9 Spravato Side Effects to Know About

Recently, ketamine infusions have been in the spotlight as a depression treatment. But at this time, injectable ketamine isn’t FDA-approved for this use.

Spravato (esketamine) is the only FDA-approved ketamine-based treatment for severe or treatment-resistant depression. It comes as a nasal spray that’s administered in the presence of a healthcare professional. Even though Spravato has been called a game changer for fast depression relief, there are still some important side effects to be aware of before you use it. Here’s what you should know.

Spravato side effects at a glance

Below is a list of common and rare Spravato side effects reported in clinical studies as well as real-world use. Most side effects resolve on their own within 2 hours of receiving Spravato. You’ll remain under medical supervision during this time so your healthcare team can manage any side effects that occur. 

Common and mild Spravato side effects include:

• Sleepiness

• Nausea and vomiting

• Dissociation (feeling detached from reality)

• Dizziness

• Vertigo

• Headache

• Lethargy (feeling sluggish or drained of energy)

• Euphoric mood 

• Nose or throat irritation

• Altered taste

• Dry mouth

• Diarrhea or constipation

• Anxiety

• Increased heart rate

• Feeling of intoxication

• Blurred vision

• Numbness to touch

Rare but serious Spravato side effects include:

• High blood pressure

• Hallucinations

• Loss of consciousness

Spravato also has a few boxed warnings, which is the FDA’s most serious drug warning. These include:

• Slowed breathing, dissociation, and sedation after administration

• Potential for abuse and misuse

• Suicidal thoughts and behaviors

Below, we’ll talk more in-depth about nine Spravato side effects and how to manage them.

Good to know: You shouldn’t receive Spravato if you’re pregnant, breastfeeding, or planning to become pregnant. This can cause harm to your baby.

1. Dissociation

Dissociation — feeling disconnected from your mind or body — is a common Spravato side effect, especially after your first few doses. Dissociation symptoms tend to peak 30 to 40 minutes after receiving your dose and go away after 2 hours in most cases. The feeling is usually mild but can cause anxiety for some people. And in rare cases, more severe dissociation symptoms occur, including hallucinations.

A healthcare professional will watch you closely for at least 2 hours after each Spravato dose. Additionally, the following tips might help you during your appointment: 

• Engage in breathing and mindfulness exercises

• Listen to calming music on your phone or other device

• Ask your medical care team if a friend or family member can be with you for support

EXPERT PICKS: WHAT TO READ NEXT

• Treatment-resistant doesn’t mean untreatable: Explore the different options to help improve depression symptoms when other treatments haven’t worked.

• Spravato tips: Learn what to expect during a Spravato treatment and how to get the most from your medication.

• Another fast-acting antidepressant: Here’s how Spravato stacks up to Auvelity, an oral tablet that can begin working in about a week.

Dissociation rarely continues beyond 2 hours. Still, it’s possible to have lingering effects for a day or two. So plan on having a ride home after your Spravato dose. In fact, you should avoid any task that requires alertness for 24 hours.

2. Drowsiness

Drowsiness after receiving Spravato is usually mild and goes away the same day. But Spravato is sometimes prescribed along with oral antidepressants, many of which can cause ongoing drowsiness.

Plan on resting after you get home from your Spravato treatment. Avoid driving or other activities that require alertness. If you live alone, ask a friend or family member to check in on you. And if you still feel more tired than usual a day or two later, let your prescriber know.

It’s also a good idea to avoid other sedating medications while you’re being treated with Spravato unless your prescriber recommends them. Examples include benzodiazepines, opioids, and sleeping pills.

3. Dizziness

You might feel lightheaded after receiving Spravato. A spinning sensation (vertigo) can also occur. After receiving Spravato, lying down might help you cope with dizziness. You’ll remain under medical supervision for at least 2 hours after your dose before you can go home. In most cases, dizziness will pass during this time. But be sure to let your prescriber know if it doesn’t.

