An individual who is experiencing resistant depression, ketamine is the best choice for them. In certain individuals, the antidepressant effects of ketamine have been reported to be very rapid and severe; however, ketamine should not be used to treat depression. It’s also not the same drug as esketamine, which has been prescribed in the UK for treatment-resistant depression.
Getting in the UK may be complicated. Ketamine has not been approved to treat depression, but doctors might prescribe it “off-label” in specialized settings. Esketamine is approved for use in a specific group of adults only and is not recommended at present for general use in the NHS.
Why Ketamine Is Being Studied for Depression
Most antidepressant drugs act on neurotransmitter changes, primarily serotonin and noradrenaline. Ketamine, on the other hand, affects the brain’s glutamate system and NMDA receptors. In the last 20 years, studies have examined the possibility of accelerating the decrease of depressive symptoms compared with some standard antidepressant medications. Some clinical studies have reported antidepressant activity in individuals who are treatment resistant to antidepressant treatment.
But, the answer is different for each person. There is also uncertainty regarding the duration of the effects of treatment, who would seem to benefit and how treatment can be maintained safely.
What Treatment-Resistant Depression Means
In many cases, treatment-resistant depression may indicate depression that remains resistant to an adequate trial of an antidepressant medication. Depending on the context, the term may have different definitions in clinical research vs. services.
For instance, according to the current product label for Spravato, the drug is indicated for adult patients who have not responded to two or more different antidepressant treatments in the last period of moderate to severe depression.
It’s important to note, however, that it isn’t a person who has just had a bad experience with one antidepressant. Doctors typically take into account the diagnosis and past treatment plan, strictness of adherence, dosage of treatment, or length of treatment, or other factors that might contribute to the ongoing symptoms.
A specialist may also review the person’s psychological treatment, their physical condition, other medications as well as their broader situation prior to recommending a treatment like ketamine/esketamine.
Is Ketamine Licensed for Depression?
Ketamine is not directly prescribed for the UK in the treatment of depression. It is known to be medically used as anaesthesia and pain killer. It also is subject of Controlled Substance in the UK. According to the 2026 ACMD review, ketamine is still a Class B controlled substance.
In some cases physicians may issue a prescription for a medication that is not indicated for the purpose it is being used for, when it is within their scope of practice to do so. This is referred to as off-label use.
Under psychiatric supervision there are some specialist NHS services that use ketamine for treating people in a very tough situation who have depression that doesn’t respond well to existing treatment. Oxford Health NHS Foundation Trust, for instance, states that they make the ketamine treatments for depression “an off label use” and run their service under specialist psychiatric supervision.
There is thus a difference between having a licence and using a drug for clinical purposes. A medicine can have a recognised medical use but be used for purposes other than those licensed.
What Does Off-Label Treatment Mean?
A medicine may be used outside the scope of its marketing authorisation if this type of medicine is used for a purpose other than what it has been authorised for. This may involve the condition being treated, patient’s age, dose or something else related to its use.
It does not automatically mean that the treatment is experimental or inappropriate. Use of drugs for purposes other than the approved indication is permitted if justified on an individual clinical basis.
The use of a medication off-label also requires medical foresight. The doctor might think about the evidence, the pros, cons and other choices. Patients should also be aware of the reason why the medicine is being considered, and the information about the medicine.
This is important in the context of ketamine’s licensed uses, particularly regarding depression, as they are different from its non-licensed uses in a specialist psychiatric setting.
What Is Esketamine?
Esketamine has the same structure as ketamine. Ketamine comes in two enantiomers (mirror-image forms). The S-enantiomer is known as esketamine. The nasal spray has been approved in the UK under the name Spravato. The product description says it is indicated, in combination with an SSRI or SNRI, in adults for the treatment of major depressive disorder who have failed to respond to at least two antidepressant medications in the current depressive episode and who have treatment-resistant depression.
Esketamine shouldn’t just be considered another form of ketamine. Both are related medicines, but not exactly the same medicines used in the same ways which are governed by different regulators.
This aspect is important to highlight in the context of access information in the UK. A licensed medicine is not routinely available on the NHS, nor is an off-label medicine regulated under the same indication as a licensed medicine.
