Finding the Right Dosage for the Esketamine Nasal Spray for Depression

When the FDA approved the fast-acting esketamine nasal spray Spravato™ in early 2019, it gave newfound hope to many people who struggle with treatment-resistant depression (TRD), or any major depressive disorder that hasn’t improved with traditional antidepressants.       

As a fully certified ketamine clinic, TMS & Brain Health is committed to providing innovative and individualized solutions for patients with TRD, including in-office esketamine treatments. 

Let’s explore how Spravato nasal spray works, what the standard treatment protocol is like, and which factors help determine the right dosage for you.  

Esketamine actions

Esketamine is a close cousin of ketamine, a widely used FDA-approved anesthetic that’s also used off-label to treat persistent depression. Given as an intravenous (IV) infusion, ketamine is made up of two mirror-image molecules — arketamine (“R” ketamine) and esketamine (“S'' ketamine).

Spravato, which is given as a nasal spray, only contains esketamine, the more potent of the two molecules. Higher potency means that Spravato is more effective at lower doses and less likely to cause side effects like sedation (drowsiness) and dissociation (fuzzy thinking).   

Esketamine provides swift and sustained symptom relief by binding to the NMDA receptors in your brain, triggering the rapid activation and transmission of glutamate, one of the primary neurotransmitters that determines your mood and steers your behavior.  

Traditional antidepressants take a much slower, more meandering route to stimulate glutamate transmission in your brain. After building up in your system for several weeks, they reawaken mood-boosting neurotransmitters called monoamines (i.e. serotonin). These monoamines are what bind to your NMDA receptors to activate glutamate transmission and improve your mood. 

Esketamine protocol

Spravato is a self-administered treatment that’s done under the supervision and guidance of a qualified physician in an esketamine-certified clinical setting. 

To be eligible for an esketamine prescription, you must have a history of TRD and have tried at least two conventional antidepressants (at the correct dosage and for the recommended length of time) without success. 

Once you’re approved, you start taking a daily oral antidepressant, which you must continue taking for the duration of your treatment plan. Your in-office Spravato sessions occur two times a week for the first month (weeks one through four), and once a week for the second month (weeks five through eight). 

Depending on how well your symptoms respond to the medication in the first two months of treatment, you may continue having one session per week, or you may go back to having two weekly sessions. 

Even though it only takes a moment to spray the medicine into each nostril, you remain under close supervision in the treatment room for about two hours.  

This lengthy observation period serves two purposes: It helps your doctor determine how well you respond to the treatment, and it ensures your safety should you experience any delayed or prolonged side effects.  

Esketamine dosage 

Because of the potential for abuse and the risk of dissociation and sedation, esketamine nasal spray is part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) drug safety program, which is designed to ensure proper use so that that the medication’s benefits outweigh its risks.   

As such, the REMS set of standards for esketamine includes guidelines for determining proper dosage. Spravato is available in two different dosing kits — one that supplies 56 milligrams of esketamine, and one that supplies 84 milligrams of medicine.  

All adults receive a starting dose of 56 milligrams on the first day. Depending on your reaction to the medication, you may continue receiving 56 milligrams of esketamine for the first month, or you may be switched to the higher 84 milligram dose. 

As your treatment continues, your doctor may adjust your dose as needed and tolerated. The overriding goal is to help you achieve optimal symptom response or complete remission safely, or at the lowest possible esketamine dosage.   

To find out how Spravato can help you overcome depression, call 833-867-2329 to speak with one of our qualified esketamine experts today, or click online to schedule a visit to your nearest TMS & Brain Health office in Los Angeles or Santa Monica, California, any time. 




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