Can Esketamine Nasal Spray Treat Depression?

Table of ContentsView AllTable of ContentsUsesBefore TakingDosageSide EffectsWarnings and Interactions

Table of ContentsView All

View All

Table of Contents

Uses

Before Taking

Dosage

Side Effects

Warnings and Interactions

What is the most important information I should know about esketamine?You should not use esketamine if you are pregnant, planning to become pregnant, or breastfeeding.Esketamine can cause severe sedation after treatment; it is only administered in healthcare, and you should be monitored for a minimum of two hours after treatment.

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

You should not use esketamine if you are pregnant, planning to become pregnant, or breastfeeding.Esketamine can cause severe sedation after treatment; it is only administered in healthcare, and you should be monitored for a minimum of two hours after treatment.

Esketamine is an NMDA (N-methyl-D-aspartate) receptor antagonist used to treat adults withtreatment-resistant depression(TRD). Esketamine (which is sold under the brand name Spravato) comes as a nasal spray and is said to rapidly reduce suicidal ideations anddepressive symptoms.

Of the 8.9 million adults treated with medications for major depressive disorder each year, approximately 2.8 million (or 30.9%) have treatment-resistant depression.TRD is a term used to describe depression that has failed to respond to at least two different antidepressants.

Esketamine Uses

Esketamine nasal spray is approved for use in adults 18 and over, in conjunction with aselective serotonin reuptake inhibitor(SSRI) orserotonin and norepinephrine reuptake inhibitor(SNRI). To be considered for this treatment, patients must have tried at least two other antidepressants without success.

Most oral antidepressants need weeks or even months to take effect. Clinical trials suggest that esketamine nasal spray can significantly reduce symptoms in as little as 24 hours.

Esketamine vs. KetamineEsketamine is derived fromketamine, a powerful anesthetic. Though both drugs have similar makeup (ketamine is a mixture of two mirror-image molecules, and esketamine is one of those molecules), esketamine is more potent.

Esketamine vs. Ketamine

Esketamine is derived fromketamine, a powerful anesthetic. Though both drugs have similar makeup (ketamine is a mixture of two mirror-image molecules, and esketamine is one of those molecules), esketamine is more potent.

Clinical Drug Trials

Esketamine effectiveness was evaluated in three short-term (four weeks) studies, one maintenance study, and a long-term safety study. Two of these studies demonstrated that esketamine rapidly reduces depressive symptoms in people with TRD.

One was a short-term trial involving adults under age 65 who were started on an oral antidepressant and intranasal esketamine.After one month, roughly 70% of patients (compared to just over half in theplacebo group) who received esketamine saw at least a 50% reduction in depressive symptoms.

The other positive study was the maintenance study which assessed relapse prevention. Data from this trial showed that esketamine reduces relapse rates. Specifically, those treated with esketamine nasal spray plus an oral antidepressant had a 50% to 70% lower risk of relapse than patients who only received an oral antidepressant.

More research is still needed to determine the optimal dosing, assess other possible side effects, and establish the safety of esketamine in the longer term.

Despite decades of research, themolecular mechanisms underlying depressionare poorly understood. Consequently, scientists aren’t exactly certain how esketamine reduces depression. What is clear is that it is fast-acting. Within hours, people may experience changes to the brain that reducesymptoms of depression.

Before Taking Esketamine

Esketamine should never be used as a first-line of treatment. Instead, it is intended for individuals with TRD, meaning they have had adequate trials of two other antidepressant medications first and didn’t experience relief.

Precautions and Contraindications

Esketamine is not appropriate for everyone. You should not take esketamine if you are allergic to esketamine or ketamine, or if you have or have had any of the following medical conditions:

You should also talk to your doctor if you have ever had:

Esketamine may cause fetal harm, and those who are pregnant or considering becoming pregnant should talk to their doctors. People should not breastfeed while undergoing treatment.

Alternative Treatment Options

Esketamine may be an option for individuals who are at an acute risk of suicide. Individuals who are in crisis may need a fast-acting drug that can offer immediate relief.

But esketamine isn’t the only option for individuals with TRD. Other options may include:

Esketamine Dosage

Each device contains 28 milligrams (mg) and delivers two sprays. The recommended dosage for TRD is as follows:

You will need to remain in the healthcare setting for at least two hours after being treated. During this time, your healthcare provider will closely monitor you for adverse reactions. When it is safe for you to leave, you will need someone to drive you home.

Modifications

The safety and efficacy of esketamine have not been established for pediatric use. Guidelines for use among people 65 and older are the same as those for other adults.

How to Know Which Antidepressant Is Best for You

Side Effects of Esketamine

Like any new treatment, manufacturers will continue to monitor any adverse reactions. Johnson & Johnson, who developed esketamine, is taking steps to ensure it will only be used as intended.

Common

In clinical trials, the most common side effects included the following:

Patients should not drive or operate heavy machinery after taking esketamine until the next day after a restful sleep, as it can impair reaction time and motor skills.

Severe

Call your doctor if you experience severe side effects, including:

Get emergency medical help if you have signs of an allergic reaction, including hives, difficulty breathing, or swelling of the face, throat, lips, or tongue.

The esketamine labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.For more mental health resources, see ourNational Helpline Database.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see ourNational Helpline Database.

Drug Interactions

Esketamine can interact with a number of other medications and supplements. These substances may impact the way that your antidepressant works or your antidepressant may influence the effects of those substances.

Drugs that are known to interact with esketamine include:

Using alcohol while taking this drug may also increase the severity of side effects including drowsiness, difficulty thinking, confusion, motor impairment, and dizziness.

In order to minimize the risk of potentially dangerous interactions, you should always tell your doctor about any other prescription medications, over-the-counter drugs, vitamins, herbs, or other supplements you’re currently taking or plan on taking.

Can You Drink Alcohol While You’re on a Medication?

Esketamine also has the potential for misuse and can cause physical dependence. Doctors are advised to balance the possible benefits with the potential risks, particularly for people at higher risk for substance misuse and addiction.

Overview of the Treatments for Depression

7 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.U.S. Food and Drug Administration.Spravato label.Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):29169.Ionescu DF, Fu D-J, Qiu X, et al.Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II).Int J Neuropsychopharmacol. Published online August 29, 2020. doi:10.1093/ijnp/pyaa068Berman RM, Cappiello A, Anand A, et al.Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9Popova V, Daly E, Trivedi M, et al.Randomized, double-blind study of flexibly-dosed intranasal esketamine plus oral antidepressant vs. active control in treatment-resistant depression.Biological Psychology. 2018;83(9):S390. doi:10.1016/j.biopsych.2018.02.1002Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial.JAMA Psychiatry. 2019;76(9):893-903. doi:10.1001/jamapsychiatry.2019.1189Center for Drug Evaluation and Research.FDA briefing document: Psychopharmacologic drugs advisory committee (PDAC) And drug safety and risk management (DSaRM) Advisory committee meeting. U.S. Food and Drug Administration.Additional ReadingAjub E, Lacerda ALT.Efficacy of esketamine in the treatment of depression with psychotic features: A case series.Biol Psychiatry.2018;83(1):e15-e16. doi:10.1016/j.biopsych.2017.06.011Canuso CM, Singh JB, Fedgchin M, et al.Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double-blind, randomized, placebo-controlled study.Am J Psychiatry. 2018;175(7):620-630. doi:10.1176/appi.ajp.2018.17060720Singh JB, Fedgchin M, Daly E, et al.Intravenous esketamine in adult treatment-resistant depression: A double-blind, double-randomization, placebo-controlled study.Biol Psychiatry. 2016;80(6):424-31. doi:10.1016/j.biopsych.2015.10.018Targum SD, Daly E, Fedgchin M, Cooper K, Singh JB.Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression.J Psychiatr Res. 2019;111:68-73. doi:10.1016/j.jpsychires.2019.01.017U.S. Food and Drug Administration. Office of the Commissioner.Press Announcements - FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

7 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.U.S. Food and Drug Administration.Spravato label.Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):29169.Ionescu DF, Fu D-J, Qiu X, et al.Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II).Int J Neuropsychopharmacol. Published online August 29, 2020. doi:10.1093/ijnp/pyaa068Berman RM, Cappiello A, Anand A, et al.Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9Popova V, Daly E, Trivedi M, et al.Randomized, double-blind study of flexibly-dosed intranasal esketamine plus oral antidepressant vs. active control in treatment-resistant depression.Biological Psychology. 2018;83(9):S390. doi:10.1016/j.biopsych.2018.02.1002Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial.JAMA Psychiatry. 2019;76(9):893-903. doi:10.1001/jamapsychiatry.2019.1189Center for Drug Evaluation and Research.FDA briefing document: Psychopharmacologic drugs advisory committee (PDAC) And drug safety and risk management (DSaRM) Advisory committee meeting. U.S. Food and Drug Administration.Additional ReadingAjub E, Lacerda ALT.Efficacy of esketamine in the treatment of depression with psychotic features: A case series.Biol Psychiatry.2018;83(1):e15-e16. doi:10.1016/j.biopsych.2017.06.011Canuso CM, Singh JB, Fedgchin M, et al.Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double-blind, randomized, placebo-controlled study.Am J Psychiatry. 2018;175(7):620-630. doi:10.1176/appi.ajp.2018.17060720Singh JB, Fedgchin M, Daly E, et al.Intravenous esketamine in adult treatment-resistant depression: A double-blind, double-randomization, placebo-controlled study.Biol Psychiatry. 2016;80(6):424-31. doi:10.1016/j.biopsych.2015.10.018Targum SD, Daly E, Fedgchin M, Cooper K, Singh JB.Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression.J Psychiatr Res. 2019;111:68-73. doi:10.1016/j.jpsychires.2019.01.017U.S. Food and Drug Administration. Office of the Commissioner.Press Announcements - FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

U.S. Food and Drug Administration.Spravato label.Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):29169.Ionescu DF, Fu D-J, Qiu X, et al.Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II).Int J Neuropsychopharmacol. Published online August 29, 2020. doi:10.1093/ijnp/pyaa068Berman RM, Cappiello A, Anand A, et al.Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9Popova V, Daly E, Trivedi M, et al.Randomized, double-blind study of flexibly-dosed intranasal esketamine plus oral antidepressant vs. active control in treatment-resistant depression.Biological Psychology. 2018;83(9):S390. doi:10.1016/j.biopsych.2018.02.1002Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial.JAMA Psychiatry. 2019;76(9):893-903. doi:10.1001/jamapsychiatry.2019.1189Center for Drug Evaluation and Research.FDA briefing document: Psychopharmacologic drugs advisory committee (PDAC) And drug safety and risk management (DSaRM) Advisory committee meeting. U.S. Food and Drug Administration.

U.S. Food and Drug Administration.Spravato label.

Zhdanava M, Pilon D, Ghelerter I, et al.The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States.J Clin Psychiatry. 2021;82(2):29169.

Ionescu DF, Fu D-J, Qiu X, et al.Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II).Int J Neuropsychopharmacol. Published online August 29, 2020. doi:10.1093/ijnp/pyaa068

Berman RM, Cappiello A, Anand A, et al.Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9

Popova V, Daly E, Trivedi M, et al.Randomized, double-blind study of flexibly-dosed intranasal esketamine plus oral antidepressant vs. active control in treatment-resistant depression.Biological Psychology. 2018;83(9):S390. doi:10.1016/j.biopsych.2018.02.1002

Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial.JAMA Psychiatry. 2019;76(9):893-903. doi:10.1001/jamapsychiatry.2019.1189

Center for Drug Evaluation and Research.FDA briefing document: Psychopharmacologic drugs advisory committee (PDAC) And drug safety and risk management (DSaRM) Advisory committee meeting. U.S. Food and Drug Administration.

Ajub E, Lacerda ALT.Efficacy of esketamine in the treatment of depression with psychotic features: A case series.Biol Psychiatry.2018;83(1):e15-e16. doi:10.1016/j.biopsych.2017.06.011Canuso CM, Singh JB, Fedgchin M, et al.Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double-blind, randomized, placebo-controlled study.Am J Psychiatry. 2018;175(7):620-630. doi:10.1176/appi.ajp.2018.17060720Singh JB, Fedgchin M, Daly E, et al.Intravenous esketamine in adult treatment-resistant depression: A double-blind, double-randomization, placebo-controlled study.Biol Psychiatry. 2016;80(6):424-31. doi:10.1016/j.biopsych.2015.10.018Targum SD, Daly E, Fedgchin M, Cooper K, Singh JB.Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression.J Psychiatr Res. 2019;111:68-73. doi:10.1016/j.jpsychires.2019.01.017U.S. Food and Drug Administration. Office of the Commissioner.Press Announcements - FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

Ajub E, Lacerda ALT.Efficacy of esketamine in the treatment of depression with psychotic features: A case series.Biol Psychiatry.2018;83(1):e15-e16. doi:10.1016/j.biopsych.2017.06.011

Canuso CM, Singh JB, Fedgchin M, et al.Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double-blind, randomized, placebo-controlled study.Am J Psychiatry. 2018;175(7):620-630. doi:10.1176/appi.ajp.2018.17060720

Singh JB, Fedgchin M, Daly E, et al.Intravenous esketamine in adult treatment-resistant depression: A double-blind, double-randomization, placebo-controlled study.Biol Psychiatry. 2016;80(6):424-31. doi:10.1016/j.biopsych.2015.10.018

Targum SD, Daly E, Fedgchin M, Cooper K, Singh JB.Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression.J Psychiatr Res. 2019;111:68-73. doi:10.1016/j.jpsychires.2019.01.017

U.S. Food and Drug Administration. Office of the Commissioner.Press Announcements - FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

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

Esketamine Uses#

Esketamine vs. Ketamine#

Clinical Drug Trials#

Before Taking Esketamine#

Precautions and Contraindications#

Alternative Treatment Options#

Esketamine Dosage#

Modifications#

Side Effects of Esketamine#

Common#

Severe#

Drug Interactions#