What Type of Drug Is Ketamine? 

Ketamine’s Official Medical Classification

The U.S. Food and Drug Administration (FDA) first approved ketamine in 1970 for anesthetic use, and the Drug Enforcement Administration (DEA) classifies it as a Schedule III controlled substance, recognizing its medical utility and potential risks. It is on the World Health Organization's (WHO) list of 100 most essential medications for health systems globally, and is one of the most commonly used drugs in surgeries such as c-sections for anesthesia. It was originally FDA approved “on label” for anesthesia and analgesia back in 1970, and has been generic (off patent) since 2002. Because ketamine was FDA approved for anesthesia, it can be used “off-label” for other indications.

Ketamine’s antidepressant effects were first noticed over 25 years ago, and since then, it has been the most studied drug for the treatment of depression (Namiat et al, 2024). Clinical studies and real‑world experience continue to support its rapid impact on mood, suggesting that ketamine is a safe and effective treatment for depression when administered in a medically supervised way (Carreno et al. 2020).

When used for depression, ketamine is considered “off‑label”, meaning the FDA hasn’t explicitly approved it for mood disorders. But off-label medication prescribing is common and medically accepted,  especially in psychiatry. Studies have shown that many psychotropic medications are used off-label, and clinicians often base these decisions on emerging evidence and patient need (Vijay et al. 2018). In mental health, over 60% of medications prescribed are off-label. Nearly all of these medications are covered by insurance for those off-label uses (Chen et al. 2006).

Although ketamine is chemically the same whether used in anesthesia or for depression, the context of use matters deeply: lower doses, in-clinic monitoring, and therapeutic intent all shape safety and efficacy. At Ember Health, our IV ketamine protocol is part of a coordinated mental health care plan. We’ve treated over 2,500 patients, 84% of whom have experienced relief from their depressive symptoms. While many people experience meaningful benefits, individual response varies.

How Ketamine Works for Depression

Ketamine works differently from traditional antidepressants. Instead of primarily targeting serotonin, it acts on the glutamate system, which is central to learning, memory, and mood regulation. Its effects can be understood through three complementary mechanisms: biologic, experiential, and neuroplastic.

Biologic Mechanisms

In plain language, ketamine helps the brain “rewire” itself in ways that support improved mood and cognitive function.

Ketamine blocks the NMDA receptor, which triggers a cascade of brain activity: a burst of glutamate release activates AMPA receptors, increases brain-derived neurotrophic factor (BDNF), and stimulates the mTOR signaling pathway. Together, these changes promote synaptogenesis (the formation of new neural connections) especially in areas like the prefrontal cortex, which are often impaired in depression ( (Abdallah et al. 2016); (Duman et al. 2012). 

Experiential Mechanisms

During an infusion, patients may feel a temporary altered state of consciousness, often described as dissociative. This is carefully monitored by clinicians and usually resolves before leaving the clinic. The thoughts and feelings that arise during the infusion experience vary widely from person to person and session to session, and may help patients approach their thoughts and emotions in a new way, supporting the therapeutic process.

Neuroplastic Mechanisms

After treatment, the brain enters a window of heightened neuroplasticity, a period when it is more capable of change. This can last for several days, creating an opportunity to reinforce positive behavioral changes, practice new coping strategies, or engage in therapy. Research suggests that combining ketamine with mental health support during this window may help make its benefits more durable (Gerhard et al. 2016).

How Ketamine Compares to Other Drugs Used for Depression

Ketamine isn't the only option for treating depression, but it works differently than most alternatives. Understanding these differences can help you and your care team determine the best approach for your situation.

