Spravato (esketamine) is a prescription drug that’s approved to treat certain forms of depression. Esketamine comes as a nasal (nose) spray that you inhale.

Spravato is approved to treat the following conditions in adults:

Doctors do not always prescribe Spravato. They prescribe it with at least one other antidepressant medication that you take by mouth.

To learn more about Spravato’s uses, see the “What is Spravato used for?” section below.

Spravato basics

Spravato contains the active ingredient esketamine. It belongs to a group of drugs called N-methyl-D-aspartate (NMDA) receptor blockers. Spravato is a brand-name medication. A generic version of the drug isn’t currently available.

Like most drugs, Spravato may cause mild or serious side effects. The lists below describe some of the more common side effects that Spravato may cause. These lists don’t include all possible side effects.

Keep in mind that side effects of a drug can depend on:

  • your age
  • other health conditions you have
  • other medications you take

Your doctor or pharmacist can tell you more about the potential side effects of Spravato. They can also suggest ways to help reduce side effects.

Mild side effects

Here’s a list of some of the mild side effects that Spravato can cause. To learn about other mild side effects, talk with your doctor or pharmacist or read Spravato’s prescribing information.

Mild side effects that people taking Spravato have reported include:

  • nausea and vomiting
  • vertigo or feeling dizzy
  • loss of sensation in part of your body
  • fast heartbeat
  • diarrhea
  • feeling drunk
  • anxiety
  • headache
  • lack of energy and mental alertness
  • insomnia (difficulty sleeping)
  • excessive sweating
  • irritation and discomfort in the nose or throat
  • muscle pains
  • mild allergic reaction*

Mild side effects of many drugs may go away within a few days to a couple of weeks. But if they become bothersome, talk with your doctor or pharmacist.

* To learn more about this side effect, see the “Allergic reaction” section below.

Serious side effects

Serious side effects from Spravato can occur. If you have serious side effects from Spravato, call your doctor right away. But if you think you’re having a medical emergency, you should call 911 or your local emergency number.

Serious side effects that people taking Spravato have reported include:

* For more information, see the “What should be considered before taking Spravato?” section.
† To learn more about this side effect, see the “Allergic reaction” section below.

Allergic reaction

Some people may have an allergic reaction to Spravato.

Symptoms of a mild allergic reaction can include:

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include swelling under your skin, usually in your eyelids, lips, hands, or feet. They can also include swelling of your tongue, mouth, or throat, which can cause difficulty breathing.

Call your doctor right away if you have an allergic reaction to Spravato. But if you think you’re having a medical emergency, call 911 or your local emergency number.

Prices of prescription drugs can vary depending on many factors. These factors include whether you have insurance coverage and which pharmacy you use.

If you have questions about what your cost for Spravato treatment may be, talk with your doctor or pharmacist. A program called Spravato withMe may also help lower the cost of the drug.

You can also check out this article to learn more about saving money on prescriptions.

Your doctor will recommend the dosage of Spravato that’s right for you. Below are commonly used dosages. You’ll receive your Spravato doses under medical supervision. Most likely, you’ll take your doses in your doctor’s office.

For more details about Spravato’s dosage, see this article.

Form and strength

Spravato comes as a solution in a nasal (nose) spray bottle that you’ll inhale. Each nasal spray bottle releases two sprays for a total of 28 milligrams (mg) of esketamine.

Recommended dosages

The recommended dosages of Spravato depend on the condition your doctor prescribes it to treat.

Dosage for treatment-resistant depression

For treatment-resistant depression, your doctor will prescribe a dosing schedule for Spravato. They’ll adjust your dose based on how well the medication is working and any side effects you’re experiencing.

Your dosing schedule will be split into two phases. The first phase is called the induction (starting) phase, and it lasts 4 weeks. For weeks 1 through 4, you’ll receive two doses per week on two separate days.

If your doctor determines that you should continue receiving Spravato treatment after 4 weeks, you’ll begin the maintenance (long term) phase. In weeks 5 through 8 of treatment, you’ll take maintenance doses once per week. For week 9 and beyond, you’ll receive a dose once every 1 or 2 weeks.

Dosage for major depressive disorder with suicidal thoughts or behaviors

For major depressive disorder with suicidal thoughts or behaviors, you’ll take a dose of Spravato twice per week for 4 weeks. Depending on how your body responds to Spravato, your doctor may prescribe a lower dose.

After 4 weeks, your doctor will check if the medication is working for you. They’ll let you know if you should continue treatment with Spravato.

Questions about Spravato’s dosing

Below are some common questions about Spravato’s dosing.

  • What if I miss a dose of Spravato? If you miss an appointment to take a dose of Spravato, call your doctor’s office or the healthcare facility to reschedule your appointment. Your doctor can determine when you should receive your next dose after a missed dose. You may need to take a different dose and follow a different dosing schedule after a missed dose.
  • Will I need to take Spravato long term? Your doctor will tell you if you need long-term treatment with Spravato for treatment-resistant depression. If your side effects aren’t too bothersome and Spravato is working for you, you can take it long term. Talk with your doctor to find out how long you’ll need Spravato treatment.
  • How long does Spravato take to work? In studies of people with treatment-resistant depression receiving Spravato and taking an antidepressant by mouth, their depression symptoms began to ease within 24 hours of taking a dose. For people with major depressive disorder with suicidal thoughts and behaviors, their depression symptoms began to ease after 4 hours. Depression symptoms continued to decrease over the next 4 weeks of treatment in both groups.

Find answers to some commonly asked questions about Spravato.

Does Spravato cause any long-term side effects?

It’s unknown if Spravato causes long-term side effects. In studies, both mild and severe side effects occurred on the day a person inhaled the medication. These side effects typically went away that same day.

What is Spravato’s mechanism of action (how does it work)?

Spravato works by blocking a protein called N-methyl-D-aspartate (NMDA) receptor in the brain. Some studies suggest that the NMDA receptors play a role in depression. But it’s not known exactly how Spravato works to help treat depression.

Is Spravato approved to treat anxiety or bipolar disorder?

No, Spravato isn’t approved by the Food and Drug Administration (FDA) to treat anxiety or bipolar disorder. But in some cases, doctors may prescribe the drug off-label for these uses. (Off-label use is when a drug that’s FDA-approved to treat one condition is used to treat a condition it’s not approved for.)

One study showed that ketamine (a drug very similar to Spravato) helps treat symptoms of anxiety. A report suggests that Spravato might help manage depressive symptoms in people with bipolar disorder.

If you’re interested in receiving Spravato treatment off-label for a condition other than depression, talk with your doctor.

What should I know about Spravato vs. a ketamine infusion?

Spravato contains the active ingredient esketamine, which is very similar to ketamine. (Ketamine is approved for use as general anesthesia during surgery.)

Although most doctors don’t prescribe ketamine to treat depression, a review of studies suggests it may be an effective treatment option for some people.

Spravato and ketamine are given in different ways. Spravato comes as a nasal (nose) spray that you inhale. Ketamine is given through an intravenous (IV) infusion by your doctor or another healthcare professional. (An IV infusion is an injection into a vein over a period of time.) Ketamine may also be given as an intramuscular injection, depending on the situation.

If you have other questions about how Spravato and ketamine compare, talk with your doctor.

Is Spravato a controlled substance?

Yes, Spravato is a controlled substance. It’s classified as a Schedule III drug. This means Spravato has a medical use but also has an increased risk of dependence. (With dependence, your body needs a drug to feel how it usually feels.)

Spravato also has a boxed warning for misuse. (With misuse, a drug is taken in a way other than how it’s prescribed.) To learn more, see the “What should be considered before taking Spravato?” section below.

Spravato is approved to treat depression in adults. Specifically, doctors prescribe Spravato along with another antidepressant for:

See the sections below for details on these uses.

It’s unknown how Spravato works to help treat depression. It blocks a certain protein in the brain called N-methyl-D-aspartate (NMDA) receptors. Some studies suggest that the NMDA receptors play a role in depression.

Spravato for treatment-resistant depression

Spravato is approved for adults with treatment-resistant depression. This is a type of depression that hasn’t improved after you’ve tried at least two other antidepressant drugs.

Spravato for major depressive disorder with suicidal thoughts or behaviors

Spravato is also approved for adults with major depressive disorder with suicidal thoughts and behaviors.

