Written by Aisha Saleem, Pharmacist & Health Writer at PharmaHealths.com
Last Updated: July 2026
Ketamine has gone from being known primarily as an anaesthetic and a misused recreational drug to being one of the most significant developments in depression treatment in the last three decades. Today, ketamine therapy for depression is gaining attention as a fast-acting option for patients who do not respond to standard antidepressants. That transition has been accompanied by a lot of noise, extraordinary claims on one side and serious skepticism on the other, which makes it genuinely difficult for patients to get a clear picture of what ketamine therapy actually is, what it can and cannot do, and whether it might be relevant to their situation.
This article cuts through both the hype and the fear to give you an honest, evidence-based overview of ketamine therapy for depression: the real benefits, the real risks, and the myths worth dismissing.
What Is Ketamine Therapy for Depression?
Ketamine therapy for depression refers to the clinical use of ketamine or its derivative esketamine at carefully controlled doses in a supervised medical setting to produce rapid antidepressant effects.
It is most commonly used for treatment-resistant depression, defined as inadequate response to at least two antidepressants taken at the right dose and duration. It is also used in cases of major depressive disorder with acute suicidal ideation, where the speed of conventional antidepressants is clinically inadequate.
There are two main forms, and it matters that patients understand the regulatory difference between them. Intravenous ketamine infusion delivers racemic ketamine directly into the bloodstream over approximately 40 minutes in a clinic setting. It is not licensed in the UK for depression, so its use here is off label, prescribed only where a clinician judges it appropriate after individual assessment. Esketamine nasal spray, branded as Spravato, is the S-enantiomer of ketamine administered as a nasal spray in a certified healthcare setting with mandatory monitoring for at least two hours afterwards. The National Institute for Health and Care Excellence approved esketamine for treatment-resistant depression in 2022, making it the first genuinely new antidepressant mechanism approved in over 30 years and the only form of ketamine treatment with formal UK licensing for this indication.
Globally, esketamine has also been approved by the FDA in the United States and by the European Medicines Agency in Europe for treatment-resistant depression under strict risk management and monitoring programs. Access and clinical protocols vary by country, but in most regions, esketamine is administered only in certified healthcare settings with post-dose observation to ensure patient safety.
What Are the Benefits of Ketamine Therapy?
The most clinically significant benefit of ketamine therapy is speed. Unlike conventional antidepressants which require four to six weeks for therapeutic effects to develop, ketamine can produce measurable antidepressant effects within hours to days of administration.
Zarate et al., 2006, in the journal Archives of General Psychiatry, found that a single intravenous dose of ketamine produced significant symptom reduction within four hours in patients with treatment resistant depression, with peak effects at 24 hours, a timeline no conventional antidepressant can approach. Response rates of 50 to 70% have been consistently reported in treatment resistant populations across multiple trials.
Murrough et al., 2013, in the American Journal of Psychiatry, demonstrated that ketamine produced rapid and significant reductions in suicidal ideation in treatment-resistant patients, with effects emerging within 24 hours and independent of its broader antidepressant action. For patients with acute suicidal ideation, this rapid onset is not just clinically impressive, it can be life-saving.
A further benefit is mechanistic novelty. Ketamine works on the glutamate NMDA receptor pathway rather than the monoamine system targeted by conventional antidepressants. This means it can be effective in patients who have exhausted multiple serotonergic and noradrenergic medications. It is not simply a more powerful version of the same approach; it represents a genuinely different biological entry point into the treatment of depression.
What Are the Real Risks of Ketamine Therapy?
Ketamine therapy carries real risks that deserve honest discussion rather than minimization.
Dissociation is the most commonly experienced acute effect. During and shortly after an infusion or esketamine dose, patients frequently experience a sense of detachment from their surroundings, altered perception of time, and in some cases visual disturbances. These effects are dose-dependent and typically resolve within one to two hours. Around one in ten patients describe the experience as genuinely difficult rather than merely unusual, and clinics that do not prepare patients adequately for this possibility are not providing adequate care.
A less commonly discussed risk is temporary worsening. In a minority of patients, depressive symptoms and suicidal thoughts can intensify for up to two weeks after an infusion before settling, and some patients choose not to continue treatment as a result. Those who do persist often find later sessions start to help. This is exactly why every course needs close clinical follow-up in the days after treatment, not just during the session itself.
Cardiovascular effects include transient increases in blood pressure and heart rate during infusion. These are monitored throughout every session and are clinically manageable in most patients, but ketamine is contraindicated or requires specialist assessment in patients with uncontrolled hypertension, significant cardiovascular disease, or a history of stroke. At the higher doses used in anaesthesia rather than therapeutic depression treatment, rarer effects such as respiratory depression and laryngospasm have been reported, which is one reason therapeutic doses are kept well below anaesthetic ones and sessions are always medically supervised.
Nausea and dizziness are common short-term side effects that typically resolve within a few hours. Pre-treatment with an antiemetic is standard practice at reputable clinics.
Dependency and misuse potential is a legitimate concern that must be addressed transparently. Ketamine has a recognized misuse liability in recreational settings at uncontrolled doses. In clinical therapy settings, doses are precisely controlled, the drug is administered under supervision, and patients do not take ketamine home. It’s also worth separating two things that get conflated: some patients find their depression returns when ketamine treatment stops, which reflects reliance on an ongoing effect rather than addiction, while a smaller number develop tolerance over a maintenance course, needing a treatment break or a change in protocol. Regulatory bodies such as the FDA and UK authorities classify ketamine as a controlled substance, and clinical protocols are designed specifically to minimize misuse risk. A history of substance misuse disorder is a significant contraindication that must be assessed individually by the treating team.
Long term bladder toxicity is a serious risk associated with heavy recreational ketamine use and is worth mentioning in the context of maintenance therapy. Clinical doses used in therapeutic settings are substantially lower than those associated with ketamine cystitis, and there are currently no reports of bladder damage from clinically administered therapeutic ketamine at standard doses. However, patients on extended maintenance protocols should be aware of this and discuss long-term monitoring with their treating team.
Psychological vulnerability is a consideration in patients with a personal or family history of psychosis or schizophrenia spectrum disorders. Ketamine can transiently increase psychotomimetic symptoms, and these patient groups require specialist psychiatric assessment before treatment and are often excluded from ketamine therapy.
Patients should not drive, operate machinery, or make important decisions for the rest of the day after receiving ketamine treatment.
What Are the Biggest Myths About Ketamine Therapy?
Myth one: ketamine therapy is the same as taking the drug recreationally.
This is the single most persistent misconception and the one most likely to put appropriate patients off a treatment that could significantly help them. Recreational ketamine use involves uncontrolled doses, unknown purity, no medical oversight, and consumption in settings with no monitoring or safety infrastructure. Clinical ketamine therapy uses pharmaceutical-grade drug, precise dosing calibrated to body weight, continuous clinical monitoring, and a structured therapeutic protocol. The pharmacology of the drug is the same, the context, dose, safety framework, and intent are completely different.
Myth two: ketamine is a last resort only for the most extreme cases.
Ketamine is approved and indicated for treatment-resistant depression, meaning patients who have not responded to at least two antidepressants. That describes a very large number of people. It is not reserved only for the most severe psychiatric presentations and is increasingly being used earlier in the treatment pathway for appropriate patients.
Myth three: ketamine therapy provides a permanent cure.
It does not. The antidepressant effects of ketamine are time-limited. A single infusion course typically produces relief lasting days to weeks. Ongoing maintenance sessions, typically weekly or monthly, are required for sustained benefit in most patients. This is not a failure of the treatment; it is a known characteristic of its pharmacology that should be discussed explicitly before starting.
Myth four: the dissociation means you lose control or do something dangerous.
Dissociation during ketamine therapy is a pharmacological effect, it does not involve loss of consciousness, loss of memory, or inability to communicate. Patients remain responsive throughout. The experience is unusual but is not dangerous and is not comparable to being unconscious or out of control. Preparation and a calm supervised environment significantly improve how patients experience this effect.
Who Is Not Suitable for Ketamine Therapy?
Ketamine therapy is not appropriate for everyone, and a thorough pre-treatment assessment is essential. Absolute or relative contraindications include uncontrolled hypertension, active or historical psychosis or schizophrenia spectrum disorder, active substance misuse disorder, severe liver disease, pregnancy, and certain cardiovascular conditions. Any previous adverse reaction to ketamine or anaesthetic agents must be disclosed.
The assessment should include a full psychiatric history, physical health review, medication reconciliation, and a structured discussion of the patient’s expectations and concerns. Patients should leave the assessment with a clear understanding of what to expect during sessions, what the realistic treatment goals are, and what the monitoring and aftercare plan involves.
How Is Ketamine Therapy Monitored and What Does a Session Involve?
A standard IV ketamine infusion lasts approximately 40 minutes. Blood pressure, heart rate, and oxygen saturation are monitored continuously throughout. A clinician is present for the entire session. Patients are typically asked to remain in a recliner in a quiet, calm environment and are discouraged from using phones or screens during the infusion.
