Spravato (esketamine) is a brand-name nasal spray that’s prescribed for certain types of depression in adults. As with other drugs, Spravato can cause side effects, such as nausea and increased blood pressure.

Spravato can cause certain side effects, some of which are more common than others. They can vary depending on the condition the drug is prescribed for. These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

Spravato is prescribed in combination with an oral antidepressant, such as Zoloft (sertraline) or Prozac (fluoxetine). Keep in mind that some side effects may be due to the oral antidepressant rather than Spravato.

These are just a few of the more common side effects reported by people who received Spravato in clinical trials:

  • dizziness
  • vertigo (feeling of dizziness and spinning)
  • nausea*
  • loss of feeling in part of the body*
  • dissociation*†
  • sedation*†

* For more information about this side effect, see “Side effect specifics” below.
† Spravato has a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Mild side effects can occur with Spravato. These side effects can vary depending on which condition the drug is prescribed for. This list does not include all possible mild side effects of the drug. For more details, you can refer to Spravato’s prescribing information.

Spravato is prescribed in combination with an oral antidepressant. Keep in mind that some side effects may be due to the oral antidepressant rather than Spravato.

Mild side effects that have been reported with Spravato include:

  • dizziness
  • vertigo (feeling of dizziness and spinning)
  • anxiety
  • lethargy (feeling sluggish and unmotivated)
  • feeling drunk
  • irritation or discomfort in the throat or nose
  • headache
  • feeling extremely happy or excited
  • insomnia
  • diarrhea
  • nausea and vomiting*
  • loss of feeling in part of the body*
  • mild sedation*†
  • mild allergic reaction*

These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you develop a side effect with Spravato and want to tell the FDA about it, visit MedWatch.

* For more information about this side effect, see “Side effect specifics” below.
† Sedation is a very common side effect with Spravato. This symptom can be mild. However, it can also be serious. In fact, Spravato has a boxed warning for this side effect. A boxed warning is the most serious warning from the FDA.

Spravato may cause serious side effects, which can vary depending on the condition the drug is prescribed for. The list below may not include all possible serious side effects of the drug. For more details, you can refer to Spravato’s prescribing information.

Spravato is prescribed in combination with an oral antidepressant. Keep in mind that some side effects may be due to the oral antidepressant rather than Spravato.

If you develop serious side effects with Spravato, call your doctor right away. If the side effects seem life threatening or you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Serious side effects that have been reported and their symptoms include:

* For more information about this side effect, see “Side effect specifics” below.
† An allergic reaction is possible with Spravato. However, this side effect wasn’t reported in clinical trials.
‡ Spravato has a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Spravato may cause several side effects. Here are some frequently asked questions about the drug’s side effects and their answers.

Should I expect cardiovascular effects with Spravato?

Spravato may cause side effects that can lead to cardiovascular problems. (Cardiovascular refers to the heart and blood vessels.)

Spravato can increase blood pressure. This was a common side effect in clinical trials of Spravato. When blood pressure becomes very high, it could cause a stroke. A stroke is bleeding or blockage of blood vessels that lead to the brain.

To learn more about blood pressure and Spravato, see “Side effect specifics” below.

Does Spravato cause weight gain?

No. Weight gain is not a side effect of Spravato. Weight gain was not reported in clinical trials of the drug.

Weight gain is a side effect of some other medications that treat depression, such as Abilify (aripiprazole) and Symbyax (fluoxetine/olanzapine).

If you’re concerned about gaining weight, talk with your doctor. They can suggest ways to help you manage your weight.

Will Spravato nasal spray ease pain like ketamine does?

Spravato is not approved to treat pain. An anesthetic drug similar to Spravato called Ketalar (ketamine) is sometimes used to lessen pain from certain injuries. Although Spravato and ketamine are similar chemically, they can impact the body in different ways.

Instead, Spravato is approved by the Food and Drug Administration (FDA) to treat the following in certain situations:

Spravato is prescribed in combination with an oral antidepressant.

If you’re experiencing pain, talk with your doctor about possible treatment options.

Are hallucinations a side effect of Spravato?

Yes, some people have had hallucinations after a dose of Spravato. (Hallucinations refer to experiences in which you see, hear, or feel things that aren’t real.) Due to this risk, a healthcare professional will monitor you after you receive the drug.

