Spravato (esketamine) is a prescription drug that’s approved to treat depression in certain situations. Spravato can cause side effects that range from mild to serious. Examples include dizziness and nausea.

Specifically, Spravato is prescribed to treat the following in adults:

For these conditions, doctors will prescribe Spravato with another antidepressant (one you’ll take by mouth).

The active ingredient in Spravato is esketamine. (An active ingredient is what makes a drug work.) The drug comes as a nasal (nose) spray that you’ll give yourself under the guidance of a doctor at a healthcare facility.

Keep reading to learn about the common, mild, and serious side effects that Spravato can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may experience mild to serious side effects during their Spravato treatment. Examples of Spravato’s commonly reported side effects include:

While these were the most common side effects reported in Spravato’s studies, it’s important to note that they won’t happen to everyone who uses this drug. And these are just a few side effects Spravato may cause. Read on for more information about other possible side effects of this drug.

* Spravato has a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects explained” section below.

Like most medications, Spravato can cause mild side effects. Examples that have been reported include:

In most cases, these side effects should be temporary. And some may be easily managed. But if you have symptoms that are ongoing or bother you, talk with your doctor or pharmacist. And don’t stop Spravato treatment unless your doctor recommends it.

Spravato may cause mild side effects other than the ones listed above. See Spravato’s prescribing information for details.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Spravato, visit MedWatch.

* Sedation is very common with Spravato treatment. This side effect can be mild or serious. In fact, Spravato has a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects explained” section below.
To learn more about this side effect, see the “Side effects explained” section below.

Serious side effects are possible with Spravato treatment. Serious side effects that have been reported include:

If you develop serious side effects during Spravato treatment, 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.

* To learn more about this side effect, see the “Side effects explained” section below.
To learn more about the risk of misuse, see the “Spravato and misuse” section below.
‡ An allergic reaction is possible after using Spravato. But this side effect wasn’t reported in studies.

Get answers to some frequently asked questions about Spravato’s side effects.

Can Spravato cause long-term side effects?

It’s possible, but it’s not known for sure. In studies, both mild and severe side effects were reported on the day Spravato was taken. But these side effects typically went away on the same day.

It isn’t known for certain whether taking Spravato long term may raise the risk of specific side effects.

If you’re concerned about possible long-term side effects from Spravato, talk with your doctor or pharmacist.

Does Spravato cause weight gain?

No, weight gain wasn’t a side effect reported in people using Spravato in the drug’s studies.

Other medications used to treat depression may cause weight gain as a side effect. Examples of these include:

You may take Spravato alone or with other medications for treating depression. It’s possible that other medications you take for this condition may cause weight gain as a side effect. Your doctor or pharmacist can tell you more about antidepressants that are less likely to cause weight gain.

Is Spravato addictive?

Treatment with Spravato may cause dependence, and it’s possible to misuse this drug. But addiction wasn’t a side effect reported in the drug’s studies.

It’s important to note the difference between dependence, addiction, and misuse:

  • With dependence, your body needs the drug to feel like it usually does. Dependence wasn’t reported in Spravato studies, but it has happened when people have used ketamine frequently and for a long time. (Spravato contains the active drug esketamine, which is very similar to ketamine.)
  • Addiction refers to feeling unable to stop using a drug, even though it may be causing harm.
  • Drug misuse means taking a drug in a way other than how a doctor prescribes it.

Spravato has a boxed warning for risk of misuse. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Spravato and misuse” section below.

Speak with your doctor or pharmacist if you’d like to learn more about Spravato and drug dependence, addiction, and misuse.

Learn more about some of the side effects Spravato may cause.

Risk of sedation, disassociation, and respiratory depression

Spravato has a boxed warning about the risk of sedation, dissociation, and respiratory depression. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about the most serious side effects that drugs such as Spravato may cause.

Spravato may cause feelings of sedation (extreme sleepiness). The drug may also cause dissociation (feeling disconnected from yourself or your thoughts). It’s also possible to experience respiratory depression (slow and ineffective breathing) with Spravato treatment.

Dissociation was the most common side effect, and sedation was among the most common side effects in Spravato’s studies. In rare cases, sedation led to a loss of consciousness. Respiratory depression wasn’t a side effect that was reported in studies, but it has been reported since the drug was approved.

In addition to feeling disconnected from yourself or your thoughts, dissociation can cause symptoms such as:

Your risk of dissociation from Spravato is higher if you have or have had psychosis.

What might help

Before prescribing Spravato, your doctor will assess your risk of sedation, dissociation, and respiratory depression. If you have received a diagnosis of psychosis, your doctor may decide to prescribe a treatment other than Spravato.

If your doctor prescribes Spravato, you’ll receive doses of the drug in a healthcare setting, such as your doctor’s office or a clinic. Your doctor or another healthcare professional will monitor you for at least 2 hours after each dose. Tell your doctor right away if you feel like you can’t stand up or are going to pass out after getting a dose of Spravato.

After at least 2 hours, your doctor will check in with you to determine when you’re ready to leave the clinic or office. Due to the risk of sedation, you’ll need to have someone else drive you home after getting your Spravato dose. And you should avoid driving or operating machinery on the day of your treatment. Only resume these activities after waiting at least 1 day and getting a full night’s sleep.

Due to the risk of respiratory depression, your doctor or the healthcare professional will also monitor your breathing for at least 2 hours after a dose of Spravato. This will include checking your blood oxygen levels.

Risk of suicidal thoughts and behaviors

Spravato has a boxed warning about the risk of suicidal thoughts and behaviors. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about the most serious side effects that drugs such as Spravato may cause.

Like other antidepressant drugs, Spravato can increase the risk of suicidal thoughts and behaviors in people ages 24 years and younger. (Spravato is only approved for adults ages 18 years and older.) This risk is highest during the first few months of treatment or when the dose is changed.

Suicidal thoughts were reported in Spravato’s studies, but this side effect was not common. Self-harm was rare in these studies when the drug was used in adults with depression who were actively having suicidal thoughts or behaviors.

It’s important to note that having depression is also a risk factor for suicidal thoughts and behaviors.

What might help

Your doctor will monitor you for worsening depression or suicidal thoughts or behaviors throughout your treatment with this drug. You should also let loved ones or friends know that you are taking Spravato to treat your depression. They can help watch for changes in your mood.

If you develop suicidal thoughts or behaviors during treatment with Spravato, your doctor may suggest stopping this drug.

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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Temporary increase in blood pressure

You may have a temporary increase in blood pressure after receiving a dose of Spravato.

In studies, these increases were highest about 40 minutes after getting a dose. They lasted about 4 hours on average. In some instances, these increases were high enough to cause concern.

Mild increases in blood pressure don’t usually cause symptoms. But if your blood pressure becomes high enough, it could cause serious symptoms such as:

Due to these risks, doctors usually won’t prescribe Spravato for people with certain conditions that an increase in blood pressure could seriously worsen. These conditions include:

Your doctor can explain the risks and benefits of Spravato if you have certain other medical conditions that an increase in blood pressure could worsen. These include:

What might help

Before starting Spravato treatment, tell your doctor about any medications you take and the conditions you may have. Your doctor can help determine whether this drug is safe for you.

Before each dose of Spravato, your doctor will check your blood pressure. If your blood pressure reading is high that day, your doctor may delay your dose until it returns to acceptable levels for you.

After each dose of Spravato, your doctor or another healthcare professional will monitor you for at least 2 hours. This includes monitoring your blood pressure. If you have symptoms of dangerously high blood pressure or a very high reading, they can refer you for emergency care. This may involve treatment in an emergency room or hospital.

Cognitive impairment

Spravato treatment may cause cognitive impairment. But this side effect was temporary in the drug’s studies, peaking about 40 minutes on average after people received a dose. This side effect went away after about 1 to 2 hours. Long-term cognitive impairment wasn’t reported in anyone during Spravato’s studies.

But long-term cognitive impairment has happened in people who have used ketamine frequently and for a long time. (Spravato contains the active drug esketamine, which is very similar to ketamine).

Symptoms of cognitive impairment can include:

  • memory problems
  • difficulty with concentrating or carrying out tasks, such as planning your day or doing math

What might help

After each dose of Spravato, your doctor or another healthcare professional will monitor you for at least 2 hours. This includes monitoring your cognition, which they’ll confirm is satisfactory before clearing you to leave. You should avoid driving or operating machinery on the day you receive a Spravato dose. Only resume these activities after waiting at least 1 day and getting a full night’s sleep. This is to be sure your cognition returns to how it was before you took your dose.

Allergic reaction

Like most drugs, Spravato can cause an allergic reaction in some people. But this side effect wasn’t reported in studies.

Symptoms can be mild to serious and can include:

  • skin rash
  • itchiness
  • flushing (temporary warmth, redness, or deepening of skin color)
  • swelling under your skin, usually in your eyelids, lips, hands, or feet
  • swelling of your mouth, tongue, or throat, which can make it hard to breathe

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. They may suggest an over-the-counter oral antihistamine, such as Benadryl (diphenhydramine), or a topical product, such as hydrocortisone cream, to manage your symptoms.

If your doctor confirms you’ve had a mild allergic reaction to Spravato, they’ll decide if you should continue treatment.

If you have symptoms of a severe allergic reaction, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you’ve had a serious allergic reaction to Spravato, they may have you switch to a different treatment.

Keeping track of side effects

During your Spravato treatment, consider taking notes on any side effects you’re having. You can then share this information with your doctor. This is especially helpful when you first start taking new drugs or using a combination of treatments.

Your side effect notes can include things such as:

  • what dose of the drug you were taking when you had the side effect
  • how soon you had the side effect after starting that dose
  • what your symptoms were
  • how it affected your daily activities
  • what other medications you were taking
  • any other information you feel is important

Keeping notes and sharing them with your doctor will help them learn more about how Spravato affects you. They can then use this information to adjust your treatment plan if needed.

Below are important considerations that may affect whether your doctor prescribes Spravato for you. These considerations include several boxed warnings.

Boxed warnings

Spravato has the boxed warnings listed below. Boxed warnings are the most serious warnings from the Food and Drug Administration (FDA).

