Spravato (esketamine) nasal spray

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved March 2019

Specific Treatments:

treatment-resistant depression in adults

Therapeutic Areas

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General Information

Spravato (esketamine) nasal spray is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist. 

Spravato is specifically indicated for use, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults.

Spravato is supplied as a spray for intranasal administration. The recommended dosage is as follows:

Induction Phase Weeks 1 to 4: Administer twice per week; Day 1 starting dose: 56 mg followed by subsequent doses of 56 mg or 84 mg

Maintenance Phase Weeks 5 to 8: Administer once weekly at 56 mg or 84 mg. Week 9 and after: Administer every 2 weeks or once weekly at 56 mg or 84 mg. Dosing frequency should be individualized to the least frequent dosing to maintain remission/response.

Clinical Results

FDA Approval

The FDA approval of Spravato was based on three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. All patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.

Side Effects

Adverse effects associated with the use of Spravato may include, but are not limited to, the following:

dissociation

dizziness

nausea

sedation

vertigo

hypoesthesia

anxiety

lethargy

blood pressure increased

vomiting

feeling drunk

The Spravato drug label comes with the following Black Box Warning: Risk for sedation and dissociation after administration. Monitor patients for at least two hours after administration. ● Potential for abuse and misuse. Consider the risks and benefits of prescribing Spravato prior to using in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse. ● Spravato is only available through a restricted program called the Spravato REMS. ● Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Spravato is not approved for use in pediatric patients. 

Mechanism of Action

Spravato (esketamine), the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown. The major circulating metabolite of esketamine (noresketamine) demonstrated activity at the same receptor with less affinity.

Additional Information

For additional information regarding Spravato or treatment-resistant depression in adults, please visit https://www.spravato.com/