La ketamine It is not new to science, but its role in the fight against trough is a relatively recent discovery. While traditional antidepressants act on serotonin and dopamine, ketamine intervenes on glutamate, the most abundant neurotransmitter in the brain. This unique mechanism makes it effective even in the most resistant cases, where other therapies fail.
A spray, just approved in the USA after 31 clinical trials, is the first non-oral option for major depression. But all that glitters is not gold: Its side effects, such as dissociation and drowsiness, require caution. However, for many patients, it may be the only way out of the darkness.
Ketamine: From Anesthetic to Life-Saving Therapy
For decades, ketamine has been an essential tool in hospitals as an anesthetic. Today, its derivative esketamine (twice as powerful) is at the center of a small revolution in psychiatry. Approved by the FDA as Well done, this nasal spray is the only stand-alone therapy for treatment-resistant depression, a condition that affects one-third of patients with major depression.
“Ketamine works on completely different brain mechanisms than traditional antidepressants,” he explains. Gregory Mattingly, a psychiatrist involved in clinical trials. “For many, it’s like turning on a light in a dark room.”
The drug is intended for those who have not benefited after at least two oral antidepressants, or for those who live with thoughts of self-harm. The results? In some cases, the symptoms improve after 24 hours.
The numbers that give hope
The data of the phase 4 trial on Spravato they speak clearly: after four weeks of treatment, the 22,5% of patients achieved remission against the 7,6% of the placebo group. Numbers that confirm years of research, including studies on over 100.000 patients in 77 countries.
placebo and an oral antidepressant. (
© Janssen Pharmaceuticals, Inc, 2025 ).
But how exactly does it work? Ketamine, as mentioned, modulates the glutamate: a neurotransmitter crucial to brain plasticity. Some studies suggest it may even stimulate the formation of new neural connections, counteracting the shrinking of brain areas associated with depression.
“It's like repairing a damaged electrical grid,” he explains. Bill Martin, neuroscientist. “The brain regains flexibility.”
Ketamine and Society: Between Stigma and Curiosity
The FDA approval comes at a time when the ketamine is in the spotlight not only for science, but also for the news. The billionaire Elon Musk, for example, has publicly admitted to using it to manage what he calls “negative brain chemistry.” A statement that has sparked debate about the therapeutic (and non-therapeutic) use of this substance.
Musk isn’t alone: More and more private clinics are offering ketamine-based therapies, often without rigorous supervision. A phenomenon that worries experts, given the risks of abuse and side effects.
Side Effects: The Downside
Spravato, as I pointed out at the beginning, is not free from contraindications. After taking it, the 40% of patients reports feelings of detachment from reality, dizziness or drowsinessSymptoms that usually disappear within two hours, but require clinical monitoring.
“Ketamine is powerful, which is why it should be used with caution,” he warns. Laura Lara Castor, a mental health expert. “But for those who have no alternatives, it’s a godsend.”
The Future of Mental Health
La ketamine paves the way for a new generation of therapies, including psychedelics such as MDMA e psilocybin, currently in testing. The challenge now is to balance innovation and safety, preventing enthusiasm from overtaking science: because, as the case of Musk demonstrates, the boundary between therapy and trend can be blurry.
However, for those struggling with the darkness of resistant depression, this nasal spray could be a beacon. And its light is finally coming on.