Spravato is a brand-name prescription medication that's prescribed for treatment-resistant depression (TRD). TRD is depression that hasn't improved after treatment with two or more antidepressants.

Spravato contains the drug esketamine. It's approved for use in adults, but not in children.

Spravato comes as a nasal spray. It's taken under the supervision of a healthcare provider at a certified medical facility. Spravato should be used in combination with at least one other antidepressant medication that's taken by mouth.

In a clinical study lasting four weeks, Spravato improved symptoms of depression in people taking the drug. One group was given Spravato and an oral antidepressant. The other group was given a placebo (no treatment) and an oral antidepressant. Depression symptoms were measured on a scale of zero to 60 (with higher scores meaning worse depression symptoms).

People taking Spravato had fewer depression symptoms than people taking the placebo. Scores for people taking Spravato improved by 4 points more than scores for people taking the placebo. The greatest improvement in symptoms was seen in the first 24 hours after people took Spravato.

FDA approval

Spravato was approved by the Food and Drug Administration (FDA) in March 2019.

Its approval is considered controversial by some people for a few reasons:

  • Similarity to ketamine. Spravato is similar to ketamine (an anesthetic drug), which is sometimes used as a party drug. However, Spravato and ketamine aren't the same drug. They have some similar effects in the body, but they are different drugs.
  • Fast action. During clinical studies, Spravato lessened depression symptoms within hours after it was taken. This is unlike many other depression medications, which can take weeks to start working.
  • Side effects. Possible side effects of Spravato include dissociation (feeling "out of body") and sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery). Sometimes, these side effects can become severe. Because of this, the FDA requires that Spravato be given by specially trained healthcare providers at certified medical facilities. People who take Spravato are monitored at the facility for at least two hours after they take the drug.
  • Potential for misuse. Spravato has the potential to be misused. This risk is greater in people who have a history of drug misuse or unhealthy drug use.

Long-term studies are still being done regarding how safe and effective Spravato is. The results of these studies will be helpful for doctors managing TRD.

Is Spravato a controlled substance?

Yes, Spravato is a controlled substance. It's classified by the FDA as a schedule three (III) drug. This means that Spravato is accepted for medical use, but has a high risk of dependence. Spravato has the potential to be misused.

The U.S. government passed laws to govern how controlled substances are prescribed and dispensed. Your doctor or pharmacist can tell you more about these laws.

Spravato is available only as a brand-name medication. It's not currently available in generic form.

Spravato contains the drug esketamine.

Spravato is approved by the Food and Drug Administration (FDA) to treat a form of depression called treatment-resistant depression (TRD). It's approved for use in adults, in combination with at least one other antidepressant drug that's taken by mouth.

TRD is a type of depression that hasn't improved after you've tried at least two different antidepressant medications. Your doctor will determine if you have TRD based on your use of other antidepressants.

The Food and Drug Administration (FDA) approves prescription drugs such as Spravato to treat certain conditions. Spravato may also be used off-label for other conditions. Off-label use is when a drug that's approved to treat one condition is used to treat a different condition.

Spravato for treatment-resistant depression

Spravato is FDA-approved to treat a form of depression called treatment-resistant depression (see "Spravato for depression" above). It's approved for use in adults, in combination with at least one other antidepressant that's taken by mouth.

In a clinical study lasting four weeks, Spravato improved symptoms of depression in people taking the drug. One group was given Spravato and an oral antidepressant. The other group was given a placebo (no treatment) and an oral antidepressant. Depression symptoms were measured on a scale of zero to 60 (with higher scores indicating worse depression symptoms).

People taking Spravato had fewer depression symptoms than people taking the placebo. Scores for people taking Spravato improved by 4 points more than scores for people taking the placebo. The greatest improvement in symptoms was seen in the first 24 hours after people took Spravato.

After the four-week trial, some people enrolled in a year-long study. These were people who had a significant improvement in their depression symptoms during the first study.

In the year-long study, Spravato also improved depression symptoms. During this study, people were taking an oral antidepressant with either Spravato or a placebo nasal spray. Those who took Spravato were 51% to 70% less likely to relapse back to severe depression than those taking the placebo.

Spravato for other conditions

You may wonder if Spravato is used to treat other mental health conditions. Spravato hasn't been FDA-approved to treat the conditions described below.

Spravato for anxiety (not an appropriate use)

Spravato isn't approved to treat anxiety. Clinical studies haven't looked at the use of Spravato for this purpose, but studies may take place in the future.

However, ketamine (a drug similar to Spravato) has been studied for use in treating anxiety disorders. These disorders include social anxiety disorder, anxiety in adolescents, and refractory anxiety. Some of these studies have shown promising results, but it's not known if similar results would be seen with Spravato.

More research is needed to know whether Spravato or ketamine are safe or effective for treating anxiety.

Spravato for OCD (not an appropriate use)

Spravato isn't approved to treat obsessive-compulsive disorder (OCD). No clinical studies have been done that would show whether Spravato is effective for treating OCD.

Ketamine (a drug similar to Spravato) has been looked at in several clinical studies as a treatment for OCD. Results in these studies were conflicting. It's not known whether similar results would be seen with Spravato as a treatment for OCD.