If you have any concerns about hallucinations and Spravato, talk with your doctor.

Learn more about some of the side effects that Spravato may cause. To find out how often side effects occurred in clinical trials, see the prescribing information for Spravato.

Nausea and vomiting

Spravato can cause nausea and vomiting. In clinical trials, these were common side effects. They usually occur the day you receive your dose and do not tend to last longer than 1 hour. The nausea and vomiting should ease with future doses.

What you can do

To help prevent nausea and vomiting, avoid eating 2 hours before your dose of Spravato. You should also stop drinking liquids about 30 minutes before your dose.

If you have concerns about nausea and vomiting with Spravato, talk with your doctor.

Increased blood pressure

Spravato can cause increased blood pressure. The increase usually starts about 40 minutes after a dose and lasts around 4 hours. In clinical trials, increased blood pressure was a common side effect.

In rare cases, Spravato may cause a hypertensive crisis. This is when blood pressure gets very high. Symptoms can include chest pain and shortness of breath.

Spravato may also cause a condition known as hypertensive encephalopathy. It happens when blood pressure gets extremely high and affects the brain. Symptoms can include:

  • severe headache that starts suddenly
  • problems with vision
  • seizures
  • loss of consciousness
  • problems with your nervous system, which includes the nerves, brain, and spine

Hypertensive crisis and hypertensive encephalopathy are medical emergencies.

What you can do

After you receive a dose of Spravato, a healthcare professional will monitor your blood pressure for at least 2 hours to make sure it’s not increasing rapidly. If you have had a hypertensive crisis or hypertensive encephalopathy in the past, they’ll likely monitor you more closely than usual. They’ll look for changes in blood pressure and other symptoms.

If you develop high blood pressure with Spravato, you’ll likely receive medication to help lower it.

Loss of feeling in part of the body

People receiving Spravato in clinical trials commonly experienced loss of feeling in different parts of the body. This included losing feeling in the mouth, throat, nose, and teeth. It’s unknown how long they had these symptoms. However, these are mild side effects, which usually go away after a few days.

What you can do

If the symptoms do not go away after a few days, talk with your doctor. They can help determine whether Spravato is the cause and if the drug is right for you. Be sure to tell your doctor if you have had loss of feeling in parts of your body in the past.

Serious bladder problems

Spravato may cause bladder problems such as:

  • pain when urinating
  • increased urge to urinate
  • urinating more often during the day and at night
  • bladder infection

These bladder problems are usually mild. They should go away after a few days or after brief treatment from your doctor.

There have been reports of a bladder condition called interstitial cystitis in people who misused Ketalar (ketamine), which is a drug similar to Spravato. There have not been any reported cases of interstitial cystitis with Spravato. Misuse refers to taking a drug in a way other than how your doctor prescribed.

What you can do

Be sure to talk with your doctor if you develop any bladder problems during Spravato treatment. They can help determine if you need treatment.

Allergic reaction

As with most drugs, Spravato can cause an allergic reaction in some people. However, this side effect was not reported in clinical trials.

Symptoms can be mild or serious and can include:

  • skin rash
  • itching
  • flushing
  • swelling under your skin, typically in your lips, eyelids, feet, or hands
  • swelling of your mouth, tongue, or throat, which can make it hard to breathe

What you can do

For mild symptoms of an allergic reaction, call your doctor right away. They may recommend ways to ease your symptoms and determine whether you should keep receiving Spravato. If your symptoms are serious and you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Boxed warnings

Spravato has boxed warnings about several risks. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). Spravato’s boxed warnings are about risks of misuse, respiratory depression, dissociation, sedation, and suicidal thoughts and behaviors.

Because of the seriousness of these boxed warnings, Spravato is available only through a restricted program called Spravato REMS. This stands for risk evaluation and mitigation strategy. To distribute Spravato, the doctor’s office and pharmacy must be part of the program. You’ll be enrolled as well. The goal is to help make sure Spravato is given safely. Find additional information about Spravato REMS by visiting the program website or calling 855-382-6022.

Risk of misuse. Spravato has the potential for misuse, which refers to taking a drug in a way other than how your doctor prescribed. Misuse wasn’t a common side effect in clinical trials.

