Esketamine: uses and side effects of this drug

Esketamine is a drug sometimes used as an antidepressant.

Esketamine is a medication which comes as a nasal spray to be dispensed as an aerosol and is indicated in the treatment of resistant depression and as a general anesthetic. It is a relatively new and promising drug in the field of severe depressive disorders that do not respond to conventional antidepressant treatment.

In this article we explain what is esketamine, what are its medical uses and its mechanism of action, the main side effects and contraindications to take into account.

What is esketamine?

Esketamine is a drug used as a general anesthetic and as a pharmacological therapy to address treatment-resistant depression. treatment-resistant depression. It was developed in 1997 by the Johnson & Johnson laboratory, initially as a fast-acting antidepressant drug.

In 2017, this drug was approved for the treatment of adults with depressive conditions refractory to conventional pharmacotherapy and with a high risk of suicide, a profile of subjects who cannot wait the time it takes for classical antidepressant drugs 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 has been investigated for its possible antidepressant effect, 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 mystical states.

However, esketamine comes in the form of a nasal spray for administration as an aerosol, a form that also serves to prevent possible abuse of the substance, although it is not yet available in Spanish pharmacies.

Medical uses

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.such as those in anaphylactic shock, septic shock, severe bronchospasm, severe hepatic insufficiency, 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 in 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 individuals suffering from a major depressive disorder that does 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, studies have shown that patients, after nasal administration of the drug, had to remain seated 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 2018 study by Canuso et al. 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 as the racemic mixture of ketamine and has a three to four times greater affinity for NMDA receptors.. These receptors play an important role in cognitive processes such as learning, neuronal plasticity and 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.. Activation of these receptors increases the signaling of neurotrophic factors (proteins that promote the survival of neuronal clusters) that promote short- and long-term antidepressant effects.

The modulation of glutamate receptors (and the restoration of synaptic connections between neuronal clusters) is one of the distinctive features of this drug, since most classical antidepressants do not act on this system and do act on other systems such as the dopaminergic or serotonergic systems.

Esketamine also acts, in a certain way, as a dopamine reuptake inhibitorbut unlike 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 performed with esketamine have confirmed the safety and efficacy of the drug. However, like any drug, it is not without possible side effects, it is not free from possible side effects after administration.. Among the most common are the following:

• Nausea
• Dizziness
• Alterations in the sense of taste
• Dizziness
• Metallic taste
• Headache
• Paresthesia (tingling sensation)
• Blurred vision
• Nervousness or anxiety

Contraindications

Before using esketamine nasal spray, you should consider the contraindications to the use of this drug and consult with your health care professional. and consult with the health professional in charge of your medical follow-up. Some of the precautions to be taken into account are described below:

• Allergy to esketamine, ketamine or any medications or ingredients included in the nasal spray.
• Use of amphetamines, anxiolytics, armodafinil, MAO inhibitors such as phenelzine, procarbazine, tranylcypromine, selegiline, methylphenidate, modafinil, opioid drugs, Anticonvulsant drugs, sedatives.
• Disease in the blood vessels of the brain, chest, stomach, arms or legs; arteriovenous malformations or history of cerebral hemorrhages.
• History of stroke, heart attack, brain injury or conditions causing increased brain pressure. Heart valve disease, heart failure, high blood pressure, slow or irregular heart rhythm, shortness of breath, chest pain, heart or liver disease.
• Being pregnant or breastfeeding.
• Si se va a someter a una cirugía, incluyendo cirugía dental.

Referencias bibliográficas:

• Canuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., ... & Drevets, W. C. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. American journal of psychiatry, 175(7), 620-630.
• Freedman, R., Brown, A. S., Cannon, T. D., Druss, B. G., Earls, F. J., Escobar, J., ... & Mayberg, H. S. (2018). ¿ Puede establecerse un marco para el uso seguro de la ketamina?. Am J Psychiatry, 175(7).