Compared to SSRIs

Ketamine and SSRIs are based on different theories of how best to address depression. SSRIs are based on the “chemical imbalance” theory that depressive brains lack sufficient serotonin, and therefore, introduce a heightened exposure to serotonin via daily consumption of prescribed medications. SSRIs have shown to relieve depression in ~30% patients and take multiple weeks to take effect, often with unwanted side-effects. (Pigott et all, 2023)

Ketamine is based on the neural network theory of depression, supported by recent MRI scan imaging that shows less neural density and activity in parts of the brain that regulate emotion in depressive patients. Ketamine works through glutamate system, and exposure to the drug prompts neural regrowth and synaptic reconnections in the brain, resulting in a “reset” of the emotional reward system. IV ketamine shows an efficacy of 75% relief of depression in patients. (Nikolin et al, 2023). Though both can be part of a treatment plan, they operate through very different biological systems.

Compared to Psychedelics (Psilocybin, MDMA)

While ketamine is sometimes grouped with “psychedelics” due to the altered state of consciousness during the time of infusion, it is not officially classified as one. Ketamine infusions are relatively short (around 40 minutes), more predictable, and delivered in a medical setting. By contrast, psilocybin or MDMA sessions often last hours and are still largely investigational. In a recent study, psilocybin was found to be ~40% effective for depression (Goodwin et al, 2022). Both types of treatments may share some effects on neuroplasticity, but ketamine has an especially well-developed evidence base for depression.

Ketamine’s Regulatory Context and Future FDA Status

Despite the safety and efficacy profile of IV ketamine for depression, an FDA “on-label” approval for depression is unlikely. This is because ketamine is a generic drug, and there is no clear regulatory pathway to add a new indication to a generic drug. FDA modification would require a New Drug Application, a very costly process which is often pursued by pharmaceutical companies in the pursuit of releasing new patents, but a process that does not have precedence for drugs that are already generic. Beyond ketamine, the FDA in its history has never issued a new indication for a generic drug since it was first founded in 1906. Insurance coverage decisions for off-label use are therefore handled individually by insurance providers (Sahragardjoonegani et al.  2021).

Esketamine (Spravato), a ketamine derivative, is an FDA-approved treatment for depression: Approved in 2019 for treatment-resistant depression, Spravato is administered under strict medical supervision with REMS monitoring for safety. With that said, Spravato has a 30-40% efficacy rate for depression (compared to 75% for IV ketamine), and requires far more frequent exposure (often administered weekly) than IV ketamine treatment, where patients typically require a booster session once every six weeks to maintain benefits.

Despite not having a path for on-label approval for generic ketamine, in October 2023, the FDA issued a public alert highlighting the risks of compounded ketamine products (oral, nasal, sublingual) used for psychiatric purposes, emphasizing that ketamine for psychiatric mental health purposes should only be administered in a safe, medically monitored setting, by experienced clinicians who are working only with FDA-approved ketamine versus compounded ketamine.

It’s important to note that off-label use of medications is extremely common in mental health and evidence-supported. Nearly 60% of all medications used to treat depression are prescribed off-label. Even though ketamine for depression remains off-label, it is backed by extensive clinical research and professional consensus for treatment-resistant cases. This is consistent with standard medical practice, where off-label prescribing is routine when supported by evidence.

Professional and institutional guidance
Beyond the FDA, several regulatory and industry bodies have released consensus guidelines and statements on the safe use of ketamine for depression: 

• VA/DoD: Acknowledges ketamine/esketamine as an option for treatment-resistant depression, but emphasizes caution and use within research or specialized protocols.
  
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• APA: First mover in consensus making for ketamine’s antidepressant effects back in 2017, but has not issued updated guidelines since that time.
  
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• ASKP: Provides professional networking and practice guidance, with a peer-reviewed consensus statement on using IV ketamine for depression due out in early 2026.
  
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• UpToDate: Discusses ketamine in clinical summaries, and provides pathways on when to consider treatment, and how to provide treatment in individuals dealing with depression.
  
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Bottom line: Ketamine for depression is medically legal, evidence-supported, and professionally recognized as a viable treatment option for those in need.

