Esketamine: uses and side effects of this drug

Esketamine is a medication which comes as a nasal spray to be dispensed as an aerosol and which 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, its medical uses and its mechanism of action, the main side effects and contraindications to take into account.

• Related article: "Types of psychoactive drugs: uses and side effects"

What is esketamine?

Esketamine is a drug used as a general anesthetic and as a drug 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 for the time it takes for antidepressant medications to take effect classics.

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, leading to hallucinatory effects and near-death experiences, in which the individual experiences extracorporeal sensations and states mystics.

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

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, in septic shock, with severe bronchospasm, severe hepatic 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 nerve blocks incomplete.

Another of the common uses of esketamine is as a fast-acting antidepressant., specifically for treatment-resistant depression. This clinical picture describes people suffering 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 subjects treated with the drug. However, in the studies carried out it has been possible to verify that the patients, after having administered the drug by nasal route, they had to remain seated for 2 hours, in order to avoid side effects associated with the use of the 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 weekly, 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.

• You may be interested in: "Types of antidepressants: characteristics and effects"

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. This type of receptors have 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. Activation of these receptors increases the signaling of neurotrophic factors (proteins that favor the survival of groups of neurons) that favor short- and long-term antidepressant effects term.

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

Esketamine also acts, to a certain extent, as a dopamine reuptake inhibitor, but 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 range of doses.

Side effects

The vast majority of studies conducted with esketamine have confirmed the safety and efficacy of the drug. However, like all medicines, It is not free of possible side effects after its administration.. Among the most common, it is worth highlighting the following:

• Nausea
• dizziness
• Alterations in the sense of taste
• dizziness
• metallic taste
• headache
• Paresthesia (tingling sensation)
• Blurry vision
• Nervousness or anxiety

contraindications

Before using esketamine nasal spray, consider contraindications who is consuming this drug and consult with the health professional in charge of your medical follow-up. Here are some of the precautions to keep in mind:

• Allergy to esketamine, ketamine, or any medications or ingredients that are included in the nasal spray.
• Use of amphetamines, anxiolytics, armodafinil, MAO inhibitors such as phenelzine, procarbazine, tranylcypromine, selegiline, methylphenidate, modafinil, opioid drugs, anti-seizure drugs, sedatives.
• Disease in the blood vessels of the brain, chest, stomach, arms, or legs; arteriovenous malformations or a history of cerebral hemorrhages.
• History of stroke, heart attack, brain injury, or conditions that cause increased pressure in the brain. Heart valve disease, heart failure, high blood pressure, slow or irregular heartbeat, shortness of breath, chest pain, heart or liver disease.
• Being pregnant or breastfeeding.
• If you are going to have surgery, including dental surgery.

Bibliographic references:

• 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). Can a framework for the safe use of ketamine be established? Am J Psychiatry, 175(7).