Spravato

What Is Spravato (esketamine)?

Spravato (generic name: esketamine) is the first and only FDA-approved nasal spray used for adults with treatment-resistant depression. Depression is considered “treatment-resistant” when individuals have tried at least two different oral anti-depressant medications and symptoms persist. An estimated 30% of people with major depressive disorder have treatment-resistant depression¹.

In 2019, the U.S. Food & Drug Administration approved Spravato for use alongside an oral antidepressant; in early 2025, the spray was authorized as a standalone treatment. A recent Phase 4 clinical trial¹ found that, four weeks after starting Spravato, 22.5% of participants with major depressive disorder who took the nasal spray alongside an oral antidepressant achieved remission from depression symptoms, compared to 7.6% of participants achieving relief on an oral antidepressant and placebo spray.

It is not known whether SPRAVATO® is safe and effective in children.

How Does Spravato Work?

Spravato works by blocking a receptor in the brain activated by glutamate, a chemical messenger. This mechanism is similar to that found in other antidepressants, which target receptors for chemical messengers like seratonin and dopamine.

What Ingredients Are in Spravato?

The main active ingredient in Spravato is esketamine, which is conventionally used as an anesthetic similar to its parent compound, ketamine. Esketamine is more concentrated than ketamine, requiring a lower dose for efficacy.

Inactive ingredients include citric acid monohydrate, edetate disodium, sodium hydroxide, and water.

How Do You Use Spravato?

The medication is an intranasal spray that is self-administered under the supervision of a healthcare provider at a certified SPRAVATO® treatment center. Patients are required to remain for at least two hours after administration, so healthcare providers can monitor any side effects.

To prevent nausea, it is recommended that patients do not eat at least two hours before receiving the drug and not drink at least 30 minutes before.

What Is the Dosage for Spravato?

The optimal dosage of Spravato varies by patient. The typical dose is 28 mg (two sprays), administered biweekly.

For updated information about dosages, interactions, and precautions, see the Spravato (Esketamine) drug monograph on WebMD.

What Side Effects Are Associated with Spravato?

The most common side effects include:

• Disassociation (feeling disconnected from yourself, thoughts, feelings, and surroundings)
• Dizziness/spinning sensation
• Nausea/vomiting
• Sedation, sleepiness, lack of energy
• Decreased feeling of sensitivity
• Anxiousness
• Increased blood pressure
• Feeling intoxicated
• Headache
• Feeling very excited or happy

Side effects will typically occur 40 minutes after taking the drug and tend to go away within two hours.

Spravato also may have serious side effects, including:

• Allergic reactions: breathing problems, racing heart, fever, stomach cramps
• Memory or thinking problems: unusual changes in judgment/decision-making, trouble concentrating or paying attention, and remembering things
• Bladder problems
• Breathing problems: slow or shallow breathing
• May increase the risk of suicidal thoughts or actions

Consult your healthcare provider about these possible side effects before beginning Spravato.

Visit the Spravato website to see the full list of side effects.

What Precautions Are Associated with Spravato?

You should not take Spravato if you have a history of blood vessel disease or brain bleeding, an abnormal connection between your veins and arteries, or are allergic to esketamine, ketamine, or any other ingredients in Spravato.

Taking Spravato can lead to physical and psychological dependence. If you have a history of drug or alcohol abuse, make sure to discuss it with your doctor before taking Spravato.

This spray has not yet been proven safe and effective for children or for reducing and preventing suicidal thoughts.

Does Spravato Interact with ADHD Stimulants?

Spravato may increase blood pressure and heart rate, a side effect also common with stimulant medications used to treat ADHD, like Adderall and Ritalin. Thus, taking both medications may increase risk of high blood pressure. This is one reason healthcare providers monitor patients’ heart rate and blood pressure in the two hours after medication is administered.

Can You Take Spravato with Another Antidepressant?

According to the label, SPRAVATO® can be used:

• “with or without an antidepressant taken by mouth, to treat adults with treatment-resistant depression”
• “with an antidepressant taken by mouth, to treat depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions.”

What Else Does Spravato Interact With?

When taken with central nervous system depressants, like opioids and benzodiazepines, patients may experience excessive drowsiness and dizziness. The risk of experiencing dizziness and sleepiness may increase with alcohol consumption while taking Spravato.

There are no known interactions between Spravato and foods, herbs, and vitamins. Cannabis use may increase risk of side effects. Patients should discuss these and any other interactions with their healthcare providers.

Limitations of Use

SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe or effective as an anesthetic medicine or if it is safe and effective for use in preventing suicide or in reducing suicidal thoughts or actions.

Spravato Nasal Spray and Other Depression Medications: Next Steps

• Read: Treatments for Depression and ADHD: New and Forthcoming Approaches
• Read: What to Expect When You Start Depression Medication
• Self-Test: Depression in Adults
• Free Download: Understanding Depression in Teens
• Read: How to Treat Depression

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