Health Problem: Major depressive disorder (MDD), a serious and life-threatening condition, is one of the most common mental disorders in the United States and a leading cause of disability worldwide. MDD is a chronic disease associated with high rates of morbidity and excess mortality. Approximately 30% to 40% of patients fail to respond to first-line treatment, including oral antidepressants or psychotherapy. Treatment resistant MDD is typically defined as depression that does not respond to at least 2 attempts of treatment of adequate dose and duration with antidepressants; however, there is no official consensus regarding the definition.
Technology Description: The drug-device combination comprises esketamine for intranasal administration intended for the treatment of treatment resistant MDD. Esketamine is the S-enantiomer of ketamine, a Food and Drug Administration–approved general anesthetic agent. Ketamine is an N-methyl-D-aspartate glutamate (NMDA) receptor antagonist that enhances glutamine release in the brain. Esketamine has greater affinity for the NMDA receptor and greater dopamine transporter inhibition than ketamine; it is a more potent anesthetic than ketamine but has a more rapid metabolism. Esketamine is available in a nasal spray device that delivers 2 sprays (1 spray for each nostril) containing a total of 28 milligrams (mg) of esketamine. Larger doses may be delivered by using 2 (56 mg dose) or 3 (84 mg dose) devices with a 5-minute rest between use of each device.
Controversy: Ketamine has been identified as a drug of abuse by the Drug Enforcement Agency; it is a schedule III non-narcotic substance under the Controlled Substances Act. Esketamine has also been designated a schedule III controlled substance and may be subject to abuse and diversion. As a treatment, esketamine has the potential to be a disruptive therapy; treatment requires that a healthcare professional monitor patients when they self-administer the medication and patients must continue to be monitored for transient dissociative and blood pressure changes prior to leaving the healthcare setting.
Key Questions:
Is esketamine as an adjunct to an oral antidepressant effective in reducing symptoms of major depressive disorder (MDD) in patients with treatment-resistant depression (TRD)?
How does esketamine as an adjunct to an oral antidepressant compare with alternative treatments for treatment-resistant MDD?
Is esketamine as an adjunct to an oral antidepressant safe?
Have definitive patient selection criteria been established for esketamine as an adjunct to an oral antidepressant in patients with treatment-resistant MDD?
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