Esketamine nasal spray under the Spravato protocol involves the patient self-administering the spray under clinical supervision. Monitoring for at least two hours after each dose is mandatory under the NICE approved protocol, and patients must not drive on the day of treatment.
A standard initial course involves six sessions delivered over two to three weeks for IV ketamine, or twice-weekly sessions for the first month followed by weekly then monthly for esketamine. Response should be assessed formally using symptom rating scales throughout, and follow-up in the days after each session matters as much as monitoring during it, given how symptoms can shift in the immediate aftermath.
Bottom Line
Ketamine therapy offers one of the fastest-acting treatments for depression, particularly in treatment-resistant cases and suicidal crises. However, its effects are temporary, require medical supervision, and are not suitable for everyone. A careful clinical assessment is essential before considering this option.
FAQs
Q1. How quickly does ketamine therapy work for depression?
Ketamine can produce measurable antidepressant effects within hours of the first infusion, with peak effects typically at 24 hours. This is the most clinically significant distinction from conventional antidepressants, which require four to six weeks. Most patients notice meaningful change within the first two to three infusions of a standard course.
Q2. How long do the effects of ketamine therapy last?
The antidepressant effects of a single ketamine infusion typically last days to weeks. A full initial course of six infusions generally produces effects lasting weeks to months. Ongoing maintenance sessions are required for sustained benefit in most patients. The duration of response varies significantly between individuals.
Q3. Is ketamine therapy addictive?
Ketamine has misuse potential in recreational settings, but clinical therapy uses precisely controlled doses under medical supervision with no take-home supply. The risk of developing dependency through a properly administered clinical protocol is considered low. A history of substance misuse disorder is a significant contraindication that requires specialist assessment before treatment can be considered.
Q4. What does ketamine dissociation feel like?
Dissociation during a ketamine infusion is commonly described as a dreamlike detachment from surroundings, altered perception of time, and in some cases visual changes. Patients remain responsive and able to communicate throughout. The experience typically resolves within one to two hours of the infusion ending. Proper preparation by the clinical team significantly reduces distress during this phase.
Q5. Is ketamine therapy available on the NHS?
Esketamine nasal spray (Spravato) has NICE approval for treatment-resistant depression and is available through NHS England in specific clinical pathways for eligible patients. IV ketamine infusions are not currently commissioned by the NHS as a standard treatment and are primarily accessed privately. Access through NHS specialist centers varies by region.
Q6. What is the difference between IV ketamine and esketamine nasal spray?
IV ketamine delivers racemic ketamine intravenously over 40 minutes and is used off-label for depression, as it is not licensed for this indication in the UK. Esketamine nasal spray (Spravato) contains the S-enantiomer of ketamine, is self-administered under supervision, and is the only licensed and NICE-approved form for treatment-resistant depression in the UK. Both have strong evidence for rapid antidepressant effects. IV ketamine has a longer research history while esketamine has formal regulatory approval and a standardized clinical protocol.
Q7. Can ketamine therapy cause psychosis?
Ketamine can transiently increase psychotomimetic symptoms at higher doses, which is why a personal or family history of psychosis or schizophrenia spectrum disorder is a significant contraindication requiring specialist assessment. At therapeutic doses in appropriately selected patients, clinically significant psychotic symptoms are not an expected outcome. The dissociative effects experienced during treatment are distinct from psychosis.
Call to Action
If you’re considering ketamine therapy or trying to understand whether it might be relevant to your situation, the mental health section at PharmaHealths.com has everything you need alongside this guide. I’ve written a detailed comparison of TMS and ketamine therapy for treatment-resistant depression, a deep dive into how ketamine works on the NMDA receptor pathway, a step-by-step patient guide to TMS therapy, and a complete overview of all brain stimulation therapies available for depression. All written from a pharmacist’s perspective, evidence-based, clearly explained, and designed to help you have more informed conversations with your clinical team.
Disclaimer
This article is for general informational and educational purposes only and does not constitute medical advice or a treatment recommendation. Ketamine and esketamine are controlled substances and specialist medical treatments that must be assessed, prescribed, and supervised by qualified healthcare professionals. Individual eligibility, risks, and clinical suitability vary significantly. Always consult your GP, psychiatrist, or specialist team before making any decisions about your treatment.
References
• Zarate CA Jr et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry. 2006. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/209553
• Murrough JW et al. Antidepressant efficacy of ketamine in treatment-resistant major depression. American Journal of Psychiatry. 2013. https://ajp.psychiatryonline.