More studies are needed to know whether Spravato or ketamine are safe or effective for OCD treatment.

Spravato can cause mild or serious side effects. The following list contains some of the key side effects that may occur while taking Spravato. This list does not include all possible side effects.

For more information on the possible side effects of Spravato, or tips on how to deal with a troubling side effect, talk with your doctor or pharmacist.

More common side effects

The more common side effects of Spravato can include:

  • anxiety
  • dissociation (feeling "out of body")
  • dizziness
  • feeling drunk
  • increased blood pressure
  • lethargy (extreme tiredness)
  • nausea
  • numbness, often in your hands and feet
  • sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery)
  • vertigo (feeling like you're moving when you're not)
  • vomiting

Most of these side effects may go away within a few hours to a couple days. If they're more severe or don't go away, talk to your doctor or pharmacist.

Serious side effects

Serious side effects from Spravato aren't common, but they can occur. Call your doctor right away if you have serious side effects after leaving the doctor's office. Call 911 if your symptoms feel life-threatening or if you think you're having a medical emergency.

Serious side effects and their symptoms can include the following:

  • Severely high blood pressure that can lead to serious events such as seizures, stroke, or hypertensive encephalopathy (swelling inside your brain). Symptoms of high blood pressure can include:
    • chest pain
    • trouble breathing
    • severe headache
    • vision problems (such as blurry vision, or seeing double)
  • Cognitive impairment. Symptoms can include:
    • trouble thinking
    • memory problems
  • Dissociation. Symptoms include:
    • feeling out of body
    • hallucinations (hearing or seeing things that aren't real)
    • strange sensations in some body parts
  • Urinary tract and bladder problems. Symptoms can include:
    • frequent urination (during the day and at night)
    • pain during urination
    • feeling an urgency to urinate
  • Suicidal thoughts and behaviors (in young adults, ages 25 years and younger*). Symptoms can include:
    • worsening of depression
    • sudden thoughts of suicide
    • talking about suicide
    • attempting suicide

* These effects can also occur in children. This drug is not approved for use in children.

Suicide prevention

  • If you know someone at immediate risk of self-harm, suicide, or hurting another person:
  • Call 911 or the local emergency number.
  • Stay with the person until professional help arrives.
  • Remove any weapons, medications, or other potentially harmful objects.
  • Listen to the person without judgment.
  • If you or someone you know is having thoughts of suicide, a prevention hotline can help. The National Suicide Prevention Lifeline is available 24 hours a day at 1-800-273-8255.

Side effect details

You may wonder how often certain side effects occur with this drug, or whether certain side effects pertain to it. Here's some detail on certain side effects this drug may cause.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Spravato. It's not known how often this occurs in people taking Spravato. Symptoms of a mild allergic reaction can include:

  • skin rash
  • itchiness
  • flushing (warmth and redness in your skin)

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

  • angioedema (swelling under your skin, typically in your eyelids, lips, hands, or feet)
  • swelling of your tongue, mouth, or throat
  • trouble breathing

You will stay in the doctor's office for at least two hours after you take Spravato. Your healthcare provider will monitor you for side effects or allergic reactions.

Call your doctor right away if you have a severe allergic reaction to Spravato after leaving the office. Call 911 if your symptoms feel life-threatening or if you think you're having a medical emergency.

Dissociation

Dissociation was one of the most common side effects seen during clinical trials of Spravato. This condition is a change in your mental state. It's often described as having an "out-of-body" experience. People can feel disconnected from time, space, or their own body or mind.

Symptoms of dissociation can include:

  • vision changes, such as double vision and blurry vision
  • feeling cold or hot
  • hallucinations (hearing or seeing things that aren't real)
  • numbness
  • strange sensations in some body parts
  • ringing in your ears
  • feeling time pass more slowly or more quickly than normal

In clinical trials of Spravato, between 61% and 75% of people taking the drug had symptoms of dissociation. These symptoms, which were temporary, occurred on the day Spravato was taken. Dissociation was more common in people ages 65 years and older. It was also more common in people taking higher doses than in people taking lower doses of the drug.

In clinical studies, only 0.4% of people stopped taking Spravato because of dissociation symptoms.

During your appointment to receive Spravato, your healthcare provider will monitor you for at least two hours after you take the drug. They will check you for side effects including dissociation. They'll let you know when it's safe for you to go home.

Some people have a greater risk of dissociation after taking Spravato. If you have a history of psychosis, you may be at increased risk. Talk with your doctor about whether Spravato is safe for you.

Sedation

Sedation was a common side effect seen in clinical studies of Spravato. Symptoms of sedation include extreme sleepiness, having trouble thinking, and a decreased ability to respond.

In clinical studies, sedation was more common in:

  • People taking higher doses. Sedation occurred less often in people taking lower doses of the drug.
  • People who were younger. Sedation occurred in up to 61% of people younger than age 65 years, and in 49% of people ages 65 and older.

Only 0.3% of people actually lost consciousness after taking Spravato in the studies. This means there was a short period where they didn't respond when their healthcare provider tried to wake them.

Some medications taken with Spravato can also cause symptoms of sedation. People using these medications may be at increased risk of sedation.

After taking Spravato, you'll stay in the healthcare facility for at least two hours. Your doctor will monitor you for symptoms of sedation. They will advise when you can safely go home. You'll need a trusted friend or family member to drive you home. You shouldn't drive or operate heavy machinery until after you've had a full night's sleep.

Increases in blood pressure

Increased blood pressure was seen in people taking Spravato during clinical studies. Up to 17% of people who took Spravato had increased blood pressure. The blood pressure changes seen within 1.5 hours of taking Spravato included:

  • more than 40 mmHg increase in systolic blood pressure (the top number of your blood pressure)
  • more than 25 mmHg increase in diastolic blood pressure (the bottom number of your blood pressure)

Your doctor will check your blood pressure before you take Spravato. If your blood pressure is high, they may recommend that you wait to take your dose of Spravato. You and your doctor can weigh the benefits and risks of using this drug at that time.

Your doctor will also check your blood pressure about 40 minutes after you take Spravato. They will have you stay at the healthcare facility at least two hours after taking Spravato. If your blood pressure is high after you take the drug, you may need to stay at the facility longer for monitoring or possible treatment.

If you have uncontrolled high blood pressure before starting Spravato, your doctor may decide that you shouldn't use this drug. (For more information, see "Spravato warnings" below.)

The Spravato dosage your doctor prescribes will depend on how your body responds to Spravato.

Typically, your doctor will start you on a low dosage and adjust it over time to reach the dosage that's right for you. They'll ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. Your doctor will determine the best dosage to suit your needs.

Drug forms and strengths

Spravato comes as a nasal spray. It's given through a special device that sprays the drug into your nose. Each device delivers two sprays of the medication. Each spray contains 14 mg of Spravato.

Depending on the dose your doctor prescribes, you will need to use either two or three devices each time you take Spravato.

Dosage for depression

The dosage for Spravato is given in two phases: An induction (starting) phase and a maintenance (ongoing) phase.

Each dose of Spravato is taken under the supervision of your healthcare provider at a certified medical clinic. Your blood pressure will be checked before you take the drug, and you'll be monitored for side effects for at least two hours after you take Spravato.

Induction phase (weeks 1 through 4)

The induction phase lasts for the first four weeks of Spravato treatment. During this phase, you'll take the drug two times each week.

The first dose of Spravato is 56 mg. Each dose after that is either 56 mg or 84 mg. Your doctor will prescribe your dose based on how well your body tolerates the drug.

At the end of the induction phase, you and your doctor will discuss whether you should continue to the maintenance phase. This decision depends on how well the drug works for you and if you're tolerating any side effects.

Maintenance phase (week 5 and after)

The maintenance phase starts at the beginning of week 5 of using Spravato. During week 5 through week 8, you'll take Spravato once each week.

During week 9 and after, you'll take Spravato either once weekly or twice weekly.

The dose during the maintenance phase is either 56 mg or 84 mg. Your doctor will advise how often you should use Spravato. This depends on how well your body tolerates the medication and if your symptoms improve. Ultimately, your doctor will prescribe the lowest dose that's effective for you.

What if I miss a dose?

If you miss an appointment for a Spravato dose, call your doctor's office as soon as you remember. They will reschedule your appointment. They may also adjust your upcoming appointments to better fit your schedule. This helps you maintain a safe and effective dosing schedule.

Will I need to use this drug long term?

It depends. Your doctor may recommend that you take Spravato on a long-term basis if it's safe, effective, and necessary for you. You and your doctor will make this decision together.

As with all medications, the cost of Spravato can vary. Your doctor's office will purchase Spravato from a specialty pharmacy. Spravato isn't available for you to purchase at a pharmacy.

Spravato may be covered by your prescription insurance coverage or your medical insurance coverage. This will depend on your specific insurance plan.

Financial and insurance assistance

If you need financial support to pay for Spravato, or if you need help understanding your insurance coverage, help is available.

Janssen, the manufacturer of Spravato, offers a program called Janssen CarePath. For more information and to find out if you're eligible for support, call 844-777-2828 or visit the program website.

Spravato is taken as a nasal spray that you'll administer yourself. You will take the drug at a certified medical facility. Your doctor will show you how to use the nasal spray device. They'll also monitor you while you take Spravato to make sure you don't have any problems using the device.

Before your dose

You will be asked to blow your nose before you take the first spray of Spravato. This is done to make sure the medication is not blocked by any congestion inside your nose.

Your healthcare provider will provide the correct number of devices needed for your treatment. The number of devices you'll use depends on your specific dose. Each nasal spray device contains 28 mg of Spravato. If your dose is 56 mg, you'll need to use two devices. If your dose is 84 mg, you'll use three Spravato devices.

Your doctor will show you how to use the nasal spray device. Before you take the dose, you'll recline to about a 45-degree angle. This helps the medication stay inside your nose so that your body can absorb it.

During and after your dose

Your healthcare provider will monitor you while you're taking Spravato. They'll continue to watch you for at least two hours after your dose. This monitoring is done to make sure that you have no serious side effects after your treatment. Your doctor will advise when you can safely leave the clinic.

