoughts within the first 24 hours after treatment. The improvement seen on day one of ketamine was comparable to what patients in placebo groups experienced after roughly 26 days of natural recovery. That compression of the timeline, from nearly a month down to a single day, is what makes ketamine valuable in acute psychiatric emergencies where waiting is not a safe option.
Chronic Pain Conditions
Ketamine is also used for severe, treatment-resistant pain, particularly complex regional pain syndrome (CRPS), a condition where the nervous system amplifies pain signals far beyond what an injury would normally produce. A systematic review found that ketamine produced greater pain score reductions in CRPS than in any other chronic pain condition studied.
The duration of relief varies considerably depending on the dosing protocol. A single infusion series can provide relief lasting anywhere from a few weeks to several months. One study found mean pain relief lasting three to six months after a single dose, with a second infusion extending that to one to three years. Another found that a five-day infusion protocol produced complete pain relief in 50% of patients with advanced CRPS, lasting at least six months. For patients whose pain has resisted every other treatment, even temporary windows of relief can be transformative.
PTSD and Anxiety
Ketamine-assisted psychotherapy has shown promising results for post-traumatic stress disorder and anxiety disorders. A large retrospective study measuring outcomes in patients treated for depression, anxiety, and PTSD found large treatment effects at three months across all three conditions, with effect sizes ranging from 0.75 to 0.86. Those improvements held at six months, with effect sizes of 0.61 to 0.73. In clinical terms, these are considered large, meaningful changes in symptom severity.
The neuroplasticity window ketamine opens may be part of why it pairs well with therapy. During the hours and days after treatment, when the brain is actively forming new connections and BDNF levels are elevated, patients may be more able to process traumatic memories and form new patterns of thinking. This is why many clinics integrate psychotherapy sessions into the days surrounding ketamine treatments rather than using the drug in isolation.
IV Ketamine vs. Nasal Spray
Ketamine is available in two main clinical forms. Intravenous (IV) racemic ketamine is the older, off-label form administered in specialized clinics. Esketamine, a nasal spray sold under the brand name Spravato, is the only form with FDA approval for treatment-resistant depression. Despite being the newer, approved option, the nasal spray is not necessarily more effective.
A systematic review and meta-analysis comparing the two found that IV ketamine showed a nonsignificant trend toward better response and remission rates. More notable was the speed difference: IV ketamine reached clinical response in a median of 2 treatments compared to 4 for the nasal spray, and reached remission in 2 treatments versus 7. One study found that 47% of IV ketamine patients responded by week one, compared to just 7% of nasal spray patients. The IV form delivers the drug with near-complete bioavailability directly into the bloodstream, while the nasal spray absorbs through the nasal lining at roughly 54% bioavailability, which likely explains the difference in onset speed.
The nasal spray does have practical advantages: no needles, a standardized fixed dose, and FDA oversight through a risk management program that requires certified clinics and at least two hours of post-dose observation. IV ketamine dosing is weight-based and follows clinic-specific protocols, with many centers discharging patients within an hour once vital signs are stable.
What a Treatment Session Looks Like
A typical IV ketamine infusion lasts about 40 minutes. You’ll have an IV line placed, and throughout the session, nurses monitor your heart rhythm, oxygen levels, and blood pressure every 15 minutes. Staff watch continuously for perceptual changes, blood pressure spikes, or any respiratory concerns.
During the infusion, many people experience dissociation: a floating sensation, altered perception of time, or visual distortions. These effects are temporary and generally resolve within an hour after the infusion ends. For depression, a standard acute course involves two to three sessions per week over a period of two to three weeks. The nasal spray follows a slightly longer schedule, typically twice weekly for four weeks. After the initial series, many patients transition to maintenance sessions spaced weeks or months apart.
Who Should Not Use Ketamine
Ketamine temporarily raises blood pressure, which means it is not appropriate for everyone. International consensus guidelines recommend excluding patients with uncontrolled hypertension (baseline blood pressure above 140/90), central aneurysmal disease, significant heart valve disease, recent heart attack, or advanced heart failure. These cardiovascular risks are manageable in most people but dangerous in those with pre-existing conditions.
Ketamine is also generally avoided in people with a history of psychotic disorders, since it can temporarily produce perceptual disturbances that could worsen psychosis. Long-term, heavy recreational use of ketamine is associated with bladder damage, but this is rarely a concern at the lower doses and limited frequency used in clinical settings.