The Food and Drug Administration (FDA) has approved esketamine (Spravato) for patients with major depressive disorder who have not responded to treatment with at least two other antidepressant drugs. Esketamine is administered nasally and is given in conjunction with an oral antidepressant. Because there is a risk of serious adverse effects with esketamine, the drug must be administered in a medical office or clinic that has been certified through the FDA's Risk Evaluation and Mitigation Strategy (REMS) program.

Esketamine was studied in both short- and long-term randomized, double-blind, placebo-controlled clinical trials. Compared with patients who received placebo plus an antidepressant, those who received esketamine plus another antidepressant had significant reductions in depressive symptoms in the short-term trial and remained in stable remission from depression for longer in the long-term trial.

The most common adverse effects from esketamine in clinical trials were dissociation (problems with attention, judgment, and thinking; distortion of time and space; derealization and depersonalization), dizziness, nausea, sedation, vertigo, hypoesthesia (reduced sense of touch, numbness), anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk. The drug also carries a risk of embryo-fetal toxicity and of ulcerative or interstitial cystitis. It is contraindicated in patients with a history of any type of aneurysmal disease, intracerebral hemorrhage, or hypersensitivity to ketamine or esketamine. Physical dependence and tolerance have been reported with frequent, large doses of ketamine and could be possible with esketamine if abused or misused. For these reasons, it is classified as a controlled substance. The drug carries a black box warning concerning the risk of sedation, dissociation, abuse and misuse, and, like all antidepressants, increased suicidal ideation.

The recommended esketamine dosing is twice a week for the first month and weekly for the second month, progressing to a maintenance dose of every week or every two weeks in the third month. The drug comes in a prefilled device for nasal administration. Each device contains two sprays, one for each nostril, and should not be primed, as part of the dose will be lost.

Patients must be monitored for at least two hours after receiving the drug. Blood pressure should be assessed prior to administration; if it is elevated (140/90 mmHg or greater), the dose may need to be delayed. Blood pressure must be reassessed 40 minutes after administration, when the medication peaks. Substantial increases in blood pressure can occur even if blood pressure did not increase after previous doses of esketamine. If patients develop hypertensive crisis, they should be transferred immediately for emergency care. The nurse or NP should also assess patients for significant sedation or psychological effects for at least two hours after administration. Patients who've received esketamine should not drive until the following day. Patients must not be allowed to remove esketamine from the health care setting.

To read the full drug label, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf.