Esketamine is a medicine which comes in a nasal spray to be dispensed as an aerosol and is indicated for the treatment of resistant depression and as a general anesthetic. It is a relatively new and promising drug in the field of major depressive disorders that do not respond to conventional antidepressant treatment.
In this article we explain what esketamine is, what its medical uses are and its mechanism of action, the main side effects and contraindications to take into account.
Esketamine is a drug used as a general anesthetic and as a pharmacological therapy to address depression resistant to treatment. It was developed in 1997 by the Johnson & Johnson laboratory, initially as a fast-acting antidepressant medication.
In 2017, this drug was approved for the treatment of adults with depressive symptoms refractory to conventional pharmacotherapy and with a high risk of suicide, a profile of subjects who cannot wait the time it takes for classic antidepressant medications to take effect.
Esketamine is a chemical variation (the S-enantiomer) of a popular substance for medical and recreational use: ketamine This drug is used as a general anesthetic in hospital settings and its possible antidepressant effect has been investigated, although it is also used for recreational purposes in subanesthetic doses, promoting hallucinatory effects and near-death experiences, in which the individual experiences out-of-body sensations and states. mystics.
However, esketamine is presented in the form of a nasal spray for administration as an aerosol, a form that also serves to prevent possible abusive uses of the substance, although it is not yet available in Spanish pharmacies.
Esketamine is used as a general anesthetic, as is its chemical variant, ketamine, with which it shares therapeutic indications. Induction of anesthesia is performed in high-risk patients such as those in anaphylactic shock, in septic shock, with severe bronchospasm, severe liver failure, cardiac tamponade and constrictive pericarditis.
Its anesthetic potential is also used for other types of conditions, such as in the treatment of burns and in situations where it is needed as a supplement to local anesthesia with incomplete nerve blocks.
Another common use of esketamine is as a fast-acting antidepressant, specifically for treatment-resistant depression. This clinical picture describes people who suffer from major depressive disorder who do not respond adequately, and over time, to conventional antidepressant medication.
The nasal spray presentation has the advantage of being a non-invasive technique (unlike intravenous injection) and more convenient for the profile of the subjects treated with the drug. However, in the studies carried out it has been found that patients, after having administered the drug nasally, had to remain sitting for 2 hours, in order to avoid side effects associated with the use of esketamine.
Clinical studies with intranasal esketamine have shown rapid and substantial efficacy. In the study carried out in 2018 by Canuso et. al, esketamine administered intranasally twice a week, in combination with oral antidepressants, reduced suicidal ideation and depression at 4 and 24 hours, although at the end of treatment, after 4 weeks, its effect was not superior to intranasal placebo administered with antidepressant treatment.
Mechanism of action
Esketamine is approximately twice as potent as an anesthetic than the racemic mixture of ketamine and has a three to four times greater affinity for NMDA receptors These types of receptors play an important role in cognitive processes such as learning, neuronal plasticity or memory.
Basically, the mechanism of action of esketamine is to act as a non-competitive antagonist of the NMDA receptor, facilitating the modulation of glutamate receptors and AMPA receptors The activation of these receptors increases the signaling of neurotrophic factors (proteins that promote the survival of groups of neurons) that favor antidepressant effects in the short and long term.
The modulation of glutamate receptors (and the restoration of synaptic connections between neuronal groups) is one of the distinctive characteristics of this drug, since most classic antidepressants do not act on this system and do act on other systems such as the dopaminergic or the serotonergic.
Esketamine too acts, in a way, as an inhibitor of dopamine reuptake, but unlike what happens with ketamine, it does not interact with sigma receptors. On the other hand, this drug tends to increase glucose metabolism in the frontal cortex; This may be due to the dissociative or hallucinogenic effect that esketamine can have in a certain dose range.
Side effects
The vast majority of studies conducted with esketamine have confirmed the safety and effectiveness of the drug. However, like all medications, It is not free of possible side effects after administration Among the most common, it is worth highlighting the following:
Contraindications
Before using esketamine nasal spray aerosol, contraindications must be considered that the consumption of this drug has and consult with the health professional in charge of your medical follow-up. Below are some of the precautions to keep in mind:
