Spravato Overview: Side Effects, Uses, Dosage, and More

Health Line

23-05-2025

Spravato (esketamine) is a prescription drug that's approved to treat certain forms of depression. Esketamine comes as a nasal spray that you inhale.
Specifically, Spravato is approved by the Food and Drug Administration (FDA) to treat the following conditions in adults:
treatment-resistant depression, alone or in conjunction with an oral antidepressant
depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or behavior, in conjunction with an oral antidepressant
To learn more about Spravato's uses, see the ' Uses for Spravato ' section.
Spravato basics
Spravato is a brand-name medication. It contains the active ingredient esketamine. A generic version of the drug isn't currently available.
Spravato has boxed warnings. A boxed warning is the most serious warning from the FDA. For details, see the ' Spravato precautions ' section.
Uses for Spravato
Spravato is used to treat the following forms of depression in adults.
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 behavior
Spravato is also approved for adults with major depressive disorder (MDD) with suicidal thoughts or behavior.
Symptoms of major depressive disorder include:
persistent low mood
little interest in activities you used to enjoy
feelings of guilt or worthlessness
fatigue
difficulty focusing
increase or decrease in appetite
insomnia
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.
Side effects of Spravato
Like most drugs, Spravato may cause mild or serious side effects. The following lists contain 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.
Note: After the FDA approves a drug, it tracks and reviews side effects of the medication. Sharing your experience helps make medications safer for everyone by giving doctors and researchers more information about how the drug works in real life. If you develop a side effect while taking Spravato and want to tell the FDA about it, visit MedWatch or call 800-FDA-1088.
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
excessive sweating
irritation and discomfort in the nose or throat
muscle pains
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.
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:
difficulty with attention, judgment, thinking, reaction speed, and motor skills
increased blood pressure, which may lead to serious events such as stroke or seizures
serious bladder or urinary tract problems, such as inflammation of your bladder
boxed warnings:
For more about Spravato's boxed warnings, see the ' Spravato precautions ' section.
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.
Spravato dosage
The Spravato dosage your doctor prescribes will depend on several factors. These include:
the type and severity of the condition you're using Spravato to treat
your age
other medical conditions you may have
The following information describes dosages that are commonly used or recommended. However, be sure to use the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.
Form and strength
Spravato comes as a solution in a nasal 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 behavior, 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.
How to use Spravato
Spravato comes as a nasal 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.
Questions about using Spravato
Below are answers to some common questions about using Spravato.
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.
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.
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 or behavior, their depression symptoms began to ease after 4 hours. Depression symptoms continued to decrease over the next 4 weeks of treatment in both groups.
Using 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:
venlafaxine (Effexor XR)
escitalopram (Lexapro)
bupropion (Wellbutrin SR, Wellbutrin XL)
mirtazapine (Remeron)
amitriptyline
Some people may need to use a nasal corticosteroid such as mometasone (Nasonex) or a nasal decongestant such as oxymetazoline (Afrin) 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.
Overdose
Do not take more Spravato than your doctor prescribes, as this can lead to harmful effects.
What to do in case of overdose
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.
Spravato interactions
Using a medication with certain vaccines, foods, and other things can affect how the medication works. These effects are called interactions.
Spravato can interact with several other medications. It can also interact with certain supplements as well as certain foods.
Before using Spravato, talk with your doctor and pharmacist. Tell them about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, or supplements you use. Sharing this information can help you avoid potential interactions.
Spravato cost and coupons
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 your cost for the drug.
Factors to consider when using Spravato
Pregnancy and Spravato
Spravato should not be used during pregnancy. If you're planning a pregnancy or can become pregnant, talk with your doctor before using this drug. Your doctor may suggest birth control options to use during treatment with Spravato.
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 866-961-2388.
Spravato and breastfeeding
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 breastfed. If you're breastfeeding or planning to breastfeed, talk with your doctor about your options.
Spravato precautions
The following is important information to consider and discuss with your doctor or pharmacist before using Spravato.
FDA warnings
Spravato has three boxed warnings. A boxed warning is the most serious warning from the 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 call 855-382-6022.
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:
Help is out there
If you or someone you know is in crisis and considering suicide or self-harm, please seek support:
Call or text the 988 Suicide and Crisis Lifeline at 988 or chat at 988lifeline.org. Caring counselors are available to listen and provide free and confidential support 24/7.
Text HOME to the Crisis Text Line at 741741 to connect with a volunteer crisis counselor for free and confidential support 24/7.
Not in the United States? Find a helpline in your country with Befrienders Worldwide.
Call 911 or your local emergency services number if you feel safe to do so.
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're not in the same household, stay on the phone with them until help arrives.
Other precautions
Before using Spravato, discuss your health history with your doctor. Spravato may not be right for you if you have certain medical conditions or other factors affecting your health. Be sure to talk with your doctor if any of the following apply to you:
heart problems
high blood pressure
liver problems
psychosis
bleeding in the brain
arteriovenous malformation
previous allergic reaction to this or a similar drug
Spravato misuse and dependence
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.
Frequently asked questions about Spravato
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 ' Factors to consider when using Spravato ' section.
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.