Pronunciation: sprah vah toe
Generic name: esketamine [ es-KET-a-meen ]
Dosage form: Nasal spray
Drug class: Miscellaneous antidepressants

Medically reviewed by Melisa Puckey, BPharm. Last updated on Mar 9, 2025.

What is Spravato?

Spravato (esketamine) is a prescription nasal spray used for treatment-resistant depression (TRD) and major depressive disorder (MDD) with acute suicidal ideation or behavior, in adults. It works by targeting the NMDA receptor, which differs from traditional antidepressants that primarily act on serotonin, norepinephrine, or dopamine pathways.

Spravato's FDA approval was granted to Janssen Pharmaceuticals, Inc., for:

• Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant. 
• Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.

Spravato treatment is used only in a healthcare setting. You will not be able to use this medicine at home.

How Spravato Works

Spravato is an NMDA receptor antagonist.

Spravato mechanism of action (MOA) is by blocking the NMDA receptor (N-methyl-D-aspartate) , which affects glutamate, a key neurotransmitter involved in mood regulation. However, it is not fully understood exactly how Spravato nasal spray exerts its antidepressant effect. This mechanism helps rapidly improve symptoms of depression, often within hours to days, unlike traditional antidepressants that can take weeks.

Spravato REMS

Spravato nasal spray is for use only in adults under a special program called Spravato REMS (Risk Evaluation and Mitigation Strategy). The Spravato REMS program helps to manage the potential risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato nasal spray administration. It can only be administered in a certified healthcare setting under the direct observation of a healthcare provider, and patients must be monitored by a healthcare provider for at least 2 hours. 

The REMS program requires that the healthcare setting, the pharmacy to be certified and the patient to be enrolled in the Spravato REMS program.

Is Spravato a controlled substance?

Yes, Spravato (esketamine) is a Schedule III Controlled Substance in the United States.

Spravato side effects

Common Spravato side effects

Common Spravato side effects may include:

• dissociation, feeling drunk;
• increased blood pressure;
• drowsiness;
• dizziness, spinning sensation 
• feeling anxious;
• nausea, vomiting; or
• decreased sensations (touch or other senses).

Related/similar drugs

Serious Spravato side effects

Get emergency medical help if you have signs of an allergic reaction to Spravato: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Your blood pressure will need to be checked before and after you use Spravato. Esketamine can increase your blood pressure for several hours after each dose. Tell your doctor if you have chest pain, trouble breathing, severe headache, blurred vision, pounding in your neck or ears, or a seizure.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Also, call your doctor at once if you have:

• Extreme drowsiness or feeling like you might pass out;
• Severe dizziness or feelings of floating;
• Unusual changes in mood or behavior;
• Thoughts of hurting yourself;
• Worsening depression;
• Sleep problems;
• Problems with thinking or memory;
• Unusual or unpleasant memories (flashbacks);
• Hallucinations, feeling "spaced out"; or
• Urination problems (painful urination, increased urination, and urgent need to urinate).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Warnings

Spravato treatment can cause severe drowsiness, or feelings of being disconnected from your body or thoughts or surroundings. Spravato nasal spray is used only in a healthcare setting where you can be watched closely for at least 2 hours after each dose.

You will need someone to drive you home after using Spravato treatment.

Some people have thoughts about suicide while taking Spravato nasal spray. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

There is a risk for abuse and dependence with esketamine treatment. Your healthcare provider should check you for signs of abuse and dependence before and during treatment with this medicine. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.

Spravato treatment may cause worsening of depression and suicidal thoughts and behaviors, especially during the first few months of treatment and when the dose is changed. Tell your healthcare provider right away if you have any new or sudden changes in mood, behavior, thoughts, or feelings.

Before taking this medicine

You should not use Spravato nasal spray if you are allergic to esketamine or ketamine, or if you have:

• a blood vessel disorder affecting your brain, chest, stomach, heart, or arms and legs;
• a history of aneurysm;
• a history of bleeding in your brain; or
• an abnormal connection between your veins and arteries (a condition called arteriovenous malformation).

To make sure Spravato treatment is safe for you, tell your doctor if you have:

• heart problems (such as chest pain, heart failure, or a heart valve disorder);
• slow heartbeats that have caused you to faint;
• high blood pressure;
• a heart attack or stroke;
• a brain injury or increased pressure in your brain;
• mental illness or psychosis;
• suicidal thoughts or actions;
• a family history of depression;
• alcoholism or drug addiction; or
• liver disease.

