What You Need To Know About Spravato (Esketamine)

What is Spravato? What is it used for? How does it work? Is Spravato for you? How is it given? Where is it given? What are the problems that can occur if you take this medication? Can you become addicted to Spravato? Read on to get some answers.

One of the patients who participated in the Spravato study had this to say: “It was hard to have any emotions because I was just numb. When I began treatment with esketamine and my symptoms started to lift, I could see very clearly just how depressed I had been. I’m now able to appreciate a wider range of emotions than when I was depressed. My long-term goals have taken shape and actually seem attainable.”

Spravato is a new medication approved in 2019 for treatment-resistant depression. It is used together with other depression medications given by mouth. Spravato is unique in the sense that it is available as a nasal spray. It also has a different way of acting as compared to other medications used to treat depression. This medication helps depressed people who have tried other depression medications without relief.


When is Spravato used?

There are different classes of medications used to treat depression. It is likely you have tried a few remedies for your depression. Most of these medications act on specific parts of the brain. These actions lead to the release of brain chemicals like serotonin, norepinephrine, and dopamine.

Spravato acts on a different part of the brain and helps with depression by a different mechanism of action. This medication presents a new way of treating depression. Spravato is only used in adults. It is not for use in children.

This new medication is used for treatment-resistant depression (TRD) in adults only. The active ingredient in this medication is esketamine. This is similar to but different from ketamine. Unlike ketamine, Spravato is not used as an anesthetic.

Spravato is not a first-line drug. It is only prescribed if you have tried and failed at least 2 medications for depression. Even when prescribed Spravato, you have to take other antidepressants.


Treatment-Resistant Depression

Depression is a mental illness that affects over 400 million people worldwide. Depression causes low mood, poor sleep, decreased appetite, poor concentration, feelings of hopeless and worthless, low energy levels and suicidal thoughts.

There are several medications that help with depression. About 33% of people who have depression may not respond to these medications. When at least two different antidepressants have been tried in an adequate dose and time, with no response, this is known as treatment-resistant depression (TRD).

Treatment-resistant depression may cause you to struggle with your life. This can also affect your loved ones and society as a whole. Your depression may cause difficulty in managing life’s demands and also maintaining social connections. It can affect school, work, relationships and quality of life.


What makes this medication special?

spravatoSpravato has a different way of working in the brain to help with depression. This is the first time in several decades that a medication which works differently has been made. It is given as a nasal spray instead of taken by mouth.

Several studies showed that people who were given both Spravato and a depression medication taken by mouth showed better improvement in their depression. The improvements also lasted much longer.

This nasal spray relieves depressive symptoms within hours to days. Much faster than other medications used to treat depression. Antidepressants like Zoloft can take weeks to act.

Spravato is only given in special treatment centers. It is not for use at home. Certified treatment centers have staff trained to give you this medication. In such centers, you administer Spravato yourself, but under supervision.


The first major advance in decades!

Prozac is a depression medication that revolutionized depression treatment. It was approved in 1988. There has been very little in terms of different acting medications since then. Until now. The Food and Drug Administration approved Spravato in March 2019. It is the first new type of depression treatment in over three decades. Spravato is a major advance in depression treatment.

Gerard Sanacora, M.D. is the director of the Yale Depression Research Program. In his words, “It’s quite possibly the biggest advance for mental health in the past 50 years.

This medication seems to be effective where other depression medications like Zoloft, Wellbutrin and Effexor have failed. It also acts really quickly.

Spravato is a new way of treating depression. It is a nasal spray unlike other medications taken by mouth. Most antidepressants increase serotonin, norepinephrine, and dopamine in the brain. These brain chemicals then act on glutamate. Esketamine works directly on glutamate. This is why it works so rapidly.


Is Esketamine different from Ketamine?

Vox had this to say: “The Food and Drug Administration just approved a big pharma variant on the hallucinogenic club drug Special K for the treatment of depression.”

Spravato contains esketamine. This is like ketamine, a substance used as an anesthetic. Ketamine is also used off-label to treat resistant depression. These centers are commonly called “Ketamine clinics.” Esketamine is the s-enantiomer of ketamine.

Janssen developed esketamine, sold as Spravato. According to the FDA, this is the first time esketamine has been approved for any use. The agency approved ketamine, a related drug, in 1970. Also known as “Special K,” ketamine is a party drug and was made a controlled substance in 1999.


