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In clinical trials, six patients who were taking the drug died, three from suicide, but FDA background materials reviewed by the advisory committee that recommended approval last monthsaid, It is difficult to consider these deaths as drug-related.
Because of the drugs close relationship to ketamine, experts have raised concerns about its potential for misuse and abuse, but clinical trials found those risks to be unfounded.
Concerns have also been raised about a lack of long-term data on possible health effects, most notably cognitive ones.
The drug was designated as a breakthrough therapy in 2013, a status intended to expedite the development and review of drugs for serious or life-threatening conditions, the FDA said at the time.
Greg Panico, a spokesman for Janssen, a division of Johnson & Johnson, did not say when Spravato will be available. He wrote in an email, We are working quickly to educate and certify treatment centers on the unique administration requirements of SPRAVATO to ensure patients can access this important medicine.
As for the cost, it will be generally comparable with other specialty mental health drugs, Panico said: about $590 to $885 per treatment session, based on the dosage and not accounting for mandatory discounts or negotiated rebates.
CNNs Michael Nedelman and Ben Tinker contributed to this report.
Fda Approves Spravato To Treat Major Depressive Disorder
Spravato is considered the first big advancement in depression treatment since the approval of Prozac and it just got approved for a new use.
Approved for treatment-resistant depression in March of 2019, esketamine is now approved to treat depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior.
Dozens of antidepressants have been approved over the years. These include Eli Lillys blockbuster drug Prozac, which was approved in 1987. But there haven’t been any new advancements in other types of antidepressants that work in different ways.
Esketamine offers the first new mechanism of action in 30 years to treat MDD.
Since its initial approval, esketamine has been prescribed to about 6,000 patients.
This medication is available as a nasal spray and is to be given with an oral antidepressant . The recommended dose is 84 mg twice per week for four weeks. After four weeks, your health care provider will evaluate the benefit and decide whether you will need to continue treatment.
The FDA approved the new use for this drug based on data from two phase 3 trials. The trials found that people who were given esketamine plus standard care had reduced depressive symptoms within 24 hours.
The effectiveness of esketamine in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated, according to Janssen.
Esketamine’s new indication approval was granted to Janssen Pharmaceuticals, Inc.
Approved Nasal Spray Gives Hope To Patients With Severe Depression
- New York, NY
An antidepressant inhaled as a nasal spray is the first drug approved in 30 years that acts on a different chemical system in the brain than previous medications, and is aimed at patients whose condition is so overwhelming it puts them at risk of suicide. The nasal spray delivery method is a first of its kind. Esketamine represents the first new category of medication for depression in over 30 years, so we are all very excited by this milestone, said Eric Nestler, PhD, director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. We need to better understand how the drug works in different populations of patients. And we need to better understand how exerts its antidepressant effects so that orally available medications can be developed.”
Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, President, Academic Affairs, Mount Sinai Health System
Eric J. Nestler, MD, PhD, Dean, Academic and Scientific Affairs, Director, Friedman Brain Institute, Professor, Neuroscience, Psychiatry, Pharmacological Sciences, Icahn School of Medicine at Mount Sinai
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Fda Approves Spravato A Fast
The first new class of antidepressant drugs in more than three decades was approved in March when the U.S. Food and Drug Administration fast-tracked esketamine, the chemical cousin of illegal street drug ketamine, to prescribe to patients with treatment-resistant depression.
Developed by Johnson & Johnsons subsidiary, Janssen Pharmaceuticals, esketamine is marketed under the name Spravato and dispensed as a nasal spray administered under the supervision of trained health care professionals.
Ketamine is the chemical mixture of esketamine and arketamine, two mirror-image molecules. But when the molecules are separated, esketamine has been shown to be more potent. As a result, it requires a lower dosage and has a decreased risk of disassociation, tolerance and abuse.
