Medication Monitor



Generic Name (Trade Name—Company)
Notes
March 6, 2019

Esketamine nasal spray

(Spravato—Janssen)
FDA approves new nasal spray medication for treatment-resistant depression

FDA has approved esketamine nasal spray, in conjunction with an oral antidepressant, to treat depression in adults who have not benefited from other antidepressants. Esketamine is the s-enantiomer of ketamine ([Ketalar] approved in 1970), which is a mixture of two enantiomers (mirror-image molecules). This is the first FDA approval of esketamine for any use.

Because of the potential for serious adverse outcomes resulting from sedation and dissociation, the drug will be available only through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (REMS). Esketamine must also be dispensed with a patient Medication Guide that outlines the drug’s uses and risks. 

Patients self-administer esketamine nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider instructs the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave. Patients must be monitored by a health care provider for at least 2 hours after receiving their esketamine dose.  

Efficacy of esketamine was evaluated in three short-term (4-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive esketamine or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, 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, esketamine nasal spray demonstrated statistically significant effect compared with placebo on the severity of depression, and some effect was seen within 2 days. The two other short-term trials did not meet the prespecified 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 esketamine 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.

The most common adverse effects in clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.

Patients with unstable or poorly controlled hypertension or preexisting aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Because the drug may cause fetal harm, women of reproductive potential should consider pregnancy planning and prevention, and women should not breastfeed while being treated.

FDA granted this drug application Fast Track and Breakthrough Therapy designations.