NHS Access
However, it is not consistent throughout the UK on the NHS that a person will be able to access ketamine as a treatment for depression. Specialist services may have their own referral requirements, eligibility criteria and funding arrangements.
At this time NICE does not consider esketamine nasal spray as a treatment option for people with treatment-resistant depression. It has guidance that claims the treatment is not a cost effective use of NHS resources with substantial uncertainties recorded regarding both clinical evidence and costs. This does not indicate that esketamine is always offered on the NHS through a UK licence.
There are some specialist NHS centres that offer ketamine treatment for a number of restricted situations. Oxford Health, for instance, explains they offer specialist help for patients struggling with treatment-resistant depression and explain how they refer to and fund patients.
People who think about it need to consult with their GP or psychiatrist and not expect that all NHS mental health services offer treatment using ketamine.
Private Treatment
Depending on the clinical services and prescribing practices, private clinics might have ketamine or esketamine therapy for treating depression. Even if there is a treatment available on the private market, it is not necessarily advisable for someone with depression and not everyone will reap the benefits.
Before treatment, the correlation must go through a suitable clinical evaluation. This may involve a review of diagnosis, treatment, physical health, existing medications’ effect on mental health and risks, and physical health.
Patients could also inquire what medication they will be receiving. It’s important to understand that Ketamine and esketamine are not exactly the same, so using them interchangeably can lead to a bit of confusion.
Private treatment may also incur high costs and ongoing needs as well. If a person is thinking about this option, they will be required to be provided with clear information on the benefits of this option, the possible disadvantages of this option, the monitoring involved and what will happen if it doesn’t work.
What the Research Does and Does Not Show
There is evidence that ketamine and esketamine may help improve depression symptoms in some treatment-resistant depression patients. These effects are noticeable within a relatively short period of time, compared to many of the traditional antidepressants.
Care still should be taken in interpreting that evidence. The methods vary among studies in their treatment protocols, comparison treatment groups, and their lengths of follow-up. Some of the longer-term effects of it are also not so clear as are some of the more successful treatments for depression.
Further research is warranted for NICE to confirm clinical and economic uncertainties concerning esketamine, including longer-term outcomes and course of treatment resistant depression.
So, you see proof of benefit doesn’t mean proof that it helps all people. Furthermore, it provides no evidence that ketamine will cure depression for good.
Side Effects and Monitoring
Side effects of ketamine are a factor in clinical treatment, so it is important that they are assessed, monitored and appropriate treatment is provided. During treatment, some people can experience changes in perception, dizziness, sedation, increased blood pressure, nausea or a feeling of being detached from their surroundings. Esketamine’s product information includes warnings and precautions relating to sedation, dissociation and increases in blood pressure.
Monitoring is important, therefore, as an integral component of treatment. A clinical team can assess and determine if treatment should be continued based on how the person responds to the treatment.
Side effects of misuse of ketamine are also recognised. The 2026 ACMD review of the evidence on harms related to ketamine was decided in favour of its classification as a class B controlled substance in the UK. The hazards of unregulated use must not be taken to be synonymous with well-controlled therapeutic use.
Why Self-Treatment Is Not Equivalent to Clinical Care
Ketamine taken outside of medical supervision is not medical ketamine treatment as it would be received in a specialist clinical service.
Medical treatment includes an assessment prior to prescribe, consideration of other medicines and health conditions, appropriate monitoring and follow-up. There’s also a way for a clinician to see if the treatment is working and if there’s good reason to both discontinue or alter the treatment.
Without this control, the safeguards are removed from the use of ketamine. It can also make it hard to determine whether mood changes are due to the underlying condition, an additional medication, or the substance.
It is critical for someone suffering from depression to go and receive expert evaluation. There may be many causes leading to depression and psychological therapy, antidepressants, physical health assessment or other kinds of support may be required.
Ketamine is a viable option in specialist care for some patients, but shouldn’t be available as a straightforward substitute for acceptable therapy.
References
https://www.nice.org.uk/guidance/ng222
https://www.gov.uk/government/publications/ketamine-an-updated-review-of-use-and-harms
Evidence last checked: 23 September 2026