  • Risk of sedation, dissociation, and respiratory depression. Spravato may cause sedation (extreme sleepiness), dissociation (feeling disconnected from yourself), and respiratory depression (slow and ineffective breathing). Your doctor or another healthcare professional will monitor you for at least 2 hours after each dose of Spravato. Tell your doctor right away if you feel like you can’t stand up or are going to pass out after receiving your dose.
  • Risk of misuse. Spravato can be misused. (Misuse refers to taking a drug in a way other than how a doctor prescribes it.) Due to the risk of misuse, Spravato is only available through a special prescribing program called risk evaluation and mitigation strategy (REMS). Your doctor must have special approval to prescribe it. And you can only receive it in a setting such as their office or a clinic. Your doctor will monitor you for signs of misuse throughout your treatment.
  • Risk of suicidal thoughts and behaviors. Like other antidepressants, Spravato can increase the risk of suicidal thoughts and behaviors in people ages 24 years and younger. (Spravato is only approved for use in adults ages 18 years and older.) This risk is highest during the first few months of treatment or any time the dose is changed.

For details on the risk of misuse, see the “Spravato and misuse” section below. For information on the other boxed warnings shown here, see the “Side effects explained” section above.

Other warnings

Spravato may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before starting Spravato. The list below includes factors to consider.

Brain or heart problems. Treatment with Spravato can cause temporary but large increases in blood pressure. In certain people, elevations in blood pressure can be dangerous. This includes people who have or have had certain brain or heart problems, including a heart attack or bleeding in the brain. Your doctor can help determine whether Spravato is safe for you.

Liver problems. If you have liver problems, you may be at increased risk of side effects from Spravato. And the manufacturer of this drug recommends that people with severe liver problems do not use Spravato. Your doctor can help determine whether this drug is safe for you. They may monitor you more closely if they decide to prescribe it for you.

Mental health condition, including psychosis. Spravato can cause side effects related to mental health, including suicidal thoughts or behaviors. (Spravato has a boxed warning about this side effect, which is discussed in more detail just above.) If you have a mental health condition, such as psychosis, Spravato may not be safe for you. Your doctor can help determine this. And they may monitor you more closely if they decide to prescribe this drug for you.

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

Alcohol and Spravato

If you drink alcohol, you should avoid drinking it on the day you get a dose of Spravato. This is because both Spravato and alcohol can cause sedation (extreme sleepiness). Alcohol can also increase your risk of other side effects from Spravato, such as:

Talk with your doctor about whether it’s safe for you to consume alcohol on days you don’t receive a Spravato dose.

Pregnancy, breastfeeding and Spravato

The manufacturer of Spravato recommends against using the drug if you’re pregnant or breastfeeding. Your doctor can suggest other treatment options for you instead.

If you and your doctor decide you’ll use Spravato during pregnancy, consider joining the National Pregnancy Registry for Antidepressants (NPRAD). Pregnancy registries collect information about the use of certain drugs during pregnancy. To learn more and register, call 866-961-2388 or visit the NPRAD website.

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

Spravato has the potential to be misused. (Misuse refers to taking a drug in a way other than how a doctor prescribes it.) Due to this risk, Spravato is only available through a special prescribing program called risk evaluation and mitigation strategy (REMS). This means you can only receive the drug in a setting such as a doctor’s office or clinic. And your doctor must have special approval to prescribe it for you.

To find more information about the Spravato REMS program, visit the program’s website, call 855-382-6022, or talk with your doctor.

It’s also important to note that Spravato is a controlled substance. A controlled substance refers to a drug that has accepted medical uses but also has a risk of dependence and misuse. (To learn more about drug dependence and misuse, see the question titled “Is Spravato addictive?” in the “FAQs about Spravato’s side effects” section above.)

The U.S. government has laws that govern how controlled substances can be prescribed and dispensed. Your doctor or pharmacist can tell you more about how these laws apply to Spravato.

The risk of misuse is higher if you have or have had a substance use disorder. Be sure to tell your doctor about your entire medical history before starting Spravato, including any history of substance misuse.

Your doctor will monitor you for signs of misuse during your Spravato treatment.

Like most drugs, Spravato can cause side effects that range from mild to serious. Before beginning treatment, talk with your doctor. Ask questions to help you become familiar with this treatment and its side effects.

Some examples to help get you started are:

  • If I have side effects from Spravato, is there a lower dose I can try?
  • Does my medical history put me at increased risk of certain side effects from this drug?
  • Are there ways I can reduce my risk of side effects from Spravato?

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.

Q:

Can other medications increase my risk of side effects from Spravato?

Anonymous

A:

Yes, taking certain other medications during treatment with Spravato may increase your risk of side effects. These include:

This is not a comprehensive list of drugs that may increase your risk of side effects. Before starting Spravato, be sure to tell your doctor about all medications you take. They can check for interactions with Spravato. If you take drugs that can increase your risk of side effects, such as those above, your doctor may:

  • have you stop taking the other medication, or
  • prescribe a medication other than Spravato to treat your depression
The Healthline Pharmacist TeamAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.
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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.