What is esketamine (Spravato), and how is it used?

  • Spravato is a prescription medicine, used along with an antidepressant taken by mouth, for treatment-resistant depression (TRD) in adults.
  • Spravato is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if Spravato is safe or effective as an anesthetic medicine.
  • It is not known if Spravato is safe and effective in children. Spravato is not for use in children.

What are the side effects of esketamine (Spravato)?


Spravato can cause serious side effects including:

  • Sedation and dissociation. Spravato may cause sleepiness (sedation), fainting, dizziness, spinning sensation, anxiety, or feeling disconnected from yourself, your thoughts, feelings, space and time (dissociation).
    • Tell your healthcare provider right away if your feel like you cannot stay awake or if you feel like you are going to pass out.
    • Your healthcare provider must monitor you for serious side effects for at least 2 hours after taking Spravato. Your healthcare provider will decide when you are ready to leave the healthcare setting.
  • Abuse and misuse. There is a risk for abuse and physical and psychological dependence with Spravato treatment. Your healthcare provider should check you for signs of abuse and dependence before and during treatment with Spravato.
    • Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.
    • Your healthcare provider can tell you more about the differences between physical and psychological dependence and drug addiction.
  • Spravato Risk Evaluation and Mitigation Strategy (REMS). Because of the risks for sedation, dissociation, and abuse and misuse, Spravato is only available through a restricted program called the Spravato Risk Evaluation and Mitigation Strategy (REMS) Program. Spravato can only be administered at healthcare settings certified in the Spravato REMS Program and to patients enrolled in the program.
  • Increased risk of suicidal thoughts or actions. Spravato may cause worsening of depression and suicidal thoughts and behaviors, especially during the first few months of treatment and when the dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression or a history of suicidal thoughts or actions. How can I watch for and try to prevent suicidal thoughts and actions?
    • Pay close attention to any changes, especially sudden changes, in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions.
    • Tell your healthcare provider right away if you have any new or sudden changes in mood, behavior, thoughts, or feelings.
    • Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Tell your healthcare provider right away if you have any of the following symptoms, especially if they are new, worse, or worry you:
      • attempts to commit suicide
      • worsening depression
      • thoughts about suicide or dying
      • other unusual changes in behavior or mood
  • Increased blood pressure. Spravato can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your healthcare provider will check your blood pressure before taking Spravato and for at least 2 hours after you take Spravato. Tell your healthcare provider right away if you get chest pain, shortness of breath, sudden severe headache, change in vision, or seizures after taking Spravato.
  • Problems with thinking clearly. Tell your healthcare provider if you have problems thinking or remembering.
  • Bladder problems. Tell your healthcare provider if you develop trouble urinating, such as a frequent or urgent need to urinate, pain when urinating, or urinating frequently at night.

The most common side effects of Spravato when used along with an antidepressant taken by mouth include:

If these common side effects occur, they usually happen right after taking Spravato and go away the same day. These are not all the possible side effects of Spravato. Call your doctor for medical advice about side effects.


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What is the dosage for esketamine (Spravato)?

  • You will take Spravato nasal spray yourself, under the supervision of a healthcare provider in a healthcare setting. Your healthcare provider will show you how to use the Spravato nasal spray device
  • Your healthcare provider will tell you how much Spravato you will take and when you will take it.
  • Follow your Spravato treatment schedule exactly as your healthcare provider tells you to.
  • During and after each use of the Spravato nasal spray device, you will be checked by a healthcare provider who will decide when you are ready to leave the healthcare setting.
  • You will need to plan for a caregiver or family member to drive you home after taking Spravato.
  • If you miss a Spravato treatment, your healthcare provider may change your dose and treatment schedule.
  • Some people taking Spravato get nausea and vomiting. You should not eat for at least 2 hours before taking Spravato and not drink liquids at least 30 minutes before taking Spravato.
  • If you take a nasal corticosteroid or nasal decongestant medicine take these medicines at least 1 hour before taking Spravato.
  • Administer Spravato intranasally under the supervision of a healthcare provider.
  • Assess blood pressure prior to and after administration.
  • Evidence of therapeutic benefit should be evaluated at the end of the induction phase to determine need for continued treatment.
  • Nasal Spray: 28 mg of esketamine per device. Each nasal spray device delivers two sprays containing a total of 28 mg of esketamine.

What drugs interact with esketamine (Spravato)?

  • Central Nervous System Depressants: Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation. Closely monitor for sedation with concomitant use of Spravato with CNS depressants.
  • Psychostimulants: Concomitant use with psychostimulants (e.g., amphetamines, methylphenidate, modafanil, armodafinil) may increase blood pressure. Closely monitor blood pressure with concomitant use of Spravato with psychostimulants.
  • Monoamine Oxidase Inhibitors (MAOIs): Concomitant use with monoamine oxidase inhibitors (MAOIs) may increase blood pressure [see Warnings and Precautions (5.6)]. Closely monitor blood pressure with concomitant use of Spravato with MAOIs.


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Is esketamine (Spravato) safe to use while pregnant or breastfeeding?

  • Spravato is not recommended during pregnancy. Spravato may cause fetal harm when administered to pregnant women. If a woman becomes pregnant while being treated with Spravato, treatment with esketamine should be discontinued and the patient should be counseled about the potential risk to the fetus.
  • Esketamine is present in human milk. Because of the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment with Spravato.

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Spravato is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist indicated, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults. Side effects include sedation and dissociation, abuse and misuse, suicidal thoughts or actions, increased blood pressure, problems with thinking clearly, and bladder problems.

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Medically Reviewed on 6/12/2019

All content is from the U.S. Food and Drug Administration (FDA) prescribing information.