Symptoms of major depressive disorder include:

  • persistent low mood
  • little interest in activities you used to enjoy
  • feelings of guilt or worthlessness
  • fatigue (low energy)
  • difficulty focusing
  • increase or decrease in appetite
  • insomnia (difficulty sleeping)
  • having a hard time completing daily activities
  • suicidal thoughts or behaviors

Limitations of use

Doctors should not prescribe Spravato in certain situations. Doctors don’t prescribe Spravato to prevent suicide or to reduce suicidal thoughts and behaviors. In studies, the drug wasn’t shown to be effective for these uses. Instead, doctors prescribe the drug to decrease the underlying symptoms of depression that lead to suicidal thoughts.

Also, Spravato isn’t approved for anesthetic purposes like ketamine. (An anesthetic causes a loss of sensation, such as during surgery.) In studies, Spravato wasn’t proven to be safe and effective as an anesthetic drug.

Your doctor will explain how you should take a dose of Spravato. You’ll take each Spravato dose under the supervision of your doctor or another healthcare professional. They’ll explain how much to administer and how often. Be sure to follow your doctor’s instructions.

Taking Spravato

Spravato comes as a nasal (nose) spray that you’ll administer yourself under the guidance of a doctor at a healthcare facility. Your Spravato treatment schedule depends on the medical condition you are taking it to treat.

After you take each dose of Spravato, your doctor or another healthcare professional will monitor you for at least 2 hours. They will also assess you before you’re able to leave the facility.

Accessible medication containers and labels

If it’s hard for you to read the label on your prescription, tell your doctor or pharmacist. Certain pharmacies may provide medication labels that:

  • have large print
  • use braille
  • contain a code you can scan with a smartphone to change the text into audio

Your doctor or pharmacist may be able to recommend a pharmacy that offers these options if your current pharmacy doesn’t.

Taking Spravato with other drugs

Your doctor will prescribe Spravato with at least one other antidepressant that you’ll take by mouth. Examples of these drugs include:

Some people may need to use a nasal corticosteroid such as mometasone (Nasonex) or a nasal decongestant such as oxymetazoline (Kovanaze) for an upper respiratory infection or allergy. Because these are also nasal sprays, it is important to take these medicines at least 1 hour before taking a Spravato dose.

Questions about taking Spravato

Below are some common questions about taking Spravato.

  • Should I take a Spravato dose with food? You should avoid eating for at least 2 hours before taking a Spravato dose. This is because Spravato can cause nausea or vomiting, so it’s best to take a dose on an empty stomach. Your doctor may also recommend that you avoid drinking any liquids 30 minutes before you take a dose.
  • Is there a best time of day to take Spravato? No, there isn’t a best time of day to take a Spravato dose. Your doctor will schedule your appointment to take a Spravato dose under medical supervision.
Questions for your doctor

You may have questions about Spravato and your treatment plan. It’s important to discuss all your concerns with your doctor.

Here are a few tips that might help guide your discussion:

  • Before your appointment, write down questions such as:
    • How will Spravato affect my body, mood, or lifestyle?
  • Bring someone with you to your appointment if doing so will help you feel more comfortable.
  • If you don’t understand something related to your condition or treatment, ask your doctor to explain it to you.

Remember, your doctor and other healthcare professionals are available to help you. And they want you to get the best care possible. So don’t be afraid to ask questions or offer feedback on your treatment.

Some important things to discuss with your doctor when considering Spravato treatment include your overall health and any medical conditions you may have.

Tell your doctor if you’re taking other medication. This is important because some drugs can interfere with Spravato. These and other considerations to discuss with your doctor are described below.

Interactions

Using a medication with certain vaccines, foods, and other things can affect how the medication works. These effects are called interactions.

Before you start treatment with Spravato, be sure to tell your doctor about all medications you take, including prescription and over-the-counter types. Also, describe any vitamins, herbs, or supplements you use. Sharing this information can help you avoid potential interactions.

For information about drug-condition interactions, see the “Other warnings” section below.

Interactions with drugs or supplements

Spravato can interact with several types of drugs. These drugs include:

This list does not contain all types of drugs that may interact with Spravato. Your doctor or pharmacist can tell you more about these interactions and any others that may occur with Spravato treatment.

