Esketamine Nasal Spray

From 1 May 2025, esketamine nasal spray became available on the Pharmaceutical Benefits Scheme (PBS) for treatment-resistant major depression.

Intravenous and subcutaneously administered ketamine has been used off-label for this purpose. Ketamine is thought to exert its effect in depression primarily via antagonism of the N-methyl-D-aspartate (NMDA) receptor. Ketamine is a racemic mixture, containing equal parts of the S-enantiomer and R-enantiomer. Studies demonstrate that esketamine, the S-enantiomer of ketamine, has a higher affinity for the NMDA receptor.

Short-term studies demonstrate that esketamine plus a newly initiated oral antidepressant provides clinically meaningful improvement in depressive symptoms compared to an antidepressant plus placebo nasal spray. In some cases, symptom reduction was apparent at 24 hours after the first dose and continued throughout the four-week trials. Long-term studies demonstrate that patients in stable remission who continued with esketamine plus an oral antidepressant were 51% less likely to relapse compared to patients who continued the oral antidepressant but were switched to the placebo nasal spray.

Esketamine must be prescribed by a psychiatrist and be started in combination with a newly initiated oral antidepressant. Esketamine nasal spray can be self-administered, but this must always occur under the direct supervision of a healthcare professional at an accredited treatment centre. Supervised administration reduces the risk of abuse, misuse, and diversion. It also allows appropriate monitoring for adverse effects, such as elevated blood pressure, sedation, and dissociation.

Esketamine is presented in a single-use device that delivers 28 mg of esketamine in two actuations. One spray is administered into each nostril, and patients should then rest in a semi-reclined position for five minutes. If more than one device is required, a five-minute rest should be taken between each device to facilitate absorption.