For Immediate Release
March 5, 2019
Release
The U.S. Food and Drug Administration today approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”
Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.
The Spravato labeling contains a Boxed Warning that cautions 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. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks.
The patient self-administers Spravato 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 will instruct 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.
The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato 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, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified 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 Spravato 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 side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato 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. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.
Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.
The FDA granted this application Fast Track and Breakthrough Therapydesignations.
The FDA granted the approval of Spravato to Janssen Pharmaceuticals, Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Gonna be interesting to see how this new mode of treatment will be arranged.
Sounds like the patient will be still be coming into your office to initiate the treatment.
And it will be a several hour visit.
If you’re going to be in the office that long, might you go ahead and take the IV Ketamine instead?
Perhaps insurance will cover costs now.?.
Must be less costly to administer than hooking up IV’s.
Yes, this treatment must be administered in a doctor’s office or clinic or hospital, and the regulations state that the patient must be monitored for 2 hours. We’ll still offer both treatment options, and I expect that many patient will want infusions because they are so rapid and effective, and infusions can be onto existing medications or used if a patient is not on an antidepressant medication. Esketamine must be given with a new antidepressant, and the time in the office will end up being a few hours–more than with most infusions. We hope that insurance coverage and reimbursement for this will make it more available to everyone who could benefit from it.
Is this nasal spray available through the order of any psychiatrist?
I definitely meet the criteria.
Depression and anxiety have consumed most of my adult life.
Yes, it is. Psychiatrists have to be registered in order to provide this to their patients, and then have to register each patient in order to have the medication shipped. We received our registration and will get instructions shortly on ordering, so the process is in place, up and already rolling. We’ll know in a day or two what the next steps are for ordering.
Hello,
I’m a 23 year old male with treatment-resistant depression that has been closely following the development of esketamine over the last two years. I’m quite happy that this breakthrough treatment has now been approved, but I’m curious how long it will take to reach market now that approval has been granted. Might you have any additional insight on this?
Doctors need to be registered to be able to provide Spravato and then need to register patients for this treatment in order for it to be shipped to the doctor’s office. Our office is set up, ready to go, and registered. We’re waiting for the final last few steps in this process and then we’ll begin reaching out to the people who’ve called and are on our waiting list. I hope to hear back in a day or two about the next steps so please stay in touch with us.
This new approval is a little frustrating to me. I really wish the FDA would approve the IV infusion route. This is the original and proven way of administration. Infusions have the most stable absorption. So, I guess the only way to be covered by insurance is to use the nasal spray. I personally do not want to use the spray. I want to stay with the infusions. I am wondering why the FDA approved a method of variable and unpredictable absorption where the patient has to stay in the office even longer than with the IV infusions. I don’t mean to be cynical, but I am thinking the reason has to do with grants, politics, big pharma.
This is wonderful news for those of us who cannot afford the infusions in my opinion. I look forward to it.