Thats why Janssen preferred to develop esketamine. It has more robust antidepressant efficacy with less side effects, said Rodrigo Machado-Vieira, M.D., Ph.D., professor of psychiatry and behavioral sciences and director of the Experimental Therapeutics and Molecular Pathophysiology Program at UTHealth Harris County Psychiatric Center. Its the most striking discovery in psychiatry in the past 34 years at least, so Im very excited.
Spravato is for patients who have tried but do not respond to at least two antidepressants. While all the other antidepressants on the market take two to three weeks to take effect, esketamine and ketamine work in a matter of hours.
How Well Does Esketamine Work Compared To Other Popular Antidepressants
Traditional antidepressant pills can take 2 4 weeks to take effect. Several weeks can be a long time to wait for an improvement in symptoms, especially if the antidepressant causes side effects such as nausea, stomach upset, dry mouth, sleeplessness or drowsinesswhich many do. Add to that frustration the fact that 60% 70% of sufferers will not respond to the first treatment they try, and the situation can get pretty desperate.
The main benefit of esketamine is that it causes a fastwithin hours and daysimprovement in the symptoms of depression. This is a major shift in treatment options for sufferers who could feel that they are running out of options. The nasal spray helps esketamine get absorbed faster than taking a pill. It is givenin the doctors officetwice a week for the first month, and then every week or every other week after that.
So, a new antidepressant that works fast to save lives where others fail? Whats not to be excited about?
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Concern For Abuse And Withdrawal
Despite the promising results of the study, questions remain about the drugs safety.
In an accompanying editorial in the same issue of the American Journal of Psychiatry, Dr. Alan F. Schatzberg, the Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, expresses some of those concerns.
Its not clear to me that we really understand whats the optimal way of using it, how much we should give, how long we should give it for, what we should do when we stop it, Schatzberg told Healthline.
That doesnt mean that someone shouldnt go ahead and use it. But I think there has to be a modicum of caution that we dont really have all the answers, he added.
Schatzbergs biggest concerns include the potential for abuse and issues with withdrawal. He suggests that, like opioids, there is the potential to have adverse health events when discontinuing use.
In a statement sent to Healthline, a spokeswoman for Janssen pointed out that Spravato nasal spray is the first new mechanism of action for an antidepressant medication in decades, and that prior to this physicians have had limited options to help patients with treatment-resistant depression.
Ketaminefrom Anesthetic To Depression Miracle Drug
Interestingly, studies from Yale research labs showed that the drug ketamine, which was widely used as anesthesia during surgeries, triggers glutamate production, which, in a complex, cascading series of events, prompts the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, and gives patients the opportunity to develop more positive thoughts and behaviors. This was an effect that had not been seen before, even with traditional antidepressants.
I think the interesting and exciting part of this discovery is that it came largely out of basic neuroscience research, instead of by chance, says Gerard Sanacora, MD, PhD, a psychiatrist at Yale Medicine who was also involved in many of the ketamine studies. It wasnt just, lets try this drug and see what happens. There was increasing evidence suggesting that there was some abnormality within the glutamatergic system in the brains of people suffering from depression, and this prompted the idea of using a drug that targets this system.
This is why Dr. Sanacora believes that ketamine may be most effective when combined with cognitive behavioral therapy . CBT is a type of psychotherapy that helps patients learn more productive attitudes and behaviors. Ongoing research, including clinical trials, addressing this idea are currently underway here at Yale.
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Depression: A New Nasal Spray Is Considered A Breakthrough Treatment
No one took the initial findings seriously. In the 1990s, Dr. Dennis Charney and a coworker, Dr. John Krystal, were doing research on antidepressants at Yale. The majority of them focused on neurotransmitters in the brain namely serotonin, norepinephrine, and dopamine.
We ended up thinking that couldnt be the conclusion because those medicines take weeks or months to take effect and dont work in many people, so we moved on, Charney said. ICSID was founded by a passionate believer in international trade who hoped it would strike an even broader patha life-saving medicine for children afflicted with bone cancer, he added.
After testing a variety of possibilities, the scientists discovered that ionotropic glutamate receptors may also be involved. It turns out that ketamine has an impact on these receptors.
The researchers investigated whether the drug may be used for Depression Treatment and discovered that it began working within a few hours. Charney claims that even he was shocked by the findings. This weeks work on ketamine has resulted in another achievement.
They created a treatment and licensed it to Janssen Pharmaceuticals, which is marketing the esketamine nasal spray under the brand name Spravato. The medication will be available solely to adults who have treatment-resistant depression and who are taking an oral antidepressant.
Package Advice Esketamine Nasal Spray For The Treatment Of Adults With Treatment
Zorginstituut Nederland has completed its assessment whether esketamine nasal spray can be included in the insured package. The treatment is indicated for the treatment of adults with treatment-resistant major depressive disorder. Due to its expected high costs the Minister of Medical Care and Sports has placed the treatment in the so-called package lock or sluice for expensive drugs. These products can only be accepted into the insured package after the Zorginstituut has advised on their inclusion in the insured package and, where applicable, subject to Ministry negotiations to arrive at a financial arrangement with the supplier.
Zorginstituut Nederland has concluded that esketamine nasal spray should be included in the basic health care package, but as the 4th step of the treatment algorithm, after successful price negotiations, preferably in the form of pay for performance or pay for proof agreements.
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Esketamine And Racemic Ketamine
Some research shows a new drug called ketamine is effective in the treatment of depression. Ketamine is available in two forms: Esketamine and racemic ketamine. Racemic ketamine has been shown to improve both typical and atypical symptoms of depression.
It is not clear how effective racemic ketamine is compared to esketamine .
However, new research by Bahji and colleaguesfrom Queens University in Canada and the National Institute of Mental Health in the USsuggests racemic ketamine might be more effective than esketamine. Published in the January 2021 issue of Journal of Affective Disorders, the article reports the results of the first systematic review and meta-analysis that has compared the performance of intravenous ketamine to intranasal esketamine for the treatment of unipolar and bipolardepression.
It should be noted that esketamine was approved by the US Food and Drug Administration for the treatment of depression in 2019. Ketamine infusion has been used off-label only and has yet to be approved by the FDA. Does this mean IV ketamine is necessarily inferior to Spravato? For an answer to this question, let us examine the findings of the paper by Bahji et al.
Why Is This Medication Prescribed
Esketamine nasal spray is used along with another antidepressant, taken by mouth, to manage treatment-resistant depression in adults. It is also used along with another antidepressant, taken by mouth, to treat depressive symptoms in adults with major depressive disorder and suicidal thoughts or actions. Esketamine is in a class of medications called NMDA receptor antagonists. It works by changing the activity of certain natural substances in the brain.
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Who Is A Good Candidate For Esketamine Therapy
Currently, esketamine is approved for people with treatment-resistant depression. That means youve tried at least two other antidepressants and havent experienced remission or at least a 50% improvement in mood.
For people who havent had success with other antidepressants, esketamine gives them the chance to see what its like to not have depression, says Kaplin. It gives them hope that they can feel better with the right treatment.
Q& a With Dr Steve Levine Psychiatrist Ketamine Expert And Founder Of Actify Neurotherapies
Q: How does ketamine work to positively impact depression and anxiety?
A: Depression and anxiety result in the loss of the number, function, and quality of important brain connections. Ketamine is able to quickly produce proteins that repair those connections.
Q: How does Esketamine treatment differ from ketamine IV infusions?
A: Like ketamine IV infusions, nasal Esketamine will only be allowed to be administered in a specially certified medical setting. Patients will remain in the office for two hours after administration, and then not be able to drive until the next day. Most patients do recover quickly, and may be able to return to work or other activities the same day.
Q: What patients typically respond best to ketamine?
A: Ketamine and Esketamine are appropriate for those with depression who have not responded to other treatments. It seems to work particularly well for those who also have anxiety or suicidal thoughts. For now, Esketamine is indicated for those who have tried at least two other treatments. Consult your doctor about whether Esketamine and ketamine IV infusion treatment is right for you.
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What Is Esketamine