Risk of respiratory depression. Spravato has a boxed warning about the risk of respiratory depression, which means a slow, shallow breathing rate. This side effect wasn’t reported in clinical trials, but it has occurred since the drug was approved.

Risk of dissociation. Spravato may cause dissociation, which means feeling disconnected from your mind, your body, time, or space. You may see or hear things that aren’t real or feel like your mind and body aren’t connected. Dissociation was a very common side effect in clinical trials.

Risk of sedation. Spravato may cause sedation, which means the drug can make you feel extremely sleepy. This was a very common side effect in clinical trials. In rare cases, people became so sedated that they lost consciousness.

Risk of suicidal thoughts and behaviors. Spravato, like other antidepressants, carries a boxed warning about an increased risk of suicidal thoughts and behaviors. In the clinical trials of other antidepressants, this side effect occurred in adults ages 24 years and younger and in children. (Spravato is not approved to be prescribed for children.)

Antidepressants are typically used to treat depression. However, they can also cause changes in mood and other unwanted side effects that may increase the risk of suicidal thoughts and behaviors.

What you can do

Here’s some information on steps you and your doctor can take to help prevent problems related to boxed warnings.

What you can do about the risk of misuse. Your doctor will monitor you for signs of misuse during Spravato treatment. Your risk of misuse may be increased if you have misused drugs or alcohol in the past. It’s important to talk with your doctor if you have a history of substance misuse. To learn more, see “Spravato and misuse” below.

What you can do about the risk of respiratory depression. After you receive a dose of Spravato, a healthcare professional will monitor you for at least 2 hours. This will include checking your blood oxygen levels. They’ll complete an assessment to make sure you’re alert and that it’s safe for you to leave. Make sure to tell the healthcare professional if you experience any symptoms of respiratory depression, which can include:

  • shortness of breath
  • frequent yawns
  • confusion

What you can do about the risk of dissociation. After you receive a dose of Spravato, a healthcare professional will monitor you for at least 2 hours. They’ll complete an assessment to make sure you’re alert and that it’s safe for you to leave. Be sure to tell them if your perception of time or space changes. You should also mention whether you see, hear, or feel things that aren’t real.

Before you start Spravato treatment, it’s important to tell your doctor if you’ve had psychosis in the past. (Psychosis is a mental disorder in which you lose touch with reality.) This could increase your risk of dissociation. To learn more, see “Precautions for Spravato” below.

What you can do about the risk of sedation. After you receive a dose of Spravato, a healthcare professional will monitor you for at least 2 hours. They’ll complete an assessment to make sure you’re alert and that it’s safe for you to leave. It’s important to let them know if you have any symptoms of sedation, which can include:

  • feeling extremely sleepy
  • not being able to think clearly
  • not being alert enough to drive or use heavy machinery

You’ll need to have someone, such as a family member or trusted friend, drive you home after your dose.

What you can do about the risk of suicidal thoughts and behaviors. During Spravato treatment, your doctor will monitor you for the symptoms of suicidal thoughts and behaviors, which can include:

  • depression that gets worse
  • thoughts of suicide
  • suicide attempts

You, your friends, and your loved ones should also watch for these symptoms. If you develop any symptoms, immediately talk with your doctor or seek emergency care.

Suicide prevention

If you know someone at immediate risk of self-harm, suicide, or hurting another person:

  • Ask the tough question: “Are you considering suicide?”
  • Listen to the person without judgment.
  • Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.
  • Stay with the person until professional help arrives.
  • Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The 988 Suicide and Crisis Lifeline is available 24 hours a day at 988. During a crisis, people who are hard of hearing can use their preferred relay service or dial 711 then 988.

Find more links and local resources.

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This drug comes with several warnings and precautions.

