Treatment-resistant depression: how a nasal spray can help in the long term
When depression dominates life and conventional therapies are ineffective, something unexpected can help in some cases: a nasal spray. A new study has now raised hopes that esketamine, a drug used in anaesthesia medicine, can provide rapid relief for treatment-resistant depression.
An agonising lack of motivation, deep depression and the loss of all joy. For people with severe depression, everyday life is an enormous, often unbearable feat of strength. This situation becomes particularly dramatic when there is no relief even after months of medical treatment. And this is not uncommon: Up to 30 per cent of all patients simply do not respond to the usual antidepressants. They suffer from treatment-resistant depression. Those affected often try one medication after another, suffer from side effects and fall further behind psychologically after each failed attempt.
However, medicine now has a new tool in its repertoire for these stubborn cases: esketamine, a specially isolated and highly effective sub-component of the well-known intoxicant and anaesthetic ketamine.
A completely different pathway in the brain
To understand why esketamine works where conventional tablets fail, it helps to take a look at the neurotransmitters in the brain. Traditional antidepressants almost always target the known systems for serotonin or noradrenaline. They are designed to make the mood-enhancing neurotransmitters available between the nerve cells for longer. In the case of treatment-resistant depression, however, this approach leads to a dead end.
Esketamine bypasses this system completely. Instead, the active ingredient influences the so-called glutamate system in the brain and blocks a specific receptor (NMDA) there. This chemically flips a new switch, so to speak. The brain is stimulated to form new neuronal connections in a very short time. Where the chronic disease previously caused connections between nerve cells to atrophy, esketamine can create new networks.
Fast and lasting relief
The fact that this principle works in a strictly controlled laboratory environment is already known to experts. The corresponding nasal spray (Spravato) received EU authorisation at the end of 2019 and has also been used in Germany for psychiatric emergencies and treatment resistance since 2021. In Switzerland, the active ingredient esketamine has also been officially authorised by the Swiss Agency for Therapeutic Products Swissmedic for the treatment of severe depression since the beginning of 2020. To date, however, there has been a lack of reliable long-term data from real-life medical practice.
This is now underpinned by recent analyses presented at the 34th European Psychiatric Congress (EPC) in Prague. For the European observational study initiated by the manufacturer, hundreds of severely depressed people were treated with the nasal spray under real-life conditions and then followed up in the long term.
The data show that the nasal spray alleviated the depressive symptoms and that the effect persisted even after discontinuation. The psychiatrist involved in the study, Dr Christine Reif Leonhard from the University Medical Centre Frankfurt, emphasises the uniqueness of the study because it was the first to show this lasting effect under everyday conditions. Even six months after the end of treatment, mental stability was maintained in the vast majority of those affected.
Why not go straight for the spray
In view of these success figures, the question arises as to why esketamine spray is not prescribed immediately for depressive moods. Why do sufferers have to go through other forms of therapy for months or years in vain? The answer lies in the strong effects and potential side effects of esketamine.
The medication is not a spray for the medicine cabinet at home. It can rapidly raise blood pressure and trigger so-called dissociative states. Patients feel temporarily detached from their own body. It is precisely this mind-altering effect that makes its relative ketamine so well-known as an illegal party drug. As such intense states of intoxication and physical reactions must be controlled, the nasal spray may only be used under medical supervision. Those affected must take the medication in a doctor's surgery or clinic and be monitored by specialist staff for at least two hours afterwards.
Esketamine therefore remains a powerful but very specialised drug in psychiatry. It is only used when the established standard therapies are no longer effective - but can then make all the difference in some cases.
Science editor and biologist. I love animals and am fascinated by plants, their abilities and everything you can do with them. That's why my favourite place is always the outdoors - somewhere in nature, preferably in my wild garden.
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