Side effects and risks

Spravato can cause the following side effects:

  • Drowsiness
  • Nausea
  • Vomiting
  • Reduced sense of touch and sensation
  • Spinning sensation
  • High blood pressure
  • Anxiety
  • Feeling disconnected from yourself, your thoughts, feelings, space and time (dissociation)
  • Worsening depression
  • Suicidal thoughts and behaviors
  • Problem thinking or remembering things
  • Feeling drunk
  • Trouble urinating, pain when urinating, or urinating several times at night

These side effects do not happen to everyone. Most people tolerate Spravato quite well. If side effects occur, they tend to go away the same day.

The blood pressure increase with Spravato is usually temporary. The increased reading may last about 4 hours after taking a dose of Spravato. Blood pressure is checked before the first dose, at 40 minutes and at 2 hours.

Inform your healthcare provider if you have side effects with Spravato. You may also report side effects to the FDA at 1-800-FDA-1088.


Can you become addicted to this nasal spray?

There is a risk for misuse and abuse of Spravato. This medication can cause physical and psychological dependence. It is a Schedule III controlled substance. People with a history of drug abuse or dependence may be at a greater risk for abuse or misuse of Spravato.

Your healthcare provider will check for signs of abuse and dependence before and during treatment with Spravato. You should inform your healthcare provider if you have ever abused ketamine, alcohol, prescription medications, or other street drugs.

Because of the risk of side effects, abuse, and misuse, Spravato is only available through a special program. This is the Spravato Risk Evaluation and Mitigation Strategy (REMS) Program.

Ketamine causes dependence when used in high doses for long periods. Dependence leads to withdrawals when an abused substance is suddenly stopped.

Withdrawal symptoms of ketamine include craving, fatigue, poor appetite, and anxiety. Such symptoms are likely to occur if esketamine is similarly abused. In studies where esketamine was given in prescribed doses, no withdrawal was noticed after it was stopped in 4 weeks.

Tolerance is a decreased response to a drug after it has been taken for some time. This means a higher dose is needed to cause the same effect. Tolerance occurs with ketamine. A similar tolerance is expected with long term use of esketamine at high doses.


Overdosing on Spravato

There is no specific treatment for esketamine overdose. Taking other medications at the same time may make an overdose worse. The Spravato REMS program is designed to minimize misuse and abuse.

If you overdose on Spravato, contact a Certified Poison Control Center. They give the most up to date information for overdoses. You can reach a center by calling 1-800-222-1222. Their website is also another way to contact them – www.poison.org.


Avoid taking Spravato if you have any of these!

You should avoid taking this medication if you have any of the following:

  1. blood vessel disease (aneurysm)
  2. abnormal connection between your veins and arteries (arteriovenous malformation)
  3. history of bleeding in your brain
  4. allergy to esketamine, ketamine, or any of the other ingredients in Spravato

If you are not sure if you have any of the following, talk to your healthcare provider before taking Spravato.


Caution if you have any of these medical conditions

Before taking Spravato, tell your healthcare provider about the following:

  • high blood pressure
  • history of stroke
  • heart valve disease
  • heart failure
  • slow or fast heartbeats that cause shortness of breath, chest pain, lightheadedness, or fainting
  • history of brain injury
  • liver problems
  • history of psychosis (seeing, feeling, or hearing things that are not there, or believing in things that are not true)
  • breastfeeding or plans to breastfeed
  • pregnancy or plans to get pregnant


Interactions with other medications

You should inform your healthcare provider of all the medications you are taking. Some medications may cause side effects with Spravato. Medications which cause interactions are:

      1. Central Nervous System (CNS) depressants(e.g. benzodiazepines, opioids, and alcohol). These can increase drowsiness.
      2. Psychostimulants(e.g. amphetamines, methylphenidate, modafinil, armodafinil). These can cause increased blood pressure.
      3. Monoamine Oxidase Inhibitors (MOAIs). Medications like selegiline, phenelzine, and tranylcypromine can increase blood pressure.

    Also inform your healthcare provider of all your other prescriptions, vitamins, herbal supplements, and over-the-counter medications.


    How is Spravato given?

