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Spravato Side Effects

Spravato (esketamine) is a revolutionary medication for treatment-resistant depression and major depressive disorder. This FDA-approved medication has demonstrated promising results in clinical trials for reducing depressive symptoms. It is recommended to use Spravato in tandem with an oral antidepressant for optimal efficacy. In this article, we will discuss the specifics of Spravato, its indications, potential side effects, and more.

How does Spravato work?

Esketamine, also known as Spravato, received FDA approval in 2019 for treatment-resistant depression. This medication offers a rapid delivery system, alleviating depression symptoms within a few hours. Esketamine administration involves spraying the medicine into each nostril, followed by a two-hour monitoring period. The standard dosing regimen typically consists of twice-weekly administration for approximately four weeks, followed by a transition to once-weekly administration for an additional four weeks. [6]

Esketamine belongs to a class of drugs called NMDA receptor antagonists, which block the N-methyl-D-aspartate (NMDA) receptor. Although it isn’t fully understood, esketamine works by targeting a different brain pathway than traditional antidepressants.

Ketamine, the parent drug of esketamine, has a unique mechanism of action that triggers the production of glutamate, a neurotransmitter promoting the brain’s formation of new connections. This characteristic sets it apart from traditional antidepressants, as it enhances the brain’s flexibility and openness to positive changes in thoughts and behaviors.[2]

Esketamine, approved by the FDA for treatment-resistant depression (TRD) and major depressive disorder (MDD), has shown promise beyond its approved uses. Some off-label applications include treating anxiety disorders and Post Traumatic Stress Disorder (PTSD). [3]

Who shouldn’t take Spravato?

Esketamine is not appropriate for everyone. Children and teenagers are not candidates for Spravato. Typically, Spravato is used when adults have tried at least two other antidepressants and have not experienced relief from depression symptoms. [6] There is a chance of abuse. Esketamine’s potential for addiction and misuse leads to its Schedule 3 classification. [6]

Before starting Spravato, tell your healthcare provider about all medications, including over-the-counter products and supplements, as there are significant drug interactions with certain medications. It is also critical to provide a complete physical and mental health history before starting Spravato, especially if individuals have any of the following conditions:

  • Currently have or have ever had a history of psychosis.
  • Allergy to ketamine, esketamine, or other ingredients in Spravato.
  • History of vascular conditions in the brain or other body parts, such as aneurysmal vascular disease or arteriovenous malformation.
  • Cardiovascular, cerebrovascular disease, or heart disease.
  • History of drug abuse
  • Hypertension or stroke
  • Liver disease (moderate to severe
  • History of brain injury, including changes in pressure in the brain or bleeding in the brain
  • If you are pregnant or planning to become pregnant. [8]

While the research shows promising results, weighing the benefits and risks when deciding on any treatment is important.

What are the side effects of Spravato?

Side effects are possible, especially when starting any medication. These side effects may stop once your body adjusts. The following side effects are common but usually do not require medical treatment and may include: 

  • Dissociation (feeling disconnected from oneself, thoughts, or feelings).
  • Sedation (sleepiness)
  • Headache
  • Nausea or vomiting
  • Dizziness or vertigo
  • Increase in blood pressure.
  • Change in taste.
  • Reduced sense of touch or sensation

Less common side effects include:

  • Rapid heart rate
  • Dry mouth
  • Constipation
  • Diarrhea
  • Anxiety
  • Slurred or slow speech
  • Tremors
  • Euphoric mood
  • Frequent urination
  • Nasal or throat irritation or pain
  • Sweating [8]

There is potential for some individuals taking esketamine to experience more severe side effects. If you or someone you know experiences suicidal thoughts or behaviors about harming yourself, you should contact a health provider immediately. Individuals taking esketamine should not suddenly stop taking it, even if they feel better. Missing a dose or stopping esketamine can increase the risk of relapse and depression symptoms. [4]

How effective is Spravato?

Research has shown that esketamine nasal spray (Spravato) effectively reduces symptoms of treatment-resistant depression (TRD) when used alongside a standard antidepressant.

One study revealed that around 70% of patients with treatment-resistant depression experienced improvement with esketamine and an oral antidepressant. At the same time, just over half of the comparison group who received a placebo showed similar benefits. [2]

In a phase III trial, 197 participants with moderate to severe treatment-resistant depression were randomly assigned to receive either esketamine or a placebo twice weekly in addition to their antidepressant. The group receiving esketamine alongside the antidepressant saw a more significant decrease in depression scores than the placebo group after 28 days. Impressively, the improvement was noticeable within 24 hours of the initial esketamine dose. [7]

Another study comparing patients who received esketamine or placebo demonstrated that 53% of those taking esketamine experienced significant symptom improvement. In contrast, only 42% of the placebo group reported similar benefits. [5]


In conclusion, Spravato, as an adjunct treatment for treatment-resistant depression, has shown promising results in multiple studies, providing hope for patients who have not responded adequately to traditional antidepressant therapies. However, it is important to remember that Spravato should only be used in combination with traditional antidepressant therapies. Furthermore, Spravato should only be taken under the supervision of a healthcare provider. Finally, Spravato may not be suitable for everyone and must be used with caution.

Don’t let mental health challenges hold you back from living a fulfilling life. Take the first step towards exploring Spravato by contacting Neuro Wellness Spa today. We are committed to providing you with the highest quality care and support on your journey to improved mental well-being.


  1. Bahr, R., Lopez, A., & Rey, J. A. (2019). Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant. P & T: a peer-reviewed journal for formulary management, 44(6), 340–375.
  2. Chen, J. (2022). How Ketamine Drug Helps with Depression. Yale Medicine.,prompts%20the%20brain%20to%20form%20new%20neural%20connections.
  3. Derakhshanian, S., Zhou, M., Rath, A., Barlow, R., Bertrand, S., DeGraw, C., Lee, C., Hasoon, J., & Kaye, A. D. (2021). Role of Ketamine in the Treatment of Psychiatric Disorders. Health psychology research, 9(1), 25091.
  4. Esketamine (Spravato) National Alliance on Mental Illness.
  5. Jalloh M. (2020). Esketamine (Spravato) for Treatment-Resistant Depression. American family physician, 101(6), 339–340.
  6. LaBruna, H. (2022). Ketamine for treatment-resistant depression: What you need to know. Mayo Clinic.
  7. Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W. C., & Singh, J. B. (2019). 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. The American journal of psychiatry, 176(6), 428–438.
  8. Spravato (esketamine) nasal spray, CIII. (2020).
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