Approved esketamine CIII ASAP spray (Spravato) for use in conjunction with an oral antidepressant in adults with treatment-resistant depression (TRD).

A non-competitive antagonist of glutamate receptors of the N-methyl-D-aspartate (NMDA) type.

Esketamine works by targeting the N-methyl-D-aspartate (NMDA) receptor in the brain, which regulates the release of neurotransmitters like serotonin and dopamine.

Unlike traditional antidepressant medications, which can take weeks to start working, Esketamine has been shown to start working within hours to days, with significant improvements in mood, energy, and motivation.

With more than 1700 adults with TRD who took Esketamie and an oral antidepressant experienced superior improvement in depression symptoms at 4 weeks, compared to those who received a placebo and an oral antidepressant.

Patients in stable remission taking the medication who continued treatment with the medicine were 51% less likely to relapse versus those who maintained a regimen of a placebo and an oral antidepressant.

Esketamine nasal spray rapidly reduces depressive symptoms in patients at imminent risk of suicide, according to two placebo-controlled, phase 3 trials.


ASPIRE-1 and ASPIRE-2, randomized adults with major depressive disorder who had active suicidal ideation with intent and required psychiatric hospitalization, to 84 mg of esketamine nasal spray twice a week or placebo over 4 weeks. 


At Twenty-four hours after the first dose, patients who received esketamine showed significant improvement in a depression  total score, compared with patients who received placebo.


Common adverse events with esketamine were dizziness, dissociation, and nausea.

Patients with major depressive disease are considered to have treatment resistant disease if they have not responded adequately to at least 2 different antidepressants of adequate dose and duration in the current depressive episode.

Approximately one-third of US adults with major depressive disease have treatment resistant disease.

Esketamine requires a Risk Evaluation and Mitigation Strategy (REMS) and its use has the risk of suicidal thoughts and behaviors in pediatric patients and young adults.

The most common side effects when used along with an antidepressant taken by mouth included: dissociation, dizziness, nausea, sedation, spinning sensation, reduced sense of touch and sensation, anxiety, lack of energy, increased blood pressure, vomiting, and feeling drunk.

The medication is dispensed directly to patients for home use.

The patient is observed for treatment-emergent sedation, dissociation and blood pressure changes for at least 2 hours, until the patient is safe.

Patients should not drive or operate heavy machinery until the next day, following a restful sleep.

It may have a transient effect on blood pressure and heart rate and can reduce feelings of dissociation lasting 1-2 hours.

Long term use of the nasal spray in combination with an anti-depressant was more effective than an oral anti-depressant inpreventing relapse in patients with treatment resistant depression.

Esketamine nasal spray plus a selective serotonin reuptake inhibitor or a serotonin norepinephrine reuptake inhibitor are superior to extended release quetiapine plus an SSRI or SNRI with respect to remission at eight weeks (Reif A).

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