Esketamine, An Antidepressant Nasal Spray?
Esketamine is an innovative compound with good prospects in the treatment of depression. And especially in the case of depression resistant to other treatments, since it acts through mechanisms different from known antidepressants.
Esketamine comes from ketamine, a widely used general anesthetic, either intravenously or intramuscularly. It has hypnotic, analgesic and sedative properties. Its action is rapid, in the short term. It is sometimes used as a recreational drug.
Ketamine is a combination of two enantiomers. These are stereoisomeric molecules that are like mirror images of each other. Esketamine is the S enantiomer of ketamine, the most potent and active enantiomer. The other enantiomer is arketamine.
What is esketamine used for?
Recently, esketamine was approved by the United States Drug Administration (FDA) for the treatment of resistant depression as well as another oral antidepressant.
The drug Spravato – marketed by Janssen – is administered by the nasal route. It is indicated for acute depression in adults when other antidepressants do not work.
Several studies also confirm the effectiveness of esketamine in reducing suicidal thoughts. Particularly in depressive patients resistant to conventional treatment and with an immediate risk of suicide.
The main advantages of its use are:
- Faster action – around 4 hours compared to several weeks for other antidepressants –
- Nasal administration, non-invasive
- High bioavailability
Action mechanism
Esketamine is a non-competitive antagonist of the N – methyl D- aspartate receptor (NMDA), a glutamate receptor. In this sense, esketamine acts on the regulation of the levels of this neurotransmitter present in the brain.
Glutamate is an exciting neurotransmitter, which is linked to suicidal behavior, in this case esketamine differs from the traditional mechanisms of antidepressants. In addition, it is believed that esketamine helps restore synaptic connections in neurons. However, the exact mechanism of action of the antidepressant action of esketamine is unknown.
It also acts, to some extent, as a dopamine reuptake inhibitor. It thus increases its activity in the brain. But, unlike esketamine, it does not interact with sigma receptors.
Conditions of use of esketamine
The drug is only available in the United States through a restricted distribution system, due to the risk of side effects. But also for the potential for abuse of this drug. The drug should be sold with its package insert, which includes recommended uses and risks.
Due to the high risk of side effects, this medicine should be administered during a consultation with a doctor, under supervision. It is necessary to monitor the patient for two hours after its administration.
Depending on the laboratory that markets it, the patient and the practitioner must sign a form. The patient must ensure that he has a safe way to return home. This is because he cannot drive for a day after taking the treatment.
Side effects
Intranasal esketamine can cause serious side effects, such as:
- Sedation
- Dissociation
- Dizziness
- Anxiety
- Nausea and vomiting
- Decreased sensitivity
- Increased blood pressure
- Feeling drunk
- Onset of suicidal thoughts
Usually these side effects appear soon after taking and often go away during the day. But it is very important to have them in mind and to control them.
On the day of taking the treatment, you cannot drive or perform activities that require vigilance. One must follow exactly the instructions prescribed by the doctor.
In conclusion, intranasal esketamine is a new and promising, fast-acting option for acute depression. It opens a very interesting perspective and a new approach in the search for depression that we did not know until now.
However, it is not yet authorized in Europe, although its approval has been sought from the European Medicines Agency (EMA). For now, we have to wait and see how longer-term research evolves.
Our thoughts What meaning does this world have? These type of questions are the ones that lead to what is known as existential depression.