    1. The first step is to have a consultation with your healthcare provider. You have to be diagnosed with treatment-resistant depression to qualify for esketamine treatment.
    2. Your healthcare provider may be a Certified Treatment Center. You will get a referral to one if that is not the case. You cannot take Spravato home.
    3. In a Certified Treatment Center, you will sign a Patient Enrollment Form. This is to enroll you in the SPRAVATO REMS program.
    4. A benefits investigation is done with your insurance to make sure they will pay. This takes a few days. Self-pay is an option. Note that Spravato is expensive.
    5. On the day of your first treatment, you attend the Certified Treatment Center. You will take Spravato nasal spray yourself supervised by a healthcare provider.
    6. Do not eat for at least 2 hours before taking Spravato. Also, do not drink at least 30 minutes before Spravato treatment.
    7. If you take a decongestant or nasal corticosteroid, take them at least 1 hour before taking Spravato.
    8. Your blood pressure will be checked a few times during each treatment with esketamine.
    9. You are observed for 2 hours before discharge. This is to make sure you have no side effects.
    10. A caregiver, family member or friend has to drive you home after treatment. You are not allowed to drive or operate heavy machinery for 24 hours.
    11. Missed doses of Spravato may cause your healthcare provider to change your dose and treatment schedule.

    You will be enrolled in the SPRAVATO REMS registry to monitor side effects, abuse, misuse and to support the safe use of this medicine.


    What is the recommended dosage for Spravato?

    Dosing for this medication is done in Induction and Maintenance Phases.

    Induction Phase (Weeks 1 -4)
    • Given twice per week
    • Day 1 starting dose is 56 mg
    • After the first dose, 56 mg or 84 mg
    Maintenance Phase (Weeks 5 – 8)
    • Given once weekly
    • 56 mg or 84 mg
    Maintenance Phase (Week 9 and after)
    • Given every 2 weeks or once weekly
    • 56 mg or 84 mg


  1. Each nasal spray contains 28 mg of esketamine contained within 0.2 ml of liquid. Two devices are used for 56 mg. Three devices are used for 84 mg. There is a 5-minute rest between the use of each device. It takes about 20 – 40 minutes for Spravato to reach the highest blood levels.

    How much does Spravato cost?

    Spravato is not cheap. It is covered by some insurance plans and you should check with your insurance. Your healthcare provider can also do a benefits investigation to help with this.

    This medication costs between $4,720 and $6,785 before insurance, discounts, and rebates. This is for the first month. It is cheaper the second month, costing between $2,360 and $3,450. Each dose costs about $500 to $800, depending on the dose. This cost is closer to other depression treatments like Transcranial Magnetic Stimulation (TMS) and Electroconvulsive Therapy (ECT).


    Spravato Risk Evaluation and Mitigation Strategy (REMS)

    Spravato is only available through a restricted program. This is because of the risks for drowsiness, out-of-body experience, and abuse and misuse. This program called Spravato REMS requires the following:

    1. All patients must be in the Spravato REMS program. This is before the first dose
    2. Spravato must be given with supervision from a healthcare provider. This must be in a Certified Treatment Center.
    3. Patients will need monitoring for at least 2 hrs after a dose of Spravato



    Spravato is a new medication used for treatment-resistant depression. It is a nasal spray approved only in adults. It is not used for children. The active ingredient in Spravato is esketamine.

    Ketamine, also known as Special K, is a party drug that can lead to addiction. Abusing esketamine can also cause dependence. Spravato is a Schedule III medication which is very closely monitored.

    Spravato works quickly. It is given together with other depression medications taken by mouth. It is only given in Certified Treatment Centers and cannot be taken home. This is the first medication of its kind approved for depression in several decades. Unlike other antidepressants, it acts on a different chemical in the brain.

    Side effects with this medication include drowsiness, nausea, vomiting, high blood pressure, out-of-body experience, anxiety, feeling drunk and suicidal thoughts. Avoid taking Spravato if you have blood vessel disease, abnormal connection between your veins and arteries, history of brain bleeding or allergy to esketamine or ketamine.

    You should avoid combining Spravato with central nervous system depressants, psychostimulants or monoamine oxidase inhibitors. This medication requires enrollment in the Spravato REMS program. You will be monitored for 2 hours after a dose and you are not allowed to drive until the next day, after a restful night sleep.

    Spravato is initially given twice a week for one month. It is given once a week in the second month. From the third month, it is given once in two weeks or once a week. Spravato is expensive but some insurance plans cover it.

    To locate a Spravato treatment center, you can visit www.SPRAVATO.com.

    Share this information with anyone who may benefit from this medication. Subscribe to our newsletter for future articles related to addiction and mental health.