This week, the US Food and Drug Administration (FDA) approved esketamine, the first nasal spray to treat depression in adults who had tried other antidepressants unsuccessfully.  Esketamine, which has been approved by the FDA for use with an oral antidepressant, is marketed under the name Spravato. The drug is specifically approved for people with severe depression who have tried at least two antidepressants and have not responded to treatment (known as treatment-resistant depression), the FDA said in a press release . Treatment-resistant depression is a significant problem: Approximately 30 percent of people treated for depression are not relieved by standard treatments.
Esketamine is associated with ketamine, an anesthetic also used to treat treatment-resistant depression.
Ketamine is classified as Schedule III drug which means that it has a moderate to low dependence potential. Ketamine is an NMDA receptor antagonist and has been shown to relieve pain and produce some dissociative effects. You may have heard that it is referred to as a Special K in your free time.
Esketamine and ketamine are similar, but they are not identical, says Jamie Alan, PhD, Assistant Professor of Pharmacology and Toxicology at Michigan State University, to SELF. Both can be used as anesthetic, but esketamine is a stronger form of ketamine on some receptors in your brain. Ketamine and esketamine are also referred to as enantiomers which means that they are mirror images of each other at the molecular level.
Ketamine has been extensively studied for its antidepressant effects and IV-ketamine clinics are widely used in the US but have not yet been approved for the treatment of depression. There is some research that has linked IV use of ketamine to fast-acting depression, and sometimes even in less than 40 minutes, according to the National Institute of Mental Health . However, this is still considered to be an experimental use of ketamine which, unlike esketamine, is not FDA-approved for the treatment of depression; and that can have a significant impact on insurance coverage.
"While IV-Ketamine has been used in treatment-resistant depression for more than a decade, the type of delivery may be limited." Randall Espinoza, MD, MPH, a clinical clinic professor of psychiatry at the David Geffen School of Medicine at UCLA, says to SELF: "As a modified version of the drug, this new form is easier to administer and may have less dissociative side effects while reducing its effectiveness
The FDA There are strict guidelines for the approval of esketamine.
According to the FDA, the nasal spray is only available through a restricted distribution system as part of a Risk Assessment and Risk Reduction Strategy (REMS). This means that both you and your doctor must sign a patient registration form, knowing that you need help leaving the doctor's office and that you are not driving or operating a heavy device during the day after taking the drug
Esketamine It can only be taken under the supervision of a doctor in the office of your doctor, even though you give it to yourself after your doctor has shown you how to use it. Then you have to sit in the office for at least two hours until your doctor tells you to go. If you have treatment-resistant depression, your doctor may recommend it twice a week. "The procedure is time consuming, but it may be worth it for these patients," says Alan.
The FDA contributes to "the risk of serious adverse effects of sedation and dissociation" as well as "potential" for abuse and abuse of the drug. "Esketamine is also warned with the box that patients are at risk of being sedated, having problems with attention, and having problems with judgment, thinking, and suicidal thoughts and behaviors according to the FDA. The most common side effects of the drug in clinical trials were feeling disconnected from the mind and body, dizziness, nausea, sedation, dizziness, decreased sensation or sensitivity, anxiety, lethargy, high blood pressure, vomiting and drunkenness.
There is a reason why esketamine is taken with an oral antidepressant – it has been studied in clinical trials.
A randomized, double-blind, placebo-controlled trial published in the journal Biological Psychiatry in 2018 looked at 435 patients with treatment-resistant depression and either given them an esketamine twice daily or a placebo nasal spray together with an antidepressant. The researchers found that more than half of the participants who received the esketamine spray were considered remission after four weeks (ie they had no symptoms of depression).
Another study that was published in . American Journal of Psychiatry in 2018 was followed by 68 individuals who were randomly given 84 mg nasal or twice weekly placebo in addition to standard treatment (which generally includes an oral antidepressant) for four weeks. The researchers found that esketamine "in patients with risk of suicide can lead to a significant rapid improvement in depressive symptoms".
The reason that esketamine was only tested on an oral antidepressant is the question that it would be unethical to ask people who are severely depressed to discontinue their medication for a study, reports Danesh Alam, a psychiatrist and medical director for Behavioral Health at Northwestern Medicine Central DuPage Hospital, opposite SELF. "We may be conducting a study of taking them off all medications and trying esketamine, but there are concerns about what can happen," he says. Finally, the results of the clinical trials are "significant," even though esketamine has been used in addition to drugs the patients have already taken to show that the new drug works well.
"The availability of this new form of drug for treatment-resistant depression, especially for patients suffering from acute suicidal thinking is a significant advance and the first new treatment for depression in over 30 years," says Dr. Espinoza. He points out, however, that long-term data is missing. "The timing, longevity, and long-term effects still need to be finally investigated [and]." The persistence of the response is another open question, "he says.
While esketamine is currently only FDA-sanctioned for the treatment of patients with resistant depression. Alam that he may be opened in the future for people with […] high suicide risk – something he's just explored. If someone is suicidal, doctors will try to remove them from their environment (where they could possibly get hurt), start medications (like antidepressants), and wait for them to enter, which can take days or weeks. Dr Alam says. But esketamine works within hours. "There is a lot of potential with this drug," he says.