Ketamine is FDA approved, but only for one specific use: anesthesia. The injectable form, branded as Ketalar, was approved in 1970 and remains the only form of racemic ketamine with FDA approval. It is not FDA approved for depression, chronic pain, PTSD, or any psychiatric condition. A closely related drug called esketamine (Spravato) has a separate FDA approval for treatment-resistant depression, but it is a different product with different rules. Understanding these distinctions matters because ketamine is now widely used off-label, and the gap between what’s approved and what’s marketed to patients is significant.
What Ketamine Is Approved For
Ketamine was originally developed as an anesthetic and first approved by the FDA in 1970 under the brand name Ketalar. That approval covers injectable ketamine for use in surgical and diagnostic procedures. It is also approved for veterinary anesthesia. This remains ketamine’s only FDA-approved indication more than 50 years later.
No oral, sublingual, or lozenge form of ketamine has ever received FDA approval for any condition. The tablets, troches, and nasal sprays you may see marketed through telehealth platforms and compounding pharmacies are compounded products, meaning the FDA has not evaluated their safety, effectiveness, or quality.
Esketamine: The FDA-Approved Depression Treatment
In 2019, the FDA approved Spravato (esketamine), a nasal spray, for treatment-resistant depression in adults. Esketamine is one half of the ketamine molecule (the S-enantiomer), and while it’s chemically related to ketamine, it went through its own clinical trial process and has its own approval.
To qualify for Spravato, a patient must have tried at least two different oral antidepressants at adequate doses for at least six weeks each without meaningful improvement. The approval also covers major depressive disorder with suicidal thoughts or behavior.
Spravato comes with unusually strict oversight. The FDA requires it to be administered only in certified healthcare settings under a program called REMS (Risk Evaluation and Mitigation Strategy). A healthcare provider must directly observe the patient take the nasal spray, then monitor them for a minimum of two hours afterward, checking for sedation, dissociation, and changes in blood pressure and heart rate. The healthcare setting itself must be enrolled and certified, and staff must complete specific training. You cannot take Spravato home.
Off-Label Ketamine Use Is Common
Despite having only an anesthesia approval, ketamine is prescribed off-label for a wide range of conditions. Off-label prescribing is legal in the U.S. and common across medicine, but it means the FDA hasn’t formally reviewed whether ketamine works or is safe for these uses.
The most common off-label applications include chronic pain conditions like complex regional pain syndrome (CRPS), neuropathic pain, fibromyalgia, and chronic headaches. Ketamine is also used off-label for depression, PTSD, and post-surgical pain. For chronic pain, six meta-analyses published since 2019 report reductions in pain scores after ketamine treatment, with effects lasting from 48 hours to one month depending on the study. Across 41 randomized controlled trials, intravenous ketamine showed the most consistent results, while oral and topical forms produced mixed outcomes.
For depression, intravenous ketamine clinics have proliferated across the country, typically offering a series of infusions. These clinics operate legally through off-label prescribing, but the FDA has not established safe or effective dosing for any psychiatric use of ketamine.
How Ketamine Works Differently
Traditional antidepressants target serotonin or norepinephrine and can take weeks to produce noticeable effects. Ketamine works through an entirely different pathway. It blocks a receptor involved in communication between brain cells, which triggers a cascade of changes: strengthening connections between neurons, boosting the growth of new synaptic connections, and increasing levels of a protein that supports brain cell health and plasticity.
What’s unusual is that ketamine’s antidepressant effects outlast its physical presence in the brain. The drug is cleared relatively quickly, but the downstream changes to brain circuitry persist longer. Some research suggests a ketamine metabolite, rather than ketamine itself, may be responsible for mood-related effects, though this is still being investigated.
Compounded Ketamine Carries Extra Risk
The FDA issued a specific warning about compounded ketamine products, particularly the oral and sublingual formulations sold through telehealth companies and compounding pharmacies for psychiatric use. These products are not FDA approved for any indication, and the FDA has not reviewed their safety, effectiveness, or manufacturing quality.
The core concern is unsupervised use. When ketamine is given in a clinical setting, providers monitor for sedation, dissociation, breathing problems, and spikes in blood pressure. At-home use removes that safety net. In April 2023, the FDA reported a case where a patient taking compounded oral ketamine at home for PTSD experienced dangerously slowed breathing, with blood levels reaching twice what is typically seen during anesthesia.
Dosing inconsistency adds another layer of risk. Compounded products vary in concentration and formulation between pharmacies and even between batches, making it difficult to predict side effects. The FDA also noted that because compounded ketamine products are not part of the REMS program that governs Spravato, they lack the mandatory monitoring requirements. The agency stated this does not make them safer; it may make them less safe.
Known Side Effects
The well-documented side effects of ketamine include sedation, dissociation (a feeling of disconnection from your body or surroundings), elevated blood pressure, nausea, and respiratory depression at higher doses. Abuse and misuse are recognized risks, and ketamine is classified as a controlled substance.
One longer-term concern is bladder damage. Ketamine-induced cystitis causes symptoms like frequent urination, urgency, pain during urination, and blood in the urine. Among recreational users, over 25% report urinary symptoms, with frequent users experiencing cystitis-like symptoms at three times the rate of infrequent users. People who use ketamine have urinary tract symptoms at roughly six times the rate of the general population. While recreational use involves higher and more frequent doses than clinical treatment, bladder effects have also been reported in therapeutic settings, especially with repeated or prolonged use.
The Bottom Line on Approval
Racemic ketamine has one FDA approval: as an injectable anesthetic, granted in 1970. Esketamine (Spravato) has a separate approval for treatment-resistant depression and must be administered in a certified clinical setting with two hours of post-dose monitoring. Every other use of ketamine, including IV infusions for depression, at-home lozenges for anxiety, and infusions for chronic pain, is off-label. The FDA has explicitly stated it has not established safe or effective doses of ketamine for any psychiatric condition.