You'll need to have someone drive you home after your Spravato treatment. You shouldn't drive after taking the drug. You should also avoid taking part in activities that require coordination and mental alertness. You can usually resume all of your normal activities the day after your Spravato treatment.

When to take

Spravato is taken once or twice per week. Your doctor will recommend the dosing schedule that's best for you.

Taking Spravato with food

Spravato may cause nausea or vomiting in some people. To help prevent these side effects:

  • don't eat food for at least two hours before your treatment
  • don't drink any liquids for at least 30 minutes before your treatment

Depression is a complicated mood disorder. It's thought to be caused in part by imbalanced levels of neurotransmitters in your brain. Neurotransmitters are chemical messengers in your body that help nerves communicate with each other. Examples of neurotransmitters include serotonin and dopamine.

Neurotransmitter levels can become imbalanced if they increase or decrease in activity. This can affect the body's ability to function properly. Moods and mental well-being can be affected by imbalance in neurotransmitter levels. These imbalances may also be related to depression.

It's not known exactly how Spravato helps improve depression symptoms. It may be related to how Spravato interacts with neurotransmitters.

Spravato blocks a neurotransmitter called glutamate from binding to a certain receptor (attachment site) on your nerves. The blocked receptor is called NMDA (N-methyl-D-aspartate) receptor. Blocking glutamate from attaching to this receptor may help regulate communication between nerve cells in the brain. This may help improve symptoms of depression.

How long does it take to work?

Spravato starts working very quickly. In clinical studies, many people who took Spravato felt improved depression symptoms within four hours of taking the drug.

Other drugs are available that can treat your condition. Some may be better suited for you than others. If you're interested in finding an alternative to Spravato, talk to your doctor to learn more about other medications that may work well for you.

Note: Some of the drugs listed here are used off-label to treat this condition.

Alternatives for treatment-resistant depression

Depression is a very complicated disease that we're still learning about. Because of its complexity, treating depression is often a process of trial and error. You may need to try several different medications before you find one that helps improve your symptoms.

There are many different medications available to treat depression. The following are examples of other drugs that may be used for depression, including treatment-resistant depression (TRD):

  • serotonin norepinephrine reuptake inhibitors (SNRIs), including:
    • desvenlafaxine (Khedezla, Pristiq)
    • duloxetine (Cymbalta)
    • venlafaxine (Effexor XR)
  • selective serotonin reuptake inhibitors (SSRIs), including:
    • citalopram (Celexa)
    • escitalopram (Lexapro)
    • fluoxetine (Prozac)
    • paroxetine (Paxil, Paxil CR)
    • sertraline (Zoloft)
  • dopamine norepinephrine reuptake inhibitors, including:
    • bupropion (Alpenzin, Forfivo XL, Wellbutrin SR, Wellbutrin XL)
  • norepinephrine-serotonin modulators, including:
    • mirtazapine (Remeron)
  • tricyclic antidepressants, including:
    • amitriptyline
    • desipramine (Norpramin)
    • nortriptyline (Pamelor)
  • antipsychotics, including:
    • aripiprazole (Abilify, Abilify Maintena, Aristada)
    • olanzapine (Zyprexa, Zyprexa Relprevv)
    • quetiapine (Seroquel, Seroquel XR)
  • other medications, such as:
    • lithium (Lithobid)
    • levothyroxine (Synthroid, Unithroid)

Spravato is approved for use in combination with other antidepressant medications. It should always be used with at least one other antidepressant that's taken by mouth.

There are many different antidepressant medications that can be used with Spravato. Many of the treatment options listed above in "Alternatives to Spravato" can also be taken with Spravato.

You may wonder how Spravato compares to other medications that are prescribed to treat treatment-resistant depression (TRD). Below are comparisons between Spravato and other medications.

Spravato vs. Abilify

Spravato contains the drug esketamine. Abilify contains the drug aripiprazole. These medications belong to different drug classes, but they're both used to treat depression.

Uses

Spravato is approved to treat a form of depression called treatment-resistant depression (TRD) in adults. It's approved for use in combination with at least one other antidepressant medication that's taken by mouth.

Abilify is approved to treat depression in adults. It should also be used in combination with other antidepressant medications. It's also approved to treat the following conditions:

  • schizophrenia
  • manic or mixed episodes of bipolar I disorder
  • irritability related to autism
  • Tourette's syndrome
  • agitation related to schizophrenia or bipolar mania

Drug forms and administration

Spravato comes as a nasal spray. It's given either once or twice each week. It's usually given in doses of 56 mg or 84 mg.

You'll give Spravato to yourself at a certified healthcare facility. Healthcare providers will monitor you for side effects during and after your treatment. You'll stay at the facility for at least two hours after you receive your dose. Your doctor will let you know when it's safe for you to go home.

Abilify comes in these forms:

  • tablets (taken by mouth)
  • orally disintegrating tablets (dissolve inside your mouth)
  • liquid solution (taken by mouth)
  • injection

There is also an Abilify oral tablet available that has a sensor inside. This sensor can track when you take your medication.

Abilify is usually taken once per day by mouth when used to treat depression. The usual dosage range in adults is 2 mg to 15 mg. This drug can be taken at home. It doesn't need to be given at a certified healthcare facility.

Side effects and risks

Spravato and Abilify contain very different drugs. Therefore, these medications can cause different side effects. Below are examples of these side effects.

More common side effects

These lists contain examples of more common side effects that can occur with Spravato, with Abilify, or with both drugs (when taken individually).

  • Can occur with Spravato:
    • dissociation
    • sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery)
    • vertigo
    • numbness or strange sensations in your skin
    • lethargy (extreme tiredness)
    • increased blood pressure
    • feeling drunk
  • Can occur with Abilify:
    • constipation
    • headache
    • blurred vision
    • upper respiratory infections
    • insomnia (trouble sleeping)
    • feeling restless
    • weight gain
  • Can occur with both Spravato and Abilify:
    • nausea
    • vomiting
    • dizziness
    • anxiety

Serious side effects

These lists contain examples of serious side effects that can occur with Spravato, with Abilify, or with both drugs (when taken individually).

  • Can occur with Spravato:
    • high blood pressure, leading to serious events, including heart attack or stroke
    • sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery)
  • Can occur with Abilify:
    • stroke in people ages 56 or older
    • neuroleptic malignant syndrome (an adverse reaction to antipsychotics, similar to serotonin syndrome)
    • tardive dyskinesia (uncontrolled movement of body parts)
    • changes in metabolism that can cause high blood sugar, diabetes, and weight gain
    • unusual urges (such as gambling or binge eating)
    • orthostatic hypotension (low blood pressure when you stand up)
    • low white blood cell count (neutropenia)
    • seizures
    • trouble regulating body temperature
    • trouble swallowing, which may lead to food or liquid entering your lungs
  • Can occur with both Spravato and Abilify:
    • suicidal thoughts or behavior, especially in young adults

Effectiveness

Spravato and Abilify have different FDA-approved uses, but they're both used to treat types of depression. They're given in combination with other antidepressant medications.

The use of Spravato and Abilify haven't been directly compared in clinical studies. Studies have found that both Spravato and Abilify are effective for treating certain types of depression.

Costs

Spravato and Abilify are both brand-name drugs. There aren't any generic forms of Spravato available. Abilify tablets and solutions are available in generic forms. Brand-name drugs usually cost more than generics.

According to estimates on GoodRx.com, Spravato may cost more than brand-name and generic forms of Abilify. The actual price you would pay for either drug depends on your dose, your insurance plan, your location, and the pharmacy you use.

Spravato vs. Symbyax

Spravato contains the drug esketamine. Symbyax contains two drugs: olanzapine and fluoxetine. These medications belong to different drug classes, but they're both used to treat depression.

Uses

Both Spravato and Symbyax are FDA-approved to treat a form of depression called treatment-resistant depression (TRD). Spravato is approved for use in adults, in combination with at least one other antidepressant drug. Symbyax is approved for use alone in adults with TRD.

Symbyax is also approved for acute depressive episodes caused by bipolar I disorder in adults and in children ages 10 years and older.

Drug forms and administration

Spravato comes as a nasal spray. It's given either once or twice each week. It's usually given in doses of 56 mg or 84 mg.

Spravato is self-administered in a certified healthcare facility. Healthcare providers will monitor you for side effects during and after your treatment. You'll stay at the facility for at least two hours after your dose. Your doctor will advise when it's safe for you to go home.

Symbyax comes as a capsule that's taken by mouth. It's taken once daily, in the evening. This drug doesn't need to be taken at a certified healthcare facility.

Symbyax capsules come in several different strengths:

  • 3 mg olanzapine/25 mg fluoxetine
  • 6 mg olanzapine/25 mg fluoxetine
  • 6 mg olanzapine/50 mg fluoxetine
  • 12 mg olanzapine/25 mg fluoxetine
  • 12 mg olanzapine/50 mg fluoxetine

Side effects and risks

Spravato and Symbyax contain very different medications. Therefore, they can cause different side effects. Below are examples of these side effects.

More common side effects

These lists contain examples of more common side effects that can occur with Spravato, with Symbyax, or with both drugs (when taken individually).

  • Can occur with Spravato:
    • dissociation
    • vertigo
    • numbness or strange sensations in your skin
    • lethargy (extreme tiredness)
    • increased blood pressure
    • feeling drunk
    • nausea
    • vomiting
    • dizziness
    • anxiety
  • Can occur with Symbyax:
    • weight gain
    • increased appetite
    • dry mouth
    • fatigue (low energy levels)
    • edema (swelling) in your feet, ankles, and legs
    • tremor (shaking, usually in your hands and arms)
    • blurry vision
    • trouble paying attention
  • Can occur with both Spravato and Symbyax:
    • sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery)

Serious side effects

These lists contain examples of serious side effects that can occur with Spravato, with Symbyax, or with both drugs (when taken individually).

  • Can occur with Spravato:
    • increased blood pressure, leading to serious events, including heart attack or stroke
  • Can occur with Symbyax:
    • neuroleptic malignant syndrome (adverse reaction to antipsychotics, similar to serotonin syndrome)
    • serotonin syndrome
    • tardive dyskinesia (uncontrolled movement of body parts)
    • changes in metabolism that cause high blood sugar, diabetes, and weight gain
    • life-threatening rash, called drug reaction with eosinophilia and systemic symptoms (DRESS)
    • angle-closure glaucoma
    • activation of mania or hypomania
    • orthostatic hypotension (low blood pressure when you stand up)
    • low white blood cell count (neutropenia)
    • seizures
    • bleeding easily or bleeding more often than usual
    • abnormal heart rhythm
    • high levels of prolactin (a certain hormone in your body)
    • increased risk of death in people ages 65 years and older with psychosis
  • Can occur with both Spravato and Symbyax:
    • trouble thinking clearly
    • suicidal thoughts or behavior, especially in young adults

Effectiveness

Spravato and Symbyax have different FDA-approved uses, but they're both used to treat treatment-resistant depression (TRD).

These drugs haven't been directly compared to each other in clinical studies. However, both Spravato and Symbyax have been effective to treat depression symptoms during clinical studies.

Costs

Spravato and Symbyax are both brand-name drugs. There aren't any generic forms of Spravato available. However, there is a generic form of Symbyax available. Brand-name medications usually cost more than generics.

According to estimates from GoodRx.com, Spravato may cost more than Symbyax. The actual price you would pay for either drug depends on your dose, your insurance plan, your location, and the pharmacy you use.

Spravato shouldn't be taken with alcohol. Both Spravato and alcohol can cause sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery). Taking them together can increase this risk.

Spravato can interact with several other medications. It can also interact with certain supplements as well as certain foods.

Different interactions can cause different effects. For instance, some can interfere with how well a drug works, while others can cause increased side effects.

Spravato and other medications

Below are lists of medications that can interact with Spravato. These lists do not contain all the drugs that may interact with Spravato.

Before taking Spravato, be sure to tell your doctor and pharmacist about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Spravato and opioids

Spravato and opioids can both cause sedation. Taking Spravato together with opioid drugs can cause excessive sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery).

If you're taking an opioid pain medication and need Spravato treatment, talk to your doctor about your risk of sedation. You may need to be monitored for a longer time after taking Spravato to make sure that you don't feel sedated after treatment.

Examples of opioids that can increase the risk of sedation if taken with Spravato include:

  • hydrocodone (Hysingla, Zohydro)
  • oxycodone (Oxycontin, Roxicodone, Xtampza ER)
  • codeine
  • morphine (Kadian, MS Contin)
  • fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Subsys)

Many pain relievers contain a combination of drugs, and one of those drugs may be an opioid. Be sure to tell your doctor about all medications you take. If you're taking an opioid, they may recommend a different medication for you. This can help you avoid an increased risk of sedation.

Spravato and benzodiazepines

Spravato and benzodiazepines can both cause sedation. Taking Spravato and benzodiazepines together can cause excessive sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery).

If you're taking a benzodiazepine and considering Spravato treatment, talk with your doctor about the risk of sedation. You may need to be monitored for a longer time after taking Spravato to make sure that you don't feel sedated after treatment.

Examples of benzodiazepines that can increase sedation if taken with Spravato include:

  • alprazolam (Xanax, Xanax XR)
  • diazepam (Valium)
  • lorazepam (Ativan)
  • temazepam (Restoril)
  • triazolam (Halcion)

Spravato and sleep medication

Taking Spravato with medications that are used to help you fall or stay asleep can cause prolonged or worsened sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery).

Talk to your doctor if you take medications to help you sleep. They may recommend that you skip your sleep medication on the night before your Spravato dose.

If you take medications to help you sleep, you may need to be monitored for a longer time after taking Spravato. This will help make sure that you are not sedated after your treatment.

Examples of sleep medication that can increase sedation if taken with Spravato include:

  • eszopiclone (Lunesta)
  • zaleplon (Sonata)
  • zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist)

Spravato and stimulant medications

Taking Spravato with stimulant medications may increase blood pressure more than either drug would alone. Increased blood pressure could cause serious complications with blood vessels in your heart or brain. These complications include heart attack, stroke, or swelling in your brain.

Examples of stimulant medications include:

  • amphetamines/amphetamine salts (Adderall XR, Dexedrine, Dyanavel XR, Evekeo, Mydayis, Vyvanse)
  • methylphenidate (Adhansia XR, Aptensio XR, Concerta, Daytrana, Focalin, many others)
  • modafinil (Provigil)
  • armodafinil (Nuvigil)

If you are taking a stimulant medication, talk to your doctor about your risk of elevated blood pressure. You may need to be monitored more closely after taking Spravato for dangerously high blood pressure.

Spravato and monoamine oxidase inhibitors

Taking Spravato with monoamine oxidase inhibitors (MAOIs) can cause an increase in blood pressure. Increased blood pressure could cause serious complications with blood vessels in your heart or brain. These complications include heart attack, stroke, or swelling in your brain.

MAOIs are a class of medications used to treat depression. Examples of MAOIs that can cause high blood pressure if taken with Spravato include:

  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • selegiline (Emsam, Zelapar)
  • tranylcypromine (Parnate)

If you are taking an MAOI, talk to your doctor about your risk of elevated blood pressure. They may monitor you more closely for dangerously high blood pressure after your Spravato treatments.

Nasal corticosteroids or nasal decongestants

Taking a nasal corticosteroid or nasal decongestant around the time of your Spravato dose may reduce how much Spravato your body absorbs. This could make the drug less effective for you.

To avoid this interaction, don't use a nasal corticosteroid or nasal decongestant for at least one hour before your Spravato dose.

Spravato and foods

Eating or drinking certain things around the time of your Spravato dose may increase your risk of side effects.

Food and drink on the day of Spravato dose

Spravato can cause nausea and vomiting in some people. To reduce this risk:

  • don't eat food for at least two hours before taking Spravato, and
  • don't drink liquids for at least 30 minutes before taking Spravato

Spravato and caffeine

Caffeine, which is a stimulant, can increase your blood pressure. Spravato may also increase blood pressure. Taking Spravato with caffeine could increase your blood pressure to levels that are not safe.

If you consume caffeine, talk with your doctor about how much is safe for you to consume on the day of your Spravato dose.

Spravato is not recommended for use during pregnancy. In animal studies, pregnant females who received Spravato had offspring with brain and bone damage. However, it's not known how Spravato use during pregnancy would affect humans.

If you are pregnant or may become pregnant, talk with your doctor about the safety of Spravato use during pregnancy.

If you take Spravato during pregnancy, you are encouraged to contact the National Pregnancy Registry for Antidepressants. This registry collects information about the safety of antidepressant use during pregnancy. You can register by calling 844-405-6185 or visiting the NPRAD website.

Breastfeeding is not recommended for women who are taking Spravato.

It's not known for sure how Spravato would affect humans who consume it in breast milk. However, it is known that the drug passes into human breast milk. In animal studies, Spravato passed into the breastmilk of lactating mothers and caused brain damage when this milk was consumed by animals.

If you're breastfeeding and considering Spravato treatment, your doctor may recommend that you stop breastfeeding while you receive treatment.

Here are answers to some frequently asked questions about Spravato.

Why is this drug controversial?

Spravato is considered controversial by some people for two main reasons:

  • it's made from a drug called ketamine
  • it can cause severe side effects

The active drug in Spravato is called esketamine, which is made from ketamine. Ketamine is approved by the Food and Drug Administration (FDA) for use as an anesthetic. However, it's also taken as a "party drug" that's referred to as "Special K" and can be misused.

It's important to note that Spravato and ketamine are not the same drug (see the next section, "What's the difference between esketamine and ketamine?"). Both drugs are only available with a prescription from a healthcare provider. However, Spravato is only given at certified healthcare facilities and can't be purchased for use at home.

As for the second concern about Spravato, it can cause serious side effects, including sedation (sleepiness, trouble thinking clearly, or inability to drive or use heavy machinery) and dissociation (an "out-of-body" experience). Because Spravato has these serious side effects, the FDA has placed restrictions on its use. It can only be given through a Risk Evaluation and Mitigation Strategy (REMS) (see the section below, "What is a REMS?") at certified medical facilities.

The REMS requires that after taking Spravato, you'll be monitored by a healthcare provider for at least two hours. During this time, they'll watch you for side effects. They'll also make sure it's safe for you to leave the facility.

You shouldn't drive at all on the day of your Spravato treatment. You'll need to have someone who can drive you home after your treatment. You'll be able to resume driving the day following your treatment.

What's the difference between esketamine and ketamine?

Esketamine (the active drug in Spravato) and ketamine are not the same drug, but they are similar chemicals. Esketamine is found in ketamine. It's what's called an enantiomer.

Ketamine contains a mixture of enantiomers, which are two chemicals that are mirror images of each other. Enantiomers look similar to each other but have different effects inside the body. Esketamine is one of these mirror images found within ketamine. Esketamine is made when it's removed from ketamine.

It's thought that ketamine and esketamine work differently because of their different structures. These drugs interact in different ways with nerves in your brain.

Spravato is approved to treat a form of depression called treatment-resistant depression (TRD). It's used in combination with other antidepressant medications taken by mouth.

Ketamine isn't approved to treat depression at this time. However, it is approved for use as an anesthetic drug during surgeries or other medical procedures.

Several small studies have looked at using ketamine to treat depression. These studies have had promising short-term results. Up to 71% of people who took ketamine had improved depression symptoms. However, more studies are needed to know if ketamine is safe and effective for long-term treatment of depression.

What is a REMS?

A REMS (Risk Evaluation and Mitigation Strategy) is a program created by the Food and Drug Administration (FDA). It's used to reduce the risks related to prescribing certain drugs.

The FDA requires that some prescription drugs be given through REMS programs. This typically includes drugs that have serious side effects.

REMS programs help educate consumers on how to safely use certain medications. REMS programs also teach healthcare providers how to prescribe certain drugs. This helps doctors know if the drug's benefit outweighs its risk when used for medical treatment.

The REMS program for Spravato requires that healthcare facilities that give Spravato be certified to administer the drug. Spravato isn't available for purchase at your local pharmacy. You can only receive the drug at certified healthcare facilities.

The REMS program also requires that you're fully informed of the risks before taking Spravato. Risks can include serious side effects such as sedation (sleepiness, trouble thinking clearly, or inability to drive or use heavy machinery) and dissociation (an "out-of-body" experience).

If you're taking Spravato, you'll need to sign an enrollment form stating that you understand the following:

  • You'll need to stay for at least two hours to be monitored for sedation and dissociation at the healthcare facility before you can leave and go home.
  • You'll have someone else with you to safely drive you home after treatment.
  • You won't drive or use heavy machinery until the day after your treatment.

Additional information about the REMS requirements for Spravato can be found on the FDA's website.

Is esketamine also used as an anesthetic?

No, it's not. The active drug in Spravato (esketamine) isn't approved for use as an anesthetic for surgery. Ketamine (a drug similar to esketamine) is FDA-approved to be used as an anesthetic.

Does Spravato cause hallucinations?

Yes, Spravato can cause hallucinations in some people. This side effect is most likely to occur within minutes to hours after taking Spravato.

You'll stay at your doctor's office for at least two hours after you take Spravato. This allows the healthcare provider to monitor you for any side effects, including hallucinations. Your healthcare provider will let you know when they feel you can safely go home.

This drug comes with several warnings.

FDA warnings

This drug has boxed warnings. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

  • Sedation. Spravato can cause sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery). This can make certain activities, such as driving, unsafe. You'll take Spravato at a licensed healthcare facility. After you take Spravato, you'll be monitored for at least two hours before you leave the facility and go home.
  • Dissociation. Spravato can cause temporary dissociation. Dissociation is a change in your mental state. It can make you feel disconnected from time, space, and your own body or mind. Your healthcare provider will monitor you for this side effect for at least two hours after you take Spravato.
  • Misuse. Spravato can be misused. For this reason, it's prescribed by specially trained healthcare providers, and it's given to people only at certified healthcare facilities. Spravato may not be right for people with a history of substance misuse.
  • Suicidal thoughts and behaviors. Like other antidepressants, Spravato may increase the risk of suicidal thoughts or behaviors in children and young adults (ages 25 years and younger). Spravato is not approved for use in children.

Other precautions

Before taking Spravato, talk with your doctor about your health history. Spravato may not be right for you if you have certain medical conditions. These include:

  • Aneurysmal vascular disease or arteriovenous malformation. Spravato can increase blood pressure in the first few hours after taking the drug. There is risk for serious bleeding events after taking Spravato. This risk is greater in people with a history of aneurysms and people who have malformations of their arteries. Spravato shouldn't be used in people with these risk factors.
  • History of intracerebral hemorrhage. Spravato can increase your blood pressure. Increased blood pressure can increase the risk of bleeding inside your brain. Spravato should not be used by people with a history of bleeding in the brain.
  • History of psychosis. Spravato may cause dissociation (an "out-of-body" experience). People with a history of psychosis may be at greater risk for a severe dissociative or psychotic event. If you have a history of psychosis or psychotic events, talk with your doctor about whether Spravato is right for you.
  • History of substance use disorder. Spravato is a controlled substance that may be misused. Talk with your doctor about any history of substance use disorder, addiction, or misuse. Your doctor can help you decide if Spravato is right for you.
  • Hypertension (high blood pressure). Spravato can increase blood pressure. This puts increased strain on your heart, blood vessels, and brain. If you have high blood pressure, talk with your doctor about whether Spravato is safe for you.
  • Liver disease. People with liver disease may be at greater risk of side effects from Spravato. They may also be at risk for a longer period of time after taking the drug. If you have moderate liver disease, your doctor may monitor you in the healthcare facility for longer than the standard time.

Note: For more information about the potential negative effects of Spravato, see the "Spravato side effects" section above.

The following information is provided for clinicians and other healthcare professionals.

Indications

Spravato (esketamine) is FDA-approved to treat treatment-resistant depression in combination with oral antidepressant therapy. It is only approved for use in adults.

Mechanism of action

Spravato is the S-enantiomer of ketamine. It is a nonselective, noncompetitive antagonist of the NMDA receptor. It works by blocking glutamate activity. The exact mechanism of action for treating depression is unknown.

Pharmacokinetics and metabolism

Esketamine exposure is dose-proportional between 56 mg and 84 mg. There is no evidence of accumulation from twice weekly dosing.

Absolute bioavailability is approximately 48% following nasal administration. Maximum concentration is reached within 20 to 40 minutes after the dose. Decline in concentration is biphasic; levels rapidly decline in the first 2 to 4 hours, but have a terminal half-life of 7 to 12 hours.

Protein binding is 43% to 45%. Metabolism occurs via CYP2B6, CYP3A4, CYP2C9, and CYP2C19. Elimination of metabolites occurs primarily in urine, and to a lesser degree in feces.

Contraindications

Spravato is contraindicated in patients with a history of hypersensitivity to esketamine, ketamine, or any of Spravato's excipients.

Spravato is also contraindicated in people with aneurysmal vascular disease, arteriovenous malformation, or history of intracerebral hemorrhage.

Misuse and dependence

Spravato is classified by the DEA as a Schedule III controlled substance, indicating a potential for misuse and dependence.

Storage

Spravato should be stored at room temperature (68°F to 77°F/20°C to 25°C). Used devices should be disposed of per applicable schedule three (III) drug laws.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.