On days you receive Spravato, be careful when changing positions — such as standing up from a sitting position — and take it slow. Staying hydrated and eating regularly may help you feel better.

Reach out to your prescriber if dizziness continues the next day or is severe. They may recommend a lower Spravato dose for your next treatment, since dizziness tends to be more likely with higher doses.

4. Nausea and vomiting

It’s common to feel a wave of nausea after receiving Spravato. Vomiting is also possible, but it’s less common. To lower the risk of nausea and vomiting, stop eating at least 2 hours before (and drinking fluids at least 30 minutes before) your Spravato dose.

Let your prescriber know if nausea is an issue for you during your treatment. Some medications, such as Zofran (ondansetron), may help treat nausea caused by Spravato. Or your prescriber may recommend taking it before your Spravato dose to prevent nausea.

5. Altered taste and dry mouth

Some people experience a foul or metallic taste in their mouth after receiving Spravato. This may be because the nasal spray can drain into your throat, leaving an aftertaste. Dry mouth, nasal discomfort, and throat irritation are also possible.

Masking the aftertaste with something fruit-flavored may help. Consider bringing juice or a flavored beverage to drink to your appointment. If this still doesn’t do the trick, the bad taste should go away by the end of the day.

6. Increased blood pressure

Nearly 20% of people may experience an increase in blood pressure after receiving Spravato. This could happen any time you receive Spravato, even if you haven’t experienced it in the past.

Your healthcare team will check your blood pressure before and after each Spravato dose. For most people, blood pressure normalizes within 2 to 4 hours of a Spravato dose. But if you experience any serious symptoms when you get home, such as chest pain or shortness of breath, seek emergency medical attention.

Good to know: People with a history of heart problems may be more likely to experience blood pressure problems from Spravato. So make sure to share your complete health history with your prescriber before starting Spravato.

7. Slowed breathing

There have been some reports of serious breathing problems with Spravato. This is extremely rare, but your risk may be higher if you consume other medications or substances that can slow breathing. Giving your prescriber a list of all your medications will help them check for this interaction. And let your prescriber know if you drink alcohol regularly, which can also contribute to slowed breathing (and worsen depression).

The risk of slowed breathing from Spravato is part of the reason you’ll stay at your prescriber’s office for at least 2 hours after receiving your dose. During this time, your healthcare team will monitor your oxygen levels. But let them know right away if at any point you feel like you can’t stay awake or you’re going to pass out.

8. Suicidal thoughts and behaviors

Spravato is approved for people with depression who are having suicidal thoughts or behaviors. But in rare cases, people have experienced worsening depression or thoughts of suicide while receiving Spravato.

This side effect isn’t common. But it’s a good idea to have a plan in place in case it happens. Consider the following tips:

• Arrange for frequent check-ins with your support system (such as family, friends, and healthcare professionals).

• Discuss other treatment options with your prescriber if Spravato hasn’t helped after 4 weeks of treatment.

• Watch for worsening depression and mood changes and seek medical care if they occur.

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the 988 Suicide & Crisis Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.

9. Misuse

Spravato is a controlled substance. This means it has a risk for dependence and misuse. Because of this (and the risk of dissociation and trouble breathing), it’s only given in a healthcare professional’s office.

Both you and your prescriber must enroll in Spravato’s Risk Evaluation and Mitigation Strategy (REMS) program before you can receive it. This is a drug safety program required by the FDA to manage the risks of certain medications. You should only receive Spravato that’s FDA-approved and administered by a healthcare professional.

Spravato misuse is unlikely to be an issue if you’re receiving Spravato as recommended. Misuse is more likely if you’re using non-FDA-approved compounded nasal sprays or if you’re administering Spravato yourself at home. Misuse is also more likely if you have a history of substance use disorder. Your prescriber will discuss the risks and benefits of Spravato with you to make sure it’s a safe option.

If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

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Written by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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