Acute short-term treatment of psychiatric emergency due to Major Depressive Disorder

Active Ingredient: Esketamine

Indication for Esketamine

Population group: only adults (18 - 65 years old)
Therapeutic intent: Curative procedure

Esketamine, co-administered with oral antidepressant therapy, is indicated in adults with a moderate to severe episode of Major Depressive Disorder, as acute short-term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency.

For this indication, competent medicine agencies globally authorize below treatments:

84 mg twice per week for 4 weeks

For:

Dosage regimens

Nasal, 84 milligrams esketamine, 2 times weekly, over the duration of 4 weeks.

Detailed description

Assessment before treatment

Prior to dosing with esketamine blood pressure should be assessed.

If baseline blood pressure is elevated the risks of short-term increases in blood pressure and benefit of esketamine treatment should be considered. Esketamine should not be administered if an increase in blood pressure or intracranial pressure poses a serious risk.

Patients with clinically significant or unstable cardiovascular or respiratory conditions require additional precautions. In these patients, esketamine should be administered in a setting where appropriate resuscitation equipment and healthcare professionals with training in cardiopulmonary resuscitation are available.

Post-administration observation

After dosing with esketamine, blood pressure should be reassessed at approximately 40 minutes and subsequently as clinically warranted.

Because of 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.

Posology

The recommended dosage for adult patients (<65 years) is 84 mg twice per week for 4 weeks. Dosage reduction to 56 mg should be made based on tolerability. After 4 weeks of treatment with Spravato, the oral antidepressant (AD) therapy should be continued, per clinical judgement.

In these patients, treatment with Spravato should be part of the comprehensive clinical care plan.

Food and liquid intake recommendations prior to administration

Since some patients may experience nausea and vomiting after administration of esketamine, patients should be advised not to eat for at least 2 hours before administration and not to drink liquids at least 30 minutes prior to administration.

Nasal corticosteroid or nasal decongestant

Patients who require a nasal corticosteroid or nasal decongestant on a dosing day should be advised not to administer these medicinal products within 1 hour before esketamine administration.

Missed treatment session(s)

Patients who have missed treatment session(s) during the first 4 weeks of treatment should continue with their current dosing schedule.

For patients with treatment-resistant Major Depressive Disorder who miss treatment session(s) during maintenance phase and have worsening of depression symptoms, per clinical judgement, consider returning to the previous dosing schedule.

Dosage considerations

Sneezing after administration

If sneezing occurs immediately after administration, a replacement device should not be used.

Use of the same nostril for 2 consecutive sprays

If administration in the same nostril occurs, a replacement device should not be used.

Treatment discontinuation does not require tapering off; based on data from clinical trials the risk of withdrawal symptoms is low.

Active ingredient

Esketamine

Esketamine is the S-enantiomer of racemic ketamine. It is a non-selective, non-competitive, antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. Through NMDA receptor antagonism, esketamine produces a transient increase in glutamate release leading to increases in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) stimulation and subsequently to increases in neurotrophic signalling which may contribute to the restoration of synaptic function in these brain regions involved with the regulation of mood and emotional behaviour. Restoration of dopaminergic neurotransmission in brain regions involved in the reward and motivation, and decreased stimulation of brain regions involved in anhedonia, may contribute to the rapid response.

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