Release date 2024.9.2
Characteristics
Esketamine（SPRAVATO®）, which was approved in the U.S. in March 2019 as a treatment for treatment-resistant depression.
Esketamine is an enantiomer of ketamine that exerts antidepressant effects within 24 hours.
In some cases, effects can be observed as early as 4 hours 1), 2), (Figure 1).
（Fig 1）Therapeutic Effects of Esketamine for Treatment-Resistant Depression
Similarly, improvement in suicidal ideation can be seen within 24 hours, sometimes as quickly as 4 hours 2), (Figure 2).
（Fig 2）Improvement of Suicidal Ideation with Esketamine
While ketamine is administered intravenously, Esketamine is administered via nasal spray (Figure 3).
（Fig 3）Shape of SPRAVATO®（esketamine）nasal spray
Esketamine is the S-enantiomer of ketamine and is labeled as (S)-Ketamine (Figure 4).
（Fig 4）Chemical Structure of Ketamine and Esketamine
Mechanism of Action
Esketamine selectively inhibits NMDA glutamate receptors 3).
As a result, it suppresses the GABAergic transmission system and enhances the excitatory glutamate system.
This leads to the release of glutamate, which, through AMPA receptors, increases BDNF production and promotes neurogenesis, resulting in antidepressant effects 4), (Figure 5).
（Fig 5）Mechanism of Action of Esketamine
The NMDA receptor inhibitory action of Esketamine is reported to be relatively stronger compared to other NMDA receptor inhibitors 5), 6), (Figure 6).
（Fig 6）The potency of NMDA receptor inhibiton of Esketamine
Indications
In the U.S., Esketamine has been approved for the following indications:
- Treatment-resistant depression (TRD) in adults
- Depressive symptoms in major depressive disorder with suicidal ideation or behavior in Adults
Dosage and Administration
Esketamine is administered by spraying twice into each nostril (Figure 7).
（Fig 7）Usage of Esketamine
Side Effects
The main side effects observed in clinical trials were as follows (Figure 8):
- Dissociation
- Dizziness
- Nausea
- Sedation
- Vertigo
- Headache
- Dysgeusia (taste disorder)
- Hypoesthesia (reduced sensation)
- Anxiety
- Apathy
- Increased blood pressure
（Fig 8）Main side effects of Esketamine
References
- 1） Popova V et al.: Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry, 176: 428-438, 2019.
- 2） Ionescu DF, et al.: Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). Int J Neuropsychopharmacol, 24: 22-31, 2021.
- 3） Kaur U, et al.: Esketamine: a glimmer of hope in treatment-resistant depression. Eur Arch Psychiatry Clin Neurosci, 271: 417-429, 2021.
- 4） Ahmed et al.: Management of treatment-resistant depression with esketamine nasal spray: clinical questions for daily practice in Gulf Cooperation Council countries. 7:99, 2023.
- 5） Hashimoto K.: Ketamine's antidepressant action: beyond NMDA receptor inhibition. Expert Opin Ther Targets, 20: 1389-1392, 2016.
- 6） Egunlusi AO, et al.: 4-Oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC Blockers with Neuroprotective Potential. Molecules, 25: 4552, 2020.
Column list
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- Characteristics, Mechanism of Action, and Side Effects of Esketamine
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