Some people have thoughts about suicide when first using an antidepressant. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Do not use Spravato nasal spray if you are pregnant. Esketamine may harm an unborn baby. Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of esketamine on the baby.

Do not breastfeed while using Spravato.

How should I use Spravato nasal spray?

Spravato is a nasal spray that is used in a healthcare setting. You will give yourself the nasal spray while being supervised by a healthcare professional.

Spravato treatment may cause nausea or vomiting. You should not eat anything for at least 2 hours before receiving your dose. Avoid drinking liquids within 30 minutes before using the medicine.

Read and carefully follow any Instructions for Use that are given to you. Ask your doctor or caregivers if you do not understand these instructions.

You will be watched closely for at least 2 hours after you use Spravato. This medicine can cause side effects such as severe drowsiness, or dissociation (a sense of being detached from your body or emotions, distortions in how you perceive things or people around you).

Your caregivers will decide when you are ready to leave after using this medicine. You will need someone to drive you home. You should not plan to drive yourself anywhere until the next day, after a full night's sleep.

Spravato treatment is usually given 2 times per week at first, and then once every 1 to 2 weeks. Your doctor will tell you how often you need to use the medicine.

Spravato Dosing information

Usual Adult Dose for Depression:

INDUCTION PHASE:
Weeks 1 to 4:
-Day 1: 56 mg intranasally ONCE
-Subsequent doses: 56 to 84 mg intranasally 2 times a week

MAINTENANCE PHASE:
Weeks 5 to 8: 56 to 84 mg intranasally once a week
Week 9 and after: 56 to 84 mg intranasally every 2 weeks OR once a week

Comments:
-IMPORTANT CONSIDERATION: Treatment sessions should be directly supervised by a healthcare provider; treatment sessions should include nasal administration of the dose and post-administration observation.
-Patients who require nasal corticosteroids/decongestants should use the agent(s) at least 1 hour before using this drug.
-Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.
-After the induction phase, evidence of therapeutic benefit should be evaluated to determine the need for continued treatment.
-After Week 8, the dosing frequency should be individualized to the least frequent dosing to maintain remission.

Use: Treatment-resistant depression (TRD) with or without treatment with an oral antidepressant 

Usual Adult Dose for Symptoms in Patients with Major Depressive Disorder with
Acute Suicidal Ideation or Behavior

Use in conjunction with an oral antidepressant.

84 mg intranasally 2 times a week for 4 weeks
-After 4 weeks, the dosage may be decreased to 56 mg intranasally 2 times a week based on tolerability.

-After 4 weeks of treatment, evidence of therapeutic benefit should be evaluated to determine need for continued treatment. 
-LIMITATION OF USE: Efficacy in suicide prevention or in reducing suicidal behavior or ideation has not been demonstrated beyond 4 weeks; this drug does not preclude hospitalization if clinically warranted, even if patients improve after an initial dose of treatment.
-IMPORTANT CONSIDERATION: Treatment sessions should be directly supervised by a healthcare provider; treatment sessions should include nasal administration of the dose and post-administration observation.
-Patients who require nasal corticosteroids/decongestants should use the agent(s) at least 1 hour before using this drug.
-Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.

Use: Treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your Spravato dose.

What happens if I overdose?

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while using Spravato?

Avoid using any other nasal medicines within 1 hour before you use Spravato nasal spray.

Do not drive yourself or do anything that requires you to be awake and alert until the day after your Spravato dose.

What other drugs will affect Spravato?

Tell your doctor about all your other medicines, especially:

• opioid medication;
• a sleeping pill or a muscle relaxer;
• medicine for anxiety, such as diazepam, Valium, Xanax, and others;
• stimulant medicine, including diet pills, or ADHD medication such as Adderall or Ritalin;
• medicine to treat narcolepsy; or
• an MAO inhibitor, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

This list is not complete. Other drugs may interact with esketamine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Ingredients

Active ingredient: esketamine hydrochloride

Inactive ingredients: citric acid monohydrate, edetate disodium, sodium hydroxide, and water for injection 

Company 

Spravato manufacturer Janssen Pharmaceuticals, Inc., Titusville, NJ 08560, USA

Frequently asked questions

• Is Spravato (esketamine) a controlled substance?

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer