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Esketamine nasal spray

Updated 2 Feb 2023 | Other antidepressants


Nasal spray containing esketamine.

Drugs List

  • esketamine 28mg/0.2ml nasal spray
  • SPRAVATO 28mg/0.2ml nasal spray
  • Therapeutic Indications


    Major depressive episodes in patients with MDD: adjunctive treatment

    Treatment of adults with treatment-resistant major depressive disorder, in combination with an SSRI or SNRI, who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.


    Treatment is recommended for at least 6 months once depressive symptoms improve.

    It is recommended to maintain the dose the patient receives at the end of the induction phase in the maintenance phase. Dose adjustments should be made based on efficacy and tolerability to the previous dose. During the maintenance phase, esketamine dosing should be individualised to the lowest frequency to maintain remission/response.


    Weeks 1 to 4
    Induction phase: 56mg on day one.
    Increasing thereafter to 56mg or 84mg twice a week.
    The therapeutic benefit should be evaluated at the end of the induction phase to determine the need for continual treatment.

    Weeks 5 to 8
    Maintenance dose: 56mg or 84mg once a week.

    Week 9 onwards
    56mg or 84mg every 2 weeks or once a week.

    Patients of Japanese ancestry
    Weeks 1 to 4
    Induction phase: 28mg on day one.
    Increasing thereafter to 28mg, 56mg or 84mg twice a week in 28mg increments.
    The therapeutic benefit should be evaluated at the end of the induction phase to determine the need for continual treatment.

    Weeks 5 to 8
    Maintenance dose: 28mg, 56mg or 84mg once a week, changes in 28mg increments.

    Week 9 onwards
    28mg, 56mg or 84mg every 2 weeks or once a week, changes in 28mg increments.


    Patients aged 65 and over

    Weeks 1 to 4
    Induction phase: 28mg on day one.
    Increasing thereafter in increments of 28mg to 28mg, 56mg or 84mg twice a week.
    The therapeutic benefit should be evaluated at the end of the induction phase to determine the need for continual treatment.

    Weeks 5 to 8
    Maintenance dose: 28mg, 56mg or 84mg once a week, changing in 28mg increments.

    Week 9 onwards
    28mg, 56mg or 84mg every 2 weeks or once a week, changing in 28mg increments.

    Patients with Hepatic Impairment

    Moderate hepatic impairment: Maximum dose 84mg.

    Additional Dosage Information

    Missed dose
    If one or two treatment sessions are missed, the following treatment should be scheduled when the next session was scheduled, based on current frequency. If more than two treatments are missed, the dose or frequency of treatment may be altered as per clinical judgement.


    Do not re-administer if sneezing occurs immediately after administration. If administration occurs in the same nostril, do not administer a replacement device.


    Children under 18 years
    Arterial aneurysm
    History of cerebrovascular haemorrhage
    Recent myocardial infarction
    Renal dialysis
    Severe hepatic impairment

    Precautions and Warnings

    Females of childbearing potential
    Suicidal ideation
    Bipolar disorder
    Cardiovascular disorder
    Cerebrovascular disorder
    History of bipolar disorder
    History of drug misuse
    History of mania
    History of psychosis
    Moderate hepatic impairment
    Raised intracranial pressure
    Respiratory disease
    Uncontrolled hyperthyroidism

    Patients at risk of suicide should be closely supervised
    Advise patient ability to drive or operate machinery may be impaired
    Advise patient not to drive until they know how the medicine affects them
    Advise patient this medicine may be subject to driving restrictions
    Consider reduced dose in patients of East Asian ancestry
    Treatment should be initiated by a psychiatrist
    Advise patient to avoid drinking 30 minutes before administration
    Advise patient to avoid nasal preparations within 1 hour before treatment
    Avoid solid food for at least 2 hours prior to administration
    Patient should be closely observed, if possible within an inpatient setting
    Treatment to be administered under the supervision of a specialist
    Monitor blood pressure pre-treatment and periodically thereafter
    Discontinue treatment immediately if pregnancy is suspected
    Monitor for signs of suicide ideation or behaviour
    Monitor for urinary tract and bladder symptoms
    Reassess need for continued treatment at regular intervals
    Reduce dose in elderly
    Advise patient to avoid alcohol during treatment
    Advise that effects are potentiated by CNS depressants (including alcohol)
    Advise patient/carers to report signs of suicide ideation or behaviour

    Patients with clinically significant or unstable cardiovascular or respiratory conditions should have treatment administered where resuscitation equipment and trained professionals in cardiopulmonary resuscitation are available.

    Where an increase in blood pressure or intracranial pressure would put the patient at risk, it should be determined whether the potential benefits of treatment outweighs the risks. Treatment should not be started if an increase in intracranial pressure or blood pressure poses a serious risk. Treatment may also be delayed if blood pressure is elevated due to lifestyle or pharmacological therapies.

    Blood pressure should be measured 40 minutes after treatment and regularly thereafter as clinically appropriate. Any treatment sessions with esketamine can cause transient increases in systolic and/or diastolic blood pressure which peaks at approximately 40 minutes and can last 1 to 2 hours. If blood pressure remains elevated for a prolonged period of time, assistance should be sought from practitioners specialised in blood pressure management. Patients experiencing symptoms of a hypertensive crisis should be immediately referred to emergency care.

    Prior to treatment the patient should be assessed for the risk of abuse or misuse.

    Elderly patients have an increased risk of falls and should be monitored.

    Chronic ketamine use has been associated with hepatotoxicity, therefore such an effect cannot be excluded during long term esketamine treatment.

    Patients requiring a nasal corticosteroid or nasal decongestant on the day of dosing should not administer the medicinal product 1 hour before treatment administration.

    Due to the possibility of sedation, dissociation and elevated blood pressure, patients must be monitored by a healthcare professional until the patient is considered clinically stable and ready to leave the healthcare setting.

    Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

    Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

    Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

    Pregnancy and Lactation


    Esketamine is contraindicated during pregnancy.

    The manufacturer does not recommend using esketamine during pregnancy. At the time of writing there is limited published information regarding the use of esketamine during pregnancy, a potential risk cannot be ruled out. Animal studies have shown neurotoxicity in developing foetuses.


    Esketamine is contraindicated during breastfeeding.

    The manufacturer advises that the patient either discontinues esketamine or discontinues breastfeeding taking into account the benefit of breastfeeding for the infant and the benefit of treatment for the mother. Animal data has shown excretion of esketamine in the breast milk however presence in human breast milk is unknown.

    Effects on Ability to Drive and Operate Machinery

    This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

    Side Effects

    Altered temperature sensation
    Blurred vision
    Desire to micturate
    Dry mouth
    Feeling abnormal
    Feeling drunk
    Impairment of mental skills
    Increased blood pressure
    Nasal discomfort
    Nasal dryness
    Nasal pruritus
    Oral hypoaesthesia
    Panic attack
    Perceptual disturbances


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: 20 October 2020

    Reference Sources

    Summary of Product Characteristics: Spravato 28mg nasal spray. Janssen Cilag Ltd. Revised July 2020. Government departments. Department for Transport. Publications. Drug driving and medicine: Advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at:
    Last accessed: 20 October 2020

    New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: Last accessed: 20 October 2020

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    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

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    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.