The spray (Spravato; Janssen Pharmaceuticals) will come in tamper-resistant prepackaged units of one, two, or three devices to deliver the prescribed doses of 28 mg, 56 mg, or 84 mg, respectively. To reduce the risk of diversion, misuse, or abuse, the drug will managed under an FDA Risk Evaluation and Management Strategy (REMS). It will only be available to prescribing clinicians who have undergone training on the risks of esketamine and the importance of monitoring patients after their dose is administered. Facilities licensed to dispense esketamine must have the ability to medically monitor patients for at least 2 hours after administration. Patients will self-administer the spray and will not be able to take any of it home.
The REMS will require both prescriber and the patient to both sign a Patient Enrollment Form clearly stating that patients understand the necessity of assisted transport to leave the health care facility and that there should be no driving or use of heavy machinery for the rest of the day on which they are treated.
A boxed warning on the label will note that patients are at risk for sedation and difficulty with attention, judgment, and thinking (dissociation); abuse and misuse; and suicidal thoughts and behaviors after administration of the drug.
Despite the FDA’s caveats, the approval of intranasal esketamine is seen as a substantial win for the psychiatric community, Tiffany Farchione, MD, acting director of the FDA division of psychiatry products, said in a statement. “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition.”
“Spravato has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies,” said Mathai Mammen, MD, PhD, global head of Janssen Research and Development.
The company “is working quickly to educate and certify treatment centers in accordance with the REMS so that health care providers can offer Spravato to appropriate patients,” according to a statement from Janssen. “Later this month, patients can visit www.SPRAVATO.com for a locater tool and to sign up to receive alerts when new treatment centers are available.”
Intranasal esketamine was evaluated in three short-term clinical trials and one longer-term maintenance-of-effect trial. One of the studies demonstrated a clinically significant effect in depression severity, in as little as 2 days for some patients. The two other short-term trials did not show significant benefit. However, in the maintenance study, patients in stable remission or with stable response who continued treatment with esketamine plus an oral antidepressant experienced a significantly longer time to relapse of depressive symptoms than patients on placebo spray plus an oral antidepressant. The most common side effects were disassociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders might be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine might impair attention, judgment, thinking, reaction speed, and motor skills. It may cause fetal harm; women of childbearing age should be on reliable contraception. Breastfeeding women should not use it.
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