Ketamine: An Antidepressant Nasal Spray?

Sketamine is an innovative compound with good prospects in the treatment of depression, especially in depressions resistant to other treatments, as it works through different mechanisms than known antidepressants.

Ketamine comes from ketamine (or ketamine), a general anesthetic widely used intravenously or intramuscularly. It has hypnotic, analgesic and amnestic properties. Its action is quick, short-term and is sometimes also used as a recreational drug.

Ketamine is a combination of two enantiomers. These are specular molecules that are mirror images of each other. Ketamine is the S-enantiomer of ketamine, the strongest and most active enantiomer. The other enantiomer is arketamine.

What is ketamine used for?

Recently, ketamine was approved by the FDA for the treatment of resistant depression, along with another oral antidepressant.

The Spravato drug – marketed by Janssen – is for intranasal administration. It is indicated for acute depression in adults, when other types of antidepressants used have not worked.

Several studies also confirm the efficacy of sketamine in reducing suicidal ideation, especially in those depressed patients resistant to conventional treatment and at risk of immediate suicide.

The main advantages of its use are:

• Fast onset of action – about 4 hours compared to several weeks for other antidepressants.
• Non-invasive intranasal administration.
• High bioavailability.

Mechanism of action

Sketamine is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor. In this sense, sketamine acts in the regulation of brain levels of this neurotransmitter.

Glutamate is a stimulating neurotransmitter that is linked to suicidal behavior. In this case, ketamine differs from traditional antidepressant mechanisms. On the other hand, ketamine is believed to help restore the synaptic connections of neurons. However, the exact mechanism by which it exerts its antidepressant action is still unknown.

It also acts, to some degree, as a dopamine reuptake inhibitor. Due to this, its activity in the brain increases. However, unlike ketamine, it does not interact with sigma receptors.

Terms of use

Currently, the drug is only available in the United States through a restricted distribution system, due to the risk of side effects and also the potential for abuse that this drug can have. The prescription for the drug must be accompanied by a package insert, specifying the uses and risks.

Due to the high risk of side effects, this medication must be administered in a doctor’s office, under supervision. Patient monitoring for two hours after administration is required.

According to the laboratory that sells it, the patient and the doctor must sign a form. The patient must ensure that they have a safe way to return home as they cannot drive during the day they receive treatment.

Side effects of ketamine

Intranasal ketamine can cause serious side effects, such as:

• Sedation.
• Dissociation.
• Dizziness.
• Anxiety.
• Nausea and vomiting.
• Decreased sensitivity.
• Increased blood pressure.
• Feeling drunk.
• Appearance of suicidal thoughts.

These side effects usually appear quickly after administration and disappear over the course of the day. However, it is very important to take them into account and control them.

On the day of treatment, the person cannot drive or do any activity that requires attention. The instructions provided by the physician must be strictly followed.

In conclusion, intranasal ketamine is a promising new fast-acting option for severe depression. It opens up a very interesting new window and a new approach to depression research that, until now, was unknown.

In Brazil, it will be available in the second half of 2021. For now, we must wait and see how it works and how research about it evolves in the long term.