Ketamine is prescribed primarily for treatment-resistant depression, meaning depression that hasn’t improved after trying other antidepressants. It’s also used for acute pain management, certain chronic pain conditions, and increasingly for PTSD and suicidal crises. What makes ketamine unusual is how fast it works: while traditional antidepressants take weeks to kick in, ketamine can produce noticeable mood improvements within hours.
Treatment-Resistant Depression
The most common psychiatric reason ketamine is prescribed today is depression that hasn’t responded to standard medications. A nasal spray form called esketamine (brand name Spravato) is FDA-approved specifically for treatment-resistant depression in adults, either on its own or alongside an oral antidepressant. It’s also approved for adults with major depressive disorder who are experiencing acute suicidal thoughts or behavior.
The clinical evidence is substantial. In a trial of 403 patients, 55% of those who received ketamine had at least a 50% improvement in their self-reported depressive symptoms, and that improvement held throughout a six-month follow-up period. For comparison, 41% of patients receiving electroconvulsive therapy (ECT), long considered the gold standard for severe depression, achieved the same level of improvement. That trial, led by Massachusetts General Brigham researchers, also found ketamine treatment came without major side effects for most patients.
How Ketamine Works Differently From Other Antidepressants
Traditional antidepressants target serotonin, norepinephrine, or dopamine. Ketamine takes a completely different route. It blocks a receptor in the brain called the NMDA receptor, which is involved in how brain cells communicate using a chemical messenger called glutamate. By blocking this receptor on certain inhibitory brain cells, ketamine essentially releases the brakes on signaling in the prefrontal cortex, the region responsible for mood regulation, decision-making, and emotional processing.
This burst of signaling triggers a cascade of effects. It increases the release of a protein called BDNF, which acts like fertilizer for brain cells. BDNF promotes the growth of new connections between neurons, a process called neuroplasticity. In people with chronic depression, these neural connections are often weakened or lost. Ketamine appears to help rebuild them, which may explain why its effects can last days or weeks beyond the actual treatment session, even though the drug itself clears the body within hours.
Acute Suicidal Ideation
One of the most striking applications of ketamine is in psychiatric emergencies involving severe suicidal thoughts. In a double-blind, placebo-controlled trial, 43.8% of patients experienced complete remission of suicidal thinking just two hours after a single ketamine infusion, compared to only 7.3% in the placebo group. The effect appeared as early as 40 minutes after the infusion began and persisted over a three-day observation period.
This speed matters enormously in crisis situations where the window between suicidal ideation and action can be dangerously short. That said, the FDA has been careful to note that esketamine has not been proven to prevent suicide itself, and its use doesn’t replace the need for hospitalization when that’s clinically appropriate.
PTSD
Ketamine is not FDA-approved for post-traumatic stress disorder, but it’s increasingly prescribed off-label for this purpose. A randomized clinical trial of 41 patients with chronic PTSD found that a single ketamine infusion produced a significant and rapid reduction in PTSD symptom severity within 24 hours, compared to an active placebo. Patients also experienced improvements in co-occurring depressive symptoms and overall clinical presentation. The treatment was generally well tolerated, without lasting dissociative side effects.
This remains an area where evidence is building but not yet definitive. Most studies have been small, and questions about optimal dosing schedules and long-term outcomes are still being worked out.
Chronic Pain Conditions
Ketamine was originally developed as an anesthetic in the 1960s, and pain management remains one of its core uses. It’s prescribed for complex regional pain syndrome (CRPS), a condition that causes severe, persistent pain usually in a limb, often after an injury. Clinical guidelines give ketamine a moderate level of evidence for CRPS, noting that infusion protocols lasting 4 to 10 days can reduce pain for up to 12 weeks.
It’s also used in hospital and emergency settings for acute pain from trauma, burns, or surgical procedures. At lower doses, ketamine provides strong pain relief without suppressing breathing the way opioids do, which makes it particularly useful for patients who can’t tolerate opioids or who are at risk for opioid-related complications.
How Ketamine Is Given
The route of administration depends on what ketamine is being used for. The FDA-approved nasal spray (esketamine) is used in psychiatric settings for depression and must be administered in a certified healthcare facility. You can’t take it home. After each dose, you’re monitored for at least two hours because of potential side effects like dissociation, dizziness, and sedation.
For pain management and off-label psychiatric uses, ketamine is most often given as an intravenous (IV) infusion. A typical session for depression lasts about 40 minutes, while pain-focused infusions can run for several hours over multiple days. Intramuscular injections are another option, particularly in emergency and pre-hospital settings where IV access isn’t immediately available. Intranasal delivery (distinct from the branded esketamine product) is occasionally used as well.
Regardless of the route, ketamine treatment requires medical supervision. The dissociative state it produces can make it difficult to assess a patient’s neurological status, and when combined with sedatives or alcohol, it can suppress breathing. Monitoring typically includes tracking vital signs and, in higher-dose settings, watching for early signs of airway complications.
Side Effects and Risks
At the doses used for depression and pain, ketamine’s most common side effects are temporary. Dissociation (a feeling of detachment from your body or surroundings), dizziness, nausea, and increased blood pressure are typical during and shortly after treatment. These effects usually resolve within a couple of hours.
The bigger concern is with repeated or long-term use. Ketamine can affect the bladder, causing symptoms like urinary urgency, frequency, pain, and in severe cases, blood in the urine. This condition, sometimes called ketamine uropathy, has been documented primarily in people who misuse ketamine at high doses, but clinicians monitor for these symptoms in patients receiving repeated medical treatments as well. A staging system used by urologists categorizes risk by weekly exposure: under 1 gram per week is considered the lowest tier, while over 2 grams per week poses the highest risk for bladder damage.
There’s also the question of psychological dependence. Ketamine is a Schedule III controlled substance, and its dissociative properties can be psychologically appealing to some patients. Treatment protocols are designed with this in mind, spacing sessions out and limiting the total course of treatment when possible.