Boxed warnings

Spravato has three boxed warnings. A boxed warning is the most serious warning from the Food and Drug Administration (FDA) about drug effects that may be dangerous.

Boxed warnings for Spravato include:

Risk of misuse. Spravato is a controlled substance. It’s classified as a Schedule III drug. This means Spravato has a medical use but also has a high risk of dependence. (With dependence, your body needs a drug to feel like it usually does.) Spravato also has a boxed warning for misuse. (With misuse, a drug is taken in a way other than how it’s prescribed.)

People who’ve misused other drugs before may have an increased risk of misusing Spravato. Before prescribing Spravato, your doctor will assess your risk of misuse with Spravato. And during treatment, your doctor will monitor you for signs of misuse.

To help lower the risk of misuse of Spravato, it’s only available through a risk evaluation and mitigation strategy (REMS) program. Through the Spravato REMS program, the healthcare center and pharmacy must be certified to dispense Spravato. To learn more about the requirements of Spravato REMS, visit the program’s website or call855-382-6022.

Risk of sedation, dissociation, and respiratory depression. In studies, sedation (extreme sleepiness) was a common side effect of Spravato. Loss of consciousness was also a possible side effect of Spravato, but reports of this were rare. Another common side effect of Spravato is dissociation (feeling disconnected from time or space or having hallucinations). Spravato may also cause respiratory depression (slow and ineffective breathing), but it isn’t clear how often this side effect occurred. (Respiratory depression wasn’t reported in studies, but it has occurred since the drug was approved.)

You’ll take your dose of Spravato in a healthcare setting and remain under supervision for at least 2 hours after each dose. Your doctor will monitor you closely for sedation if you’re taking other drugs that depress the central nervous system. They will also assess you for changes to your breathing, which will include checking your blood oxygen levels. Spravato is also only available through a REMS program.

Risk of suicidal thoughts and behaviors. Children and young adults (ages 24 years and younger) have a risk of suicidal thoughts and behaviors with Spravato. It’s important to note that Spravato is only approved for use in adults. Your doctor will closely monitor you for suicidal thoughts and behaviors during your treatment with Spravato.

The risk of suicidal thoughts and behaviors is higher than usual when you start treatment and have a dosage change. Your doctor may need to make changes to your treatment plan if you’re having suicidal thoughts and behaviors.

Symptoms of suicidal thoughts and behaviors can include:

  • worsening of depression
  • sudden thoughts of suicide
  • talking about or attempting suicide

Help is out there

If you or someone you know is in crisis and considering suicide or self-harm, please seek support:

If you’re calling on behalf of someone else, stay with them until help arrives. You may remove weapons or substances that can cause harm if you can do so safely.

If you are not in the same household, stay on the phone with them until help arrives.

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Other warnings

Spravato may not be right for you if you have certain medical conditions. These are known as drug-condition interactions. Other factors may also affect whether Spravato is a good treatment option for you.

Talk with your doctor about your health history before starting treatment with Spravato. Factors to consider include those described below.

Heart problems. If you have heart problems, Spravato may not be right for you. Your doctor will weigh the benefits of taking Spravato with the risks to your heart and blood vessels.

Spravato can increase your blood pressure. Depending on the type and severity of your heart condition, an increase in blood pressure may put you at risk for worsening heart-related symptoms. Your doctor will check your blood pressure before you take a dose of Spravato. If your blood pressure is too high, your doctor may delay your dose. Your doctor or another healthcare professional will monitor your blood pressure for about 2 hours after you take a dose.

Allergic reaction. If you’ve had an allergic reaction to Spravato or any of its ingredients, your doctor will likely not prescribe Spravato. Ask them what other medications are better options for you.

Liver problems. If you have liver problems, such as liver disease, talk with your doctor before starting Spravato treatment. Your liver is responsible for clearing Spravato from your body. If your liver isn’t working properly, Spravato levels may build up in your body.

It’s not known if Spravato is safe for people with severe liver failure. If you have moderate liver failure, you may be able to receive treatment with Spravato. However, your doctor may monitor you more closely for side effects and for a longer period.

Psychosis. Both psychosis and Spravato can cause dissociation. If you’ve had psychosis, your doctor will determine whether Spravato is right for you. If your doctor prescribes Spravato, they will closely monitor you for symptoms of dissociation during your treatment.

Bleeding in the brain. If you’ve had bleeding in your brain, your doctor will likely not prescribe Spravato for you. Bleeding in the brain is a contraindication to taking Spravato. (A contraindication is a factor or condition that could prevent your doctor from prescribing a drug due to risk of harm.) Spravato can cause increased blood pressure, and this can raise the risk of another bleed in your brain.

Arteriovenous malformation. If you have an arteriovenous malformation or other types of aneurysmal vascular diseases, your doctor will likely not prescribe Spravato for you. These malformations of the veins and arteries are contraindications to taking Spravato. (A contraindication is a factor or condition that could prevent your doctor from prescribing a drug due to risk of harm.)

Spravato can increase your blood pressure. A change in pressure may cause a malformation to burst and bleed into the brain.

Spravato and alcohol

If you drink alcohol, talk with your doctor about how much (if any) may be safe to drink during your Spravato treatment. This is important because drinking alcohol while taking Spravato can slow brain activity and cause sedation (extreme sleepiness). Combining Spravato with alcohol can raise the risk of sedation, poor concentration, and confusion.

If you’ve ever misused alcohol in the past, let your doctor know. Because there’s also a risk of misuse and dependence with Spravato, you and your doctor can determine if it’s the right medication for you.

If your doctor prescribes Spravato, they may need to closely monitor you for signs of misuse and dependence during treatment.

Pregnancy and breastfeeding

Spravato treatment is not safe during pregnancy and may cause harm to the fetus. If you can become pregnant, talk with your doctor about using birth control during your Spravato treatment.

Before starting Spravato treatment, tell your doctor if you’re pregnant or planning a pregnancy. Your doctor will discuss your options and determine whether Spravato is right for you.

If you become pregnant during treatment with Spravato, tell your doctor right away. It is recommended to stop the medication immediately. But it’s also important to note that discontinuing an antidepressant drug during pregnancy may cause depression symptoms to return. That’s why your doctor will likely discuss other options to treat your depression during pregnancy.

If you do take Spravato during pregnancy, consider enrolling in the drug’s pregnancy registry. Data collected from pregnancy registries help researchers better understand a drug’s risks if taken during pregnancy. To sign up or learn more, visit the registry’s website or call 1-866-961-2388.

It is not safe to take Spravato while breastfeeding. The drug passes into breast milk, and it’s unknown what effects it could have on a child who is breastfeeding. If you’re breastfeeding or planning to breastfeed, talk with your doctor about your options.

Spravato has an increased risk of misuse. (With misuse, a drug is taken in a way other than how it’s prescribed.) In fact, the drug has a boxed warning for the risk of misuse. A boxed warning is the most serious warning from the FDA.

Spravato is also a controlled substance. It’s classified as a Schedule III drug. This means Spravato has a medical use but also has an increased risk of dependence. (With dependence, your body needs a drug to feel like it usually does.)

People who’ve misused or had a dependency on other drugs or alcohol before may have an increased risk of misuse or dependence with Spravato.

To learn more about the boxed warning for misuse, see the “What should be considered before taking Spravato?” section above.

Do not take more Spravato than your doctor prescribes. Taking more than this can lead to serious side effects. If you take too much Spravato, your doctor will closely monitor you for signs and symptoms of overdose.

What to do in case you take too much Spravato

Call your doctor if you think you’ve taken too much Spravato. You can also call 800-222-1222 to reach America’s Poison Centers or use its online resource. But if you have severe symptoms, immediately call 911 or your local emergency number. Or go to the nearest emergency room.

If you have questions about taking Spravato, talk with your doctor or pharmacist. Your doctor can tell you about other treatments you can use for your condition. You can also check out these articles to learn more about depression treatment and for questions you may want to ask your doctor about your depression symptoms.

Some questions to ask your doctor about Spravato may include:

  • What’s the success rate of Spravato treatment?
  • Which natural remedies can I take with Spravato to improve my mood?
  • Can I drive after my Spravato treatment appointment?
  • If I vomit after taking a dose of Spravato, do I need to take another dose?

To learn more about Spravato, see these articles:

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

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