Esketamine, the potentials and limitations



Written by Dr Bassam Dheyaa, Specialist Psychiatrist at The Valens Clinic, Dubai.

When we think about the latest antidepressants in the field, Esketamine would be one the first treatments to come into our minds, the S-enantiomer of ketamine that gained FDA approval in 2019 as a nasal spray for treatment of treatment resistant depression and as an emergency use with faster effect compared to other antidepressant as the mechanism behind its antidepressant effects differs from traditional medications.

Rather than primarily targeting serotonin, norepinephrine, or dopamine receptors, esketamine acts on the glutamatergic system, specifically the N-methyl-D-aspartate (NMDA) receptor.

By modulating glutamate levels, it promotes synaptic plasticity and neural connectivity.


But what does all that mean?

Simply it works on areas that are not target by other antidepressants.

Then why isn’t it one of the first line medications and only approved for severe treatment resistant depression?

From a psychiatrist’s point of view, many cases can be treated with the correct course of traditional antidepressants without the need to advance their therapeutic plan.

From my experience as a psychiatrist in Dubai and patients feedback, two effects were noted, a direct calming effect with a rise in the mood that differs in magnitude and period among patients and that fits with emergency use approved by FDA and a second effect that builds up with it as a treatment plan with regular administrations.

What are the limitations then?

First limitation, is the misconception about it and worry about misuse, as Esketamine is derived from Ketamine that has a long history of primary usage as an anaesthetic and some recreational use, that would make many patients and even professionals worry about prescribing it.

But, we have to keep in mind that it is an enantiomer so it has some of the properties of the original ketamine but not all.


Plus, Esketamine therapy typically involves a controlled regimen supervised by healthcare professionals and patients receive the nasal spray in a clinical setting, initially undergoing a series of treatments over several weeks, with close monitoring to ensure safety and efficacy throughout the treatment process. And even though that for some that can be the second limitation.

Third limitation, would be the right patient profile and indications. As any medicine, if its not prescribed for the right patient then it will not be as effective as expected, and many patients with treatment resistant depression would have co-morbid disorders, traits, and/or medical conditions that can affect the treatment plan or not fitting with medicine effects or side effects.

And it is generally safe when used in the right way and that was shown in a meta analysis published on pub medicine on the 21st of June, 2022, Intranasal Esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.


It is a novel treatment that opens new potentials and benefits but need the right psychiatric assessment and education with continuous follow up.