Medical vs. Recreational Ketamine: Why Context Matters

While IV ketamine is a safe, effective drug to treat depression, it can also be abused when used recreationally. Headlines around ketamine highlighting misuse, dependence, or cognitive effects can understandably raise concern. However, the way ketamine is used in a medical context is fundamentally different from non-medical use, and these differences matter for both safety and effectiveness.

Understanding the differences between medical and recreational ketamine is essential for evaluating the drug’s impact on the brain and overall safety profile.

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Sources: Ember Health clinical protocols; FDA Safety Communications (2023); Marcantoni et al., Journal of Affective Disorders (2020)

The risks and benefits look very different in a clinic than in non-medical use. At Ember Health, every infusion is supervised by trained clinicians, and safety is our top priority.

Who Should Consider IV Ketamine Therapy

At Ember, we work with patients who have an active diagnosis of depression and are working with at least one licensed mental health provider (Psychiatrist, therapist, PCP, psyche NP, etc.) We can recommend trusted partners from our extensive provider network for people who are not currently working with a mental health provider.

Ketamine may be used earlier in treatment for patients with severe or high-risk symptoms, but it’s not right for everyone. It's generally not appropriate for people with a history of untreated psychosis or certain medical conditions (e.g., uncontrolled cardiovascular issues). Ember Health requires a thorough intake process to ensure ketamine therapy is safe and well-aligned with existing treatment plans.

The Ember Health Approach

At Ember Health, our care model is built on three pillars designed to make ketamine treatment safe, effective, and personalized:

1. Evidence-Based
We specialize in IV ketamine, the route of administration with the strongest safety and efficacy data. Over the past 7 years, we’ve safely administered 40,000+ infusions to 2,500+ patients across 5 clinics, achieving an 84% success rate. Every infusion follows rigorous medical protocols to ensure adherence to best practices and optimal outcomes.

2. Patient-Centered
Infusions are delivered in a calm, supportive environment by emergency medicine–trained physicians at a 1:1 patient-to-clinician ratio. Care is fully individualized, including pre-infusion planning, real-time monitoring, and post-infusion support tailored to each patient’s comfort, needs, and goals.

3. Partner-Oriented
We complement, not replace, your existing mental health care team. By collaborating with psychiatrists, therapists, and other providers, we maximize benefits during the neuroplastic window after infusion, when the brain is most receptive to therapeutic interventions, and help integrate ketamine treatment into a broader, coordinated care plan.

Making an Informed Decision

Here are some key takeaways to help you determine if ketamine therapy might be right for you:

• Off-label but well-supported
  Ketamine for depression is considered off-label, meaning it was FDA-approved originally for a different use (anesthesia). Off-label prescribing is a common, long-standing practice in medicine. IV ketamine’s use for treatment-resistant depression is supported by extensive clinical research and endorsed by major professional organizations in psychiatry, reflecting strong evidence for safety and efficacy.
• Works differently from traditional antidepressants
  Unlike SSRIs or SNRIs, which primarily target serotonin or norepinephrine, ketamine acts on the glutamate system and promotes neuroplasticity. This different mechanism helps explain its rapid antidepressant effects and its ability to address symptoms like hopelessness and anhedonia when other treatments have not worked.
• Medically supervised care is essential
  While ketamine is increasingly available in oral or compounded forms, these carry higher variability in dosing, absorption, and safety. In-clinic, medically supervised IV infusions provide the safest, most evidence-aligned approach, with precise dosing, real-time monitoring, and structured post-infusion support.
• Individualized assessment matters
  Responses to ketamine vary from person to person. A complimentary consultation with an Ember physician allows you to review your medical history, current treatment plan, and goals to determine whether ketamine is appropriate and how it can best be integrated into your overall mental health care strategy.

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Disclaimer: This information is for educational purposes only and does replace medical advice. Ketamine for depression is an off‑label use of an FDA-approved medication. Ember Health requires patients to work with a licensed mental health provider. Treatment outcomes vary by individual; some patients experience meaningful relief, while others may not. All infusions at Ember are administered under medical supervision with a 1:1 patient‑to‑clinician ratio.