Boxed warnings

Spravato has several boxed warnings. Boxed warnings are the most serious warnings from the Food and Drug Administration (FDA). Spravato’s boxed warnings are about the following:

Other precautions

Be sure to talk with your doctor about your health history before starting Spravato treatment. Spravato may not be right for you if you have certain medical conditions or other factors that affect your health. The conditions and factors to consider include:

  • Psychosis. Spravato may cause dissociation (feeling disconnected from your mind, your body, time, or space). If you have had psychosis in the past, tell your doctor before starting Spravato treatment. You may have an increased risk of a severe dissociative or psychotic event if you receive the drug. Your doctor can help determine whether Spravato is right for you.
  • Substance misuse. If you have misused drugs or alcohol in the past, be sure to tell your doctor before you receive Spravato. Your risk of misuse with Spravato may be increased. The drug has a boxed warning about misuse. To learn more, see “Spravato and misuse” below.
  • Liver disease. If you have liver problems, talk with your doctor before starting Spravato treatment. You may have an increased risk of side effects from the medication. This risk can last for a long time after you receive Spravato. You may need to be monitored for longer than 2 hours after your doses if you have moderate liver disease.
  • High blood pressure. Spravato can increase blood pressure. This can affect your heart, blood vessels, and brain. If you have high blood pressure, talk with your doctor about whether Spravato is safe.

A contraindication is a factor or condition that could prevent your doctor from prescribing a drug due to risk of harm. Spravato is contraindicated (typically not prescribed) if you have:

  • Aneurysms or certain blood vessel problems. Spravato can increase blood pressure. In severe cases, this may lead to serious bleeding events, such as stroke. This risk is increased if you have or have had an arteriovenous malformation or aneurysmal vascular disease (AVD). AVD occurs when the wall of a blood vessel gets weak and balloons out. Be sure to tell your doctor if you have had these problems.
  • Brain bleed. Spravato can cause a rise in blood pressure that affects the brain. This can increase the risk of bleeding inside your brain. Tell your doctor if you have had any bleeding in your brain in the past.
  • Allergy to ketamine. If you’ve had an allergic reaction to Ketalar (ketamine), ask your doctor what other medications may be better options for you. Ketamine is similar to Spravato, so if you’re allergic to ketamine, you may be allergic to Spravato.
  • Allergy to Spravato or its ingredients. If you’ve had an allergic reaction to Spravato or any of its ingredients, ask your doctor about other medications that may be better for you.

Alcohol and Spravato

Drinking alcohol during Spravato treatment is not recommended. Consuming alcohol with the drug can increase your risk of sedation.

Sedation refers to a feeling of extreme sleepiness. In fact, Spravato has a boxed warning about the risk of sedation. A boxed warning is the mostserious warning from the Food and Drug Administration (FDA). To learn more, see “Side effect specifics” above.

Pregnancy and breastfeeding during Spravato treatment

Spravato treatment is not safe while you’re pregnant or breastfeeding. The drug may harm a fetus or a child who is breastfed. Be sure to tell your doctor if you’re pregnant or breastfeeding. They can let you know about other treatment options for your condition.

If you’re prescribed Spravato during pregnancy, consider enrolling in a pregnancy registry. This registry helps collect information about the drug’s safety during pregnancy. For additional information, talk with your doctor. You can also visit the registry website or call 866-961-2388.

Spravato has a boxed warning about the risk of misuse. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Misuse refers to taking a drug in a way other than how your doctor prescribed. Spravato has the potential for misuse.

Because of the seriousness of the misuse boxed warning, Spravato is available only through a restricted program called Spravato REMS. This stands for risk evaluation and mitigation strategy. To distribute Spravato, the doctor’s office and pharmacy must be part of the program. You’ll be enrolled as well. The goal is to help make sure Spravato is given safely.

Your doctor will monitor you for signs of misuse during Spravato treatment. You may be at an increased risk of misuse if you have misused drugs or alcohol in the past. To learn more, see “Precautions for Spravato” above. You can also find additional information about Spravato REMS by visiting the program website or calling 855-382-6022.

Treatment with Spravato can cause mild and serious side effects. Many of the common side effects are mild. However, Spravato can cause serious side effects in some cases. Talk with your doctor if you develop side effects that are serious or bother you.

If you’d like to learn more about Spravato, talk with your doctor or pharmacist. They can help answer any questions you have about side effects of the drug.

Besides talking with your doctor, you can do some research on your own. These articles might help:

  • More information about Spravato. For details about other aspects of Spravato, refer to this article.
  • Drug comparison. To learn how Spravato compares with Abilify and Symbyax, read the “Spravato vs. other drugs” section in this article.
  • Dosage. For information about the dosage of Spravato, view this article.
  • A look at depression. If you’d like to learn more about your condition, see our mental health hub and list of articles about depression.

Disclaimer: Medical News Today 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.