Esketamine (Spravato)

Brand name: Spravato®

  • Nasal spray: 56 mg dose kit, 84 mg dose kit

Generic name: esketamine (es KET ah meen)

All FDA black box warnings are at the end of this fact sheet. Please review before taking this medication.

What is esketamine and what does it treat?

Esketamine is an intranasal medication that works in the brain. It is approved for the treatment of treatment-resistant depression (TRD) in conjunction with an oral antidepressant.

Symptoms of depression include:

  • Depressed mood — feeling sad, empty, or tearful
  • Feeling worthless, guilty, hopeless, and helpless
  • Loss of interest or pleasure in your usual activities
  • Sleep and eat more or less than usual (for most people it is less)
  • Low energy, trouble concentrating, or thoughts of death (suicidal thinking)
  • Physical aches and pains such as headaches, stomach issue, or muscle pains
  • Psychomotor agitation (‘nervous energy’)
  • Psychomotor retardation (moving and thinking in slow motion)
  • Suicidal thoughts or behaviors

What is the most important information I should know about esketamine?

Do not stop taking esketamine abruptly, even when you feel better. With input from you, your health care provider will assess how long you will need to take the medicine.

Missing doses of esketamine may increase your risk for relapse in your symptoms of depression.

Physical dependence and potential abuse has been reported with prolonged use of ketamine. This can lead to withdrawal signs and symptoms after abrupt discontinuation or a reduction in the drug dose. Likely withdrawal symptoms associated with esketamine include craving, fatigue, poor appetite, and anxiety. Therefore, patients should be monitored for symptoms of dependence after esketamine treatment has ended.

Esketamine can cause excess sedation (sleepiness) in patients after they receive treatment. You will need to remain in the healthcare setting for at least 2 hours (or more) until it is determined by the provider that you are safe to go home. You will need to have a caregiver drive you home.

Because of the risk of serious adverse effects resulting from excessive sedation, esketamine is only available through a restricted program called SPRAVATO REMS. Esketamine can only be administered at healthcare setting certified in the SPRAVATO REMS program and to patients enrolled in the program.

Medical attention should be sought if there is an emergence of worsening depression or suicidal thoughts and/or behaviors. Please notify your healthcare provider right away if you experience this. Refer to Summary of Black Box Warnings.

Are there specific concerns about esketamine and pregnancy?

If you are planning on becoming pregnant, notify your healthcare provider to best manage your medications. People living with TRD who wish to become pregnant face important decisions. Untreated TRD has risks to the fetus, as well as the mother. It is important to discuss the risks and benefits of treatment with your doctor and caregivers.

Esketamine is not recommended during pregnancy. There are insufficient data on the medication use in pregnant women to draw conclusions regarding its safety or risk of birth defects, miscarriage, or other outcomes. There are risks to the mother associated with untreated depression in pregnancy. If a woman becomes pregnant while using esketamine, treatment with this medication should be stopped and the patient should notify the healthcare provider and be counseled on the potential risks to the fetus.

Breast-feeding is not recommended during treatment with esketamine because it passes into human breast milk and can have adverse effects on the child.

What should I discuss with my healthcare provider before taking esketamine?

  • Symptoms of your condition that bother you the most
  • If you have thoughts of suicide or harming yourself
  • Medications you have taken in the past for your condition, whether they were effective or caused any adverse effects
  • If you experience side effects from your medications, discuss them with your provider. Some side effects may pass with time, but others may require changes in the medication.
  • Past or current medical history, especially history of aneurisms, brain hemorrhage, or hypersensitivity to esketamine or ketamine
  • Any other medical problems you have, including high blood pressure as esketamine can further increase blood pressure
  • If you are pregnant, plan to become pregnant, or are breast-feeding
  • If you drink alcohol or use prescription pain killers

How should I take esketamine?

You will take esketamine nasal spray yourself, under the supervision of the healthcare provider, who will instruct you how to use it. The dose and when to take the medication, as well as the treatment schedule may change as the weeks progress.

You will need to remain in the healthcare setting for at least 2 hours after being treated with esketamine until you are safe to leave.

You will need to plan for a caregiver or family member to drive you home after each treatment.

Some people taking esketamine experience nausea and vomiting. You should not eat for at least 2 hours before taking the medication and not drink liquid for at least 30 minutes before taking esketamine.

If you take a nasal corticosteroid or nasal decongestant medicine, take these medicines at least 1 hour before taking esketamine.

What happens if I miss a dose of esketamine?

If you miss a treatment session and there is worsening of depression symptoms, inform your healthcare provider immediately and consider returning to the previous dosing schedule (i.e., every two weeks to once weekly, weekly to twice weekly).

What should I avoid while taking esketamine?

Do not drive, operate machinery, or do anything where you need to be completely alert after taking esketamine nasal spray. Do not take part in these activities until the next day following a restful sleep. Avoid alcohol, illicit substances, or other central nervous system depressants such as sedatives or opioids as they may increase sedation.

What happens if I overdose with esketamine?

If an overdose occurs, call your doctor or 911. You may need urgent medical care. You may also contact the poison control center at 1-800-222-1222.

A specific antidote to reverse the effects of esketamine does not exist.

What are possible side effects of esketamine?

Common side effects

Nausea, diarrhea, vomiting, increased blood pressure, vertigo (spinning sensation), sedation, dizziness, headache, and dissociation (feeling disconnected from mind and body)

Rare/serious side effects

Esketamine can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your healthcare provider will check your blood pressure before taking the dose, and for at least 2 hours following the dose. Tell your healthcare provider right away if you experience chest pain, shortness of breath, sudden severe headache, change in vision, or seizures after taking esketamine.

Other serious side effects include problems with thinking clearly and bladder problems. Tell your healthcare provider if you develop trouble urinating, such as frequent or urgent need to urinate, pain when urinating, or urinating frequently at night.

Are there any risks for taking esketamine for long periods of time?

There is a risk for abuse and dependence with prolonged esketamine treatment. Your healthcare provider should check you for signs of abuse and dependence before and during treatment of esketamine.

What other medications may interact with esketamine?

Esketamine use with monoamine oxidase inhibitors (MAOIs) may increase blood pressure. Closely monitor blood pressure when using esketamine with MAOIs. These include phenelzine (Nardil®), tranylcypromine (Parnate®), isocarboxazid (Marplan®), and selegiline (Emsam®).

Concomitant use of esketamine with stimulants may also increase blood pressure, and should be monitored closely if using together. These include amphetamines (Adderall®), methylphenidate (Ritalin®), modafanil (Provigil®), and armodafanil (Nuvigil®).

Esketamine use with central nervous system (CNS) depressants may increase sedation. Closely monitor for sedation with concomitant use of esketamine with CNS depressants such as benzodiazepines, opioids, and alcohol. These include medications such as alprazolam (Xanax®), diazepam (Valium®), oxycodone (Oxycontin®), and hydromorphone (Dilaudid®) to name a few.

How long does it take for esketamine to work?

Esketamine reaches peak concentrations in the body in between 20 and 40 minutes. It works much more rapidly than traditional antidepressants — in about an hour — and is preferred for use in someone experiencing an acute major depressive episode or even thoughts of self harm.

Summary of FDA Black Box Warnings

Esketamine has the potential to cause sedation and dissociative symptoms. If you experience either of these symptoms, you will need to be observed by a healthcare provider for at least 2 hours at each treatment session, or longer if the symptoms have not resolved. Esketamine, a Schedule III controlled substance may be subject to abuse and dependence. All patients being treated with esketamine should be evaluated before and during treatment for signs and symptoms of abuse or misuse of the mediation. Because of the risks of serious adverse outcomes from sedation, dissociation, and abuse potential, esketamine is only available through a restricted REMS (Risk Evaluation and Mitigation Strategy) program and can only be dispensed in a healthcare setting.

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Adults with major depressive disorder (MDD) may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, especially early during treatment and when the dosage is adjusted. In short-term studies, esketamine showed an increased risk of suicidal thoughts and behaviors in patients 24 years and younger when compared to placebo. It is unknown whether the risk of suicidal thoughts and behaviors expends to long term use i.e., beyond four months. Patients, their families, and caregivers should be alert to the emergence of anxiety, restlessness, irritability, aggressiveness and insomnia. If these symptoms emerge, they should be reported to the patient’s prescriber or healthcare professional. All patients being treated with esketamine should watch for and notify their healthcare provider for worsening symptoms, suicidality and unusual changes in behavior, especially during the first few months of treatment.


Provided by

(February 2020)

©2019 The College of Psychiatric and Neurologic Pharmacists (CPNP). CPNP makes this document available under the Creative Commons Attribution-No Derivatives 4.0 International License. Last Updated: January 2016.

This information is being provided as a community outreach effort of the College of Psychiatric and Neurologic Pharmacists. This information is for educational and informational purposes only and is not medical advice. This information contains a summary of important points and is not an exhaustive review of information about the medication. Always seek the advice of a physician or other qualified medical professional with any questions you may have regarding medications or medical conditions. Never delay seeking professional medical advice or disregard medical professional advice as a result of any information provided herein. The College of Psychiatric and Neurologic Pharmacists disclaims any and all liability alleged as a result of the information provided herein.