Esketamine: What Is Actually New About Treatment-Resistant Depression
Author: The Narcis editorial team · updated: August 2026
🩺 Medical review: awaiting confirmation by a medical reviewer · psychiatrist
Prepared by the Narcis editorial team. The author is a practising psychotherapist, not a physician. This is a review of official prescribing information and clinical guidelines, not a medical opinion: every source below is open and every claim can be checked.
This article explains how a medicine works and what research says about it. Dosing schedules are deliberately omitted. Only a doctor — a psychiatrist or GP — prescribes, changes or stops medication. Narcis is a psychotherapy platform and does not prescribe. Never start or stop a medicine based on an article: for some drugs, abrupt discontinuation is more dangerous than continuing. Approved indications for the same drug differ between countries.
Do not wait for the medicine to “kick in” if you notice:
a sharp worsening of your state · thoughts of self-harm · unusual agitation or signs of mania or hypomania · seizures · confusion · a severe allergic reaction. Seek medical help immediately. Where to turn →
The word “ketamine” tends to trigger either excitement — “depression can disappear in hours” — or fear because of associations with anesthesia and recreational use. Esketamine sits between these extremes: it is a real medical treatment with a different mechanism, but it is not a take-home spray for a bad day.
What changes the picture
Esketamine is the S-enantiomer of ketamine and an NMDA-receptor antagonist. In the EU, intranasal esketamine is approved in combination with an SSRI or SNRI for adults with treatment-resistant major depression after failure of at least two different antidepressant treatments in the current episode.
A defining feature is administration under direct medical supervision. Acute effects can include elevated blood pressure, sedation, dissociation, and other symptoms. This is not a medication patients simply take home for occasional use.
EMA describes a trial in which adding esketamine to an antidepressant improved MADRS scores by about 3.5 points more over four weeks than nasal placebo plus an antidepressant. A 2025 systematic review and meta-analysis also found a small but statistically significant overall benefit, while noting that some individual randomized trials were negative.
In real life, treatment looks more like a specialized program: confirm treatment resistance, select concomitant medication, attend clinic sessions, remain under observation after dosing, and continue only if there is meaningful benefit.
Esketamine’s major contribution is a different mechanism for some people who have not responded to several previous strategies. That is an important expansion of options, not a miracle rapid treatment for ordinary anxiety or situational sadness.
A typical situation without labels
A person with treatment-resistant depression reads about esketamine as a “revolutionary nasal spray” and imagines a fast home medication. The real model is far more controlled: specific indications, supervised administration, monitoring, and use within a treatment system rather than as an ordinary substitute for a first antidepressant.
Where the important boundary lies
Medication indications vary across countries and regulators. this topic may be approved or recommended for a condition in one system and used differently in another. An article cannot replace local labeling or a clinician’s decision.
What psychotherapy can change
Psychotherapy can be particularly useful after partial medication response. When this topic reduces symptom intensity, a person may have more capacity to work on what medication does not automatically restructure: avoidance, relationships, self-worth, habits, trauma responses, and life decisions.
What to check in practice
For a prescriber conversation about “this topic,” bring your own data rather than an internet ranking: the target symptom, when it began, what has already been tried, other medicines and medical conditions, and which adverse effects would be especially difficult for you. After starting treatment, track changes in sleep, anxiety, mood, functioning, and side effects over time. Sudden deterioration, suicidal thoughts, marked agitation, signs of mania, an allergic reaction, or another acute symptom require prompt medical contact or emergency care. Do not change the dose or discontinue a prescription medicine on the basis of an article.
Medical note. Important: comparisons in this article are not individualized prescribing advice. Effectiveness and tolerability depend on diagnosis, comorbidities, other medicines, prior response, and individual risks.
Books and sources
• EMA: Spravato (esketamine) — EPAR
• EMA: Spravato public assessment report
• 2025 systematic review/meta-analysis of esketamine in adult depression
If this topic resonated — you do not have to sit with it alone.
Therapy can be part of comprehensive care — find a specialist →Sources checked: August 2026. Guidelines and prescribing information change over time — if this article is old, check the original via the link.
This article is for information only and is not a substitute for an individual consultation with a specialist.