Is Esketamine Treatment Available in the UK?

Esketamine nasal spray is technically available in the UK, but getting it is far more complicated than that simple “yes” suggests. The drug holds a marketing authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA), meaning it is legally licensed for use. However, the National Institute for Health and Care Excellence (NICE) has not recommended it for routine NHS prescribing, which creates an unusual gap where a licensed medicine sits largely out of reach for most patients who might benefit from it.

The Regulatory Gap Between Licensing and NHS Access

Understanding why esketamine exists in this limbo requires knowing that the UK has a two-step process for new medicines. First, the MHRA assesses whether a drug is safe and effective enough to be sold in the country. Esketamine cleared that bar following the European Medicines Agency’s marketing authorization in December 2019. Second, NICE evaluates whether the drug offers enough value for money to justify NHS spending. In 2022, NICE evaluated esketamine nasal spray for treatment-resistant depression and concluded that there was insufficient cost-effectiveness and long-term safety evidence to support NHS prescribing.¹

Scotland operates under a slightly different system. The Scottish Medicines Consortium accepted esketamine nasal spray for use within NHS Scotland in September 2020, in line with its licensed indication for treatment-resistant depression.² This means that, at least in principle, patients in Scotland have a pathway to esketamine through their NHS services that does not exist for patients in England, Wales, or Northern Ireland.

The result is that across most of the UK, esketamine is primarily accessible through private healthcare providers. A number of specialist clinics have begun offering the treatment, with psychiatrists drawing on early clinical experiences to develop their own best practices. An advisory panel of UK psychiatrists convened in late 2020 specifically to share their clinical experiences using esketamine nasal spray and develop practical guidance, partly because no formal clinical guidelines existed for its use in depression at the time.²

What Esketamine Actually Is

Ketamine, the anaesthetic that has been around since the 1960s, is a racemic mixture, meaning it contains two mirror-image forms of the same molecule. Esketamine is the S-enantiomer, the “left-handed” version, and it has a higher affinity for the NMDA receptor in the brain than its mirror-image counterpart.³ The nasal spray formulation, marketed under the brand name Spravato by Janssen (a Johnson & Johnson subsidiary), was specifically developed to be delivered in a controlled clinical setting rather than at home.

At the receptor level, esketamine blocks a specific type of signaling in the brain. Research suggests that the drug’s rapid antidepressant effects come from selectively dampening certain background currents mediated by NMDA receptors, which in turn triggers a cascade of changes in how brain cells communicate and adapt.⁴ This is fundamentally different from how traditional antidepressants work, which is part of what makes esketamine appealing for people whose depression has not responded to other treatments.

The Evidence Behind the Drug

Esketamine earned its regulatory approvals on the basis of several randomized trials. In a dose-finding study, all three esketamine dose groups showed significantly greater improvement in depression scores compared with placebo after just one week, and the response appeared to build with repeated dosing. Improvement in depression ratings persisted over an eight-week follow-up period even after esketamine doses were stopped.⁵

A separate trial found that flexibly dosed esketamine combined with a newly started oral antidepressant produced significantly greater improvement in depression scores than the oral antidepressant alone at four weeks, and clinically meaningful improvement appeared at earlier time points as well.⁶

Perhaps the most compelling data for long-term use came from a relapse-prevention trial. Among patients who had achieved a stable remission on esketamine plus an antidepressant, continuing esketamine cut the risk of relapse by about half compared to switching to placebo. For those who had achieved a stable response without full remission, the risk reduction was even more dramatic, around 70%.⁷ These findings suggest that esketamine is not just a short-term fix but can help maintain improvement when used on an ongoing basis.

Speed of Effect and Suicidal Ideation

One of esketamine’s most distinctive features is how quickly it works. Traditional antidepressants typically take weeks to produce a noticeable benefit. Esketamine can produce measurable improvement in depression scores within hours of the first dose. A meta-analysis pooling data from multiple trials found that esketamine significantly outperformed placebo on depression scores starting two to four hours after the first administration, and this advantage was maintained through to the end of double-blind treatment periods lasting 28 days.⁸

This rapid onset has particular relevance for people experiencing suicidal thoughts, where waiting weeks for a medication to work is not acceptable. In a study of depressed patients assessed as being at imminent risk of suicide, esketamine showed significantly greater improvement in depression scores at four hours and at 24 hours compared with placebo, with a notable effect on suicidal thoughts at the four-hour mark.⁹

The picture with suicidal ideation is more nuanced than headlines sometimes suggest, though. While the same meta-analysis found that resolution of suicidal ideation was significantly greater for esketamine than placebo at two to four hours, the two groups no longer differed at 24 hours or at 28 days.⁸ Similarly, one key trial found that while depression scores improved significantly with esketamine, other measures of suicidal ideation and clinician-judged suicide risk did not show significant differences between esketamine and placebo groups.¹⁰ The rapid reduction in overall depressive symptoms is well-established, but whether esketamine specifically targets suicidal thinking beyond its general antidepressant effect remains an open question.

Safety, Side Effects, and the Monitoring Requirement

Esketamine is not a take-home medication. Every dose is administered under medical supervision, and patients are monitored for at least two hours afterward. This is because the drug can cause dissociation (feeling detached from your surroundings or your body), dizziness, nausea, sedation, and increases in blood pressure. These effects are typically transient, peaking within the first hour and resolving before the monitoring period ends. But they are common enough that driving and operating machinery are restricted for the rest of the day after each treatment session.

This supervised-administration model is one reason the treatment is expensive and logistically demanding. Each session involves clinic time, nursing staff, and monitoring equipment. For UK patients accessing it privately, the cost of the drug itself is compounded by the cost of the clinical infrastructure around each dose.

Longer-term safety questions have centered on a few areas. Chronic recreational ketamine use is well known to cause serious bladder damage, which naturally raises concerns about medical use. Evidence to date suggests that esketamine at prescribed doses can lead to an increased risk of lower urinary tract symptoms such as painful urination or urgency, but severe bladder damage has not been reported among patients receiving doses in line with prescribing guidelines for depression.¹¹ The difference in dose and frequency between medical use and recreational abuse is substantial, but this remains an area clinicians watch carefully, especially for patients on long-term maintenance treatment.

Abuse potential is another consideration. Esketamine is a controlled substance, and the supervised-administration model exists partly to mitigate the risk of diversion or misuse. The requirement that every dose be administered in a certified healthcare setting, with the patient never taking the nasal spray device home, is a deliberate safeguard.

What Getting Treatment Looks Like in Practice

If you are in England, Wales, or Northern Ireland and want to try esketamine, the realistic pathway right now is through a private psychiatrist or a specialist clinic that offers Spravato treatment. You would typically need a documented history of treatment-resistant depression, meaning you have tried and failed to respond to at least two different antidepressants at adequate doses and durations. The initial phase of treatment usually involves twice-weekly sessions for about four weeks, before potentially reducing to weekly and then fortnightly sessions if you respond well.

Costs vary between clinics and are not trivial. Each session involves the drug itself, the clinician’s time, and the post-dose monitoring period. Some private health insurance policies cover esketamine, but many do not, and it is worth checking before starting treatment. If you are in Scotland, the situation is somewhat more favorable given the Scottish Medicines Consortium’s acceptance, but availability through individual NHS boards can still vary depending on local commissioning decisions and service capacity.

The absence of a NICE recommendation does not mean that NHS clinicians in England are strictly prohibited from prescribing esketamine. Individual NHS trusts can, in theory, fund treatments outside NICE guidance through individual funding requests. In practice, though, these are granted rarely and only in exceptional circumstances, so this is not a reliable route for most patients.

Esketamine Versus Racemic Ketamine

This is where things get interesting for UK patients. While esketamine nasal spray is the branded, regulated product, some UK clinics have for years been offering intravenous racemic ketamine (the mixture of both mirror-image forms) as an off-label treatment for depression. Racemic ketamine infusions are typically less expensive per session than Spravato, and some clinicians have extensive experience with them.

A systematic review and meta-analysis comparing the two found no significant difference in either response or remission rates. Pooled data from six studies gave a nonsignificant trend favoring intravenous ketamine for response, and data from seven studies showed a similar nonsignificant trend for remission.¹² Some evidence suggested a faster onset with intravenous ketamine, though this was inconsistent across studies.

From a practical standpoint, this means the two treatments appear roughly comparable in effectiveness, but they differ in regulatory status and cost structure. Esketamine nasal spray is the only form with a specific license for depression, meaning it comes with standardized dosing protocols, formal safety monitoring guidelines, and regulatory oversight specific to its use in mental health. Racemic ketamine infusions, while widely used off-label, lack that framework. Whether the regulatory structure of esketamine justifies its higher price point compared to generic ketamine infusions is a debate that continues among UK psychiatrists.

Why NICE Said No and Whether That Could Change

NICE’s reluctance was driven by concerns about cost-effectiveness and long-term safety data rather than doubts about whether esketamine works at all. The evidence that esketamine improves depression scores in the short term was not the sticking point. The questions were whether the improvement justifies the ongoing cost of a supervised treatment requiring clinic visits every one to four weeks, and whether enough long-term data exists to understand the full safety profile over years of use.

This is not an unusual outcome for expensive new treatments in the UK. NICE has a well-known threshold for cost per quality-adjusted life year (QALY), and treatments for chronic conditions that require indefinite supervised administration are among the hardest to get across that threshold. The manufacturer can resubmit with updated data or a revised pricing proposal, and there is always the possibility that a technology appraisal could be reconsidered as more real-world evidence accumulates. The advisory panel of UK psychiatrists that published their early clinical experiences explicitly noted the absence of clinical practical guidelines recommending esketamine’s use in depression, framing their own consensus recommendations as a way to fill that gap until formal guidance catches up.²

Other countries have moved faster. The US FDA approved esketamine in March 2019, and Health Canada followed in May 2020.² In those markets, insurance coverage varies but the treatment is more routinely available. The UK’s position of licensing but not recommending is somewhat distinctive and reflects the specific way the NHS balances clinical evidence against economic constraints.

Other Options for Treatment-Resistant Depression in the UK

If you are dealing with treatment-resistant depression and esketamine is not accessible or affordable, it is worth knowing the broader landscape. Augmentation strategies, where a second medication is added to a partially effective antidepressant, remain the most common NHS approach. Lithium augmentation, atypical antipsychotic augmentation, and switching antidepressant classes are all established pathways with NICE backing.

Electroconvulsive therapy (ECT) remains available through the NHS and is sometimes recommended for severe, treatment-resistant cases, particularly where there is a high risk of suicide or where rapid improvement is needed. Repetitive transcranial magnetic stimulation (rTMS) is also offered by some NHS trusts, though availability is patchy. A systematic review looking at treatments for treatment-resistant depression noted that both pharmacological and non-pharmacological interventions showed benefit, though the evidence base for each varies in strength.¹

Psilocybin-assisted therapy has generated considerable excitement as a potential treatment for resistant depression, with UK research institutions playing a leading role in clinical trials. However, psilocybin is not yet licensed for clinical use and remains available only through research protocols. Its regulatory trajectory in the UK remains uncertain.

For patients considering the private route for esketamine specifically, it is worth having a candid conversation with your psychiatrist about what the evidence actually shows for your situation, what the realistic costs will be over a full course of treatment, and whether racemic ketamine infusions might offer a comparable benefit at a lower price. The science is strong enough that esketamine is a legitimate option for the right patient. The question in the UK has never really been whether it works, but whether the system is set up to deliver it affordably and equitably.