SPRAVATO® is the only FDA-approved nasal spray for adults with treatment-resistant depression. It reduces depression symptoms when two or more oral antidepressants haven't worked. SPRAVATO® can be taken with or without an oral antidepressant.

ORAL ANTIDEPRESSANTS MAY NOT WORK FOR EVERYONE

SPRAVATO® offers a different approach.

• SPRAVATO® reduces depression symptoms when oral antidepressants haven't worked

• SPRAVATO® works differently by acting on glutamate — a chemical messenger in the brain thought to help balance well-being and depression

• The exact way SPRAVATO® works is unknown

If you've taken 2 or more oral antidepressants and still experience symptoms of depression, you may have treatment-resistant depression.

• 1 in 3 people did not experience a reduction in their depression symptoms when taking oral antidepressants alone

• Based on a clinical study, 86% of patients do not achieve remission from depression symptoms by their third oral antidepressant

WHAT IS SPRAVATO®?

SPRAVATO® is a prescription medicine used:

• With or without an antidepressant taken by mouth, to treat adults with treatment-resistant depression (TRD)

• With an antidepressant taken by mouth, to treat depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions

SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe and effective in children.

IS THERE PROOF THAT SPRAVATO® CAN HELP?

Short-Term Study Results

Alone: Patients were given either SPRAVATO® alone or a placebo nasal spray alone in a randomized clinical study. The study showed rapid and superior reduction in depression symptoms at approximately 4 weeks and 24 hours for patients using SPRAVATO® alone compared with those who received a placebo nasal spray alone.

In Combination with an Oral Antidepressant: In a 4-week clinical study, patients were given either SPRAVATO® in combination with an oral antidepressant or a placebo nasal spray plus an oral antidepressant. The study showed:

• Rapid and superior reduction in depression symptoms at 4 weeks for more patients using SPRAVATO® in combination with an oral antidepressant compared with those who received placebo plus an oral antidepressant*

• Most of the reduction in depression symptoms was seen at 24 hours

• Continued improvement between 24 hours and 4 weeks for both groups

Long-Term Study Results (18-Month Study)

• Patients who stayed on SPRAVATO® were less likely to experience a return of depressive symptoms (relapse) compared to patients who stopped therapy

• The trial compared patients who stayed on SPRAVATO® and an oral antidepressant to patients on a placebo spray and oral antidepressant long term

*Based on an overall score on a standardized rating scale.

CAN SPRAVATO® HELP WITH MDSI?

In clinical studies of adults with MDD with suicidal thoughts or actions (MDSI), those who took SPRAVATO® and an oral antidepressant experienced a greater reduction of depression symptoms at 24 hours compared with those who received a placebo plus an oral antidepressant.*

Limitations of Use: It is not known if SPRAVATO® is safe and effective for use in preventing suicide or in reducing suicidal thoughts or actions. SPRAVATO® is not for use in place of hospitalization if your healthcare provider determines that hospitalization is needed, even if improvement is experienced after the first dose of SPRAVATO®.

If you're struggling with suicidal thoughts, help is available 24/7. Call 988 Suicide & Crisis Lifeline.

POSSIBLE SIDE EFFECTS OF SPRAVATO®

SPRAVATO® may cause serious side effects, including sleepiness (sedation), fainting, dizziness, spinning sensation, anxiety, feeling disconnected from yourself (dissociation), and breathing problems (respiratory depression and respiratory arrest).

Most Common Side Effects:

• Feeling disconnected from yourself, your thoughts, feelings, and things around you

• Dizziness

• Nausea

• Feeling sleepy

• Spinning sensation

• Decreased feeling of sensitivity (numbness)

• Feeling anxious

• Lack of energy

• Increased blood pressure

• Vomiting

• Feeling drunk

• Headache

• Feeling very happy or excited

If these common side effects occur, they usually happen right after taking SPRAVATO® and go away the same day. In clinical studies, patients on SPRAVATO® experienced a low incidence of sexual dysfunction compared with placebo.

WHERE DO I RECEIVE SPRAVATO®?

SPRAVATO® is administered under the supervision of a healthcare provider at a treatment center certified in the SPRAVATO® Risk Evaluation and Mitigation Strategy (REMS) Program. This could be at a different location than your usual healthcare provider's office.

To locate certified SPRAVATO® treatment centers, visit: SPRAVATO.com/locator

TREATMENT PLAN

Step 1: Treatment Plan

Your healthcare provider will work with you to determine if SPRAVATO® should be taken with or without an oral antidepressant. You may start treatment as soon as your second visit to the SPRAVATO® treatment center.

Your First Visit to a Treatment Center

Your first visit will be a consultation. The treatment center will:

• Receive your medical information from your healthcare provider

• Conduct its own assessment to confirm SPRAVATO® is an appropriate option

• Verify your insurance information as part of the eligibility confirmation

Step 2: Treatment Days

You will administer SPRAVATO® nasal spray yourself under the supervision of a healthcare provider at a certified treatment center. After you administer SPRAVATO®, there will be an observation period of at least 2 hours, during which a healthcare provider will monitor you for possible side effects.

Because of possible side effects affecting mental alertness and motor coordination, you won't be able to drive, operate machinery, or do anything where you need to be completely alert until the next day, following a restful sleep. You'll need to plan for rides on treatment days.

Tips to Prepare for Treatment Days:

• Avoid eating 2 hours before, and drinking liquids 30 minutes before, the treatment session

• If you take a nasal corticosteroid or nasal decongestant medicine, take these at least 1 hour before taking SPRAVATO®

• Many people spend the observation time relaxing, listening to music, reading, or resting

Step 3: Ongoing Treatment

SPRAVATO® Timeline:

• Weeks 1–4 (Induction Phase): Two times per week

• Weeks 5–8 (Optimization Phase): Once per week

• Ongoing (Maintenance Phase): Once per week or every 2 weeks

Dosing strength is based on clinical judgment. In a long-term clinical study, patients who stayed on SPRAVATO® were less likely to relapse.

SUPPORT: SPRAVATO withMe

Once you and your healthcare provider have decided SPRAVATO® is right for you, sign up for SPRAVATO withMe — the support program designed with you in mind.

Sign Up Over the Phone: 1-844-4S-WITHME (1-844-479-4846) Monday – Friday, 8:00 am – 8:00 pm ET

SPRAVATO withMe offers:

• Cost Support

• Dedicated Care Navigator

• Treatment Prep & Ongoing Support

• Free Patient Starter Kit

Cost Savings Programs (Commercial/Private Insurance):

SPRAVATO withMe Savings Program Pay as little as $10 per treatment for your SPRAVATO® medication. Treatment may include up to three devices administered on the same day. There are quantity limits and a maximum program benefit per calendar year. Offer subject to change or end without notice. Program does not cover the cost of treatment observation. See program requirements at: Spravato.com/SavingsRequirements

SPRAVATO withMe Observation Rebate Program Pay $0 after rebate for observation of each treatment. There is a limit to savings each year. Not valid for residents of MA, MI, MN, or RI. See program requirements at: Spravato.com/Observation

If insurance doesn't cover all of your costs, or if you have no insurance, SPRAVATO withMe can provide information about other cost support options.

For more information: SPRAVATO.com/patientsupport

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about SPRAVATO®?

SPRAVATO® can cause serious side effects, including:

1. Sedation, Dissociation, and Respiratory Depression SPRAVATO® may cause sleepiness (sedation), fainting, dizziness, spinning sensation, anxiety, or feeling disconnected from yourself, your thoughts, feelings, space and time (dissociation), and breathing problems (respiratory depression and respiratory arrest).

• Tell your healthcare provider right away if you feel like you cannot stay awake or feel like you are going to pass out.

• Your healthcare provider must monitor you for serious side effects for at least 2 hours after taking SPRAVATO®. Your healthcare provider will decide when you are ready to leave the healthcare setting.

2. Abuse and Misuse There is a risk for abuse and misuse with SPRAVATO®, which may lead to physical and psychological dependence. Your healthcare provider should check you for signs of abuse, misuse, and dependence before and during treatment.

• Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.

3. SPRAVATO® REMS Program Because of the risks for sedation, dissociation, respiratory depression, and abuse and misuse, SPRAVATO® is only available through a restricted program called the SPRAVATO® Risk Evaluation and Mitigation Strategy (REMS) Program. SPRAVATO® can only be administered at healthcare settings certified in the SPRAVATO® REMS Program.
   
   
   

4. Increased Risk of Suicidal Thoughts and Actions Antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. SPRAVATO® is not for use in children.
   
   
   

Tell your healthcare provider or get emergency help right away if you or a family member have any of the following symptoms, especially if they are new, worse, or worry you:

• Thoughts about suicide or dying

• Suicide attempts

• New or worse depression

• New or worse anxiety

• New or worse irritability

• Feeling very agitated or restless

• Panic attacks

• Acting on dangerous impulses

• Trouble sleeping (insomnia)

• An extreme increase in activity and talking (mania)

• Acting aggressive, being angry or violent

• Other unusual changes in behavior or mood

Do Not Take SPRAVATO® If You:

• Have blood vessel (aneurysmal vascular) disease (including in the brain, chest, abdominal aorta, arms and legs)

• Have an abnormal connection between your veins and arteries (arteriovenous malformation)

• Have a history of bleeding in the brain

• Are allergic to esketamine, ketamine, or any of the other ingredients in SPRAVATO®

Before Taking SPRAVATO®, Tell Your Healthcare Provider If You:

• Have heart or brain problems, including high blood pressure, slow or fast heartbeats, history of heart attack, history of stroke, heart valve disease or heart failure, or history of brain injury or increased pressure in the brain

• Have liver problems

• Have ever had a condition called "psychosis"

• Are pregnant or plan to become pregnant — SPRAVATO® may harm your unborn baby (Pregnancy registry: 1-844-405-6185 or womensmentalhealth.org)

• Are breastfeeding or plan to breastfeed — SPRAVATO® passes into breast milk

Tell your healthcare provider about all medicines you take, especially central nervous system (CNS) depressants, psychostimulants, or monoamine oxidase inhibitors (MAOIs).

Additional Side Effects to Know:

• Increased Blood Pressure: SPRAVATO® can cause a temporary increase in blood pressure lasting about 4 hours after a dose. Tell your healthcare provider right away if you get chest pain, shortness of breath, sudden severe headache, change in vision, or seizures.

• Problems with Thinking Clearly: Tell your healthcare provider if you have problems thinking or remembering.

• 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.

These are not all the possible side effects of SPRAVATO®. Call your doctor for medical advice about side effects. You may report side effects to Johnson & Johnson at 1-800-526-7736 or to the FDA at 1-800-FDA-1088.

Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide for SPRAVATO® and discuss any questions you may have with your healthcare provider.

© Johnson & Johnson and its affiliates 2025