9 Spravato Side Effects to Know About

Depression can be a difficult experience. And if you or a loved one have tried multiple medications without relief, it’s even harder. In some cases, your medical care team may recommend something more than oral antidepressants alone.

Recently, ketamine infusions have been in the spotlight as a depression treatment option. But at this time, injectable ketamine isn’t FDA-approved for this use. Spravato (esketamine) is a ketamine-like medication that’s available as a nasal spray. It's the only FDA-approved ketamine-based treatment for severe or treatment-resistant depression, and it has to be given by a healthcare professional. Even though it’s been called a game-changer, there’s still some important Spravato side effects to consider. 

Spravato side effects at a glance

Spravato was approved by the FDA in 2019. In initial clinical trials, as well as more recent studies of people receiving Spravato in the real world, recipients reported similar side effects. 

Common/mild side effects include:

• Sleepiness

• Nausea and vomiting

• Dissociation (feeling detached from reality)

• Dizziness

• Headache

• 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 side effects include:

• High blood pressure

• Slowed breathing

• Suicidal thoughts and behaviors

• Hallucinations

• Loss of consciousness

• Dependence and misuse

In this article, we’ll talk more in-depth about nine of these Spravato side effects.

Good to know: You shouldn’t receive Spravato if you’re 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. 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

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 if you take other medications that make you sleepy, drowsiness can worsen. Your healthcare provider may ask you to avoid sedating medications while you’re being treated with Spravato. Examples include benzodiazepines, opioids, and sleeping pills. 

Plan on resting after you get home from your Spravato treatment. If you live alone, ask a friend or family member to check in on you. And if you still feel tired a day or two later, let your prescriber know.

Good to know: Spravato is typically prescribed along with oral antidepressants, many of which are known to cause drowsiness. So if tiredness from other medications is affecting your daily life, let your healthcare team know.

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. 

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 provider 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 less common but also possible. To lower the risk, stop eating at least 2 hours before (and drinking at least 30 minutes before) your Spravato dose.

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 your own flavored water or powdered drink mix packets to add to water, so you can drink something after your Spravato dose. If this doesn’t work, know that your mouth will likely feel normal by the end of the day.

6. Increased blood pressure

Up to 20% of people may experience an increase in blood pressure after receiving Spravato. This could happen with any Spravato dose, 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 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 immediate medical attention.

Keep in mind: 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 take other medications or use substances (such as alcohol) that can slow breathing. Giving your prescriber a list of all your medications will help them check for interactions. And let your prescriber know if you drink alcohol, 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 oxygen levels will be monitored. Your medical team will let you know when it’s safe to go home. But let them know right away if 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 provider if Spravato hasn’t helped after 4 weeks of treatment.

• Be watchful for worsening depression and mood changes

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. And 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. 

Spravato misuse is unlikely to be an issue if you’re receiving Spravato as recommended under your healthcare team’s supervision. Misuse is more likely if you’re using non-FDA-approved compounded nasal sprays or if you’re administering Spravato yourself at home. You should only receive Spravato that’s FDA-approved and administered by a healthcare professional. Misuse is also more likely if you have a history of substance use disorder.

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.

When should you seek medical care for Spravato side effects?

Most Spravato side effects go away within 2 hours of receiving your dose. And since you’ll be in your prescriber’s office during that time, you can alert your care team about any side effects.

But if you experience any Spravato side effects that continue into the following day, let your healthcare team know. And if you notice any of the following severe symptoms, seek emergency care:

• Severe mood changes

• Chest pain

• Trouble breathing

• Hallucinations

• Suicidal thoughts or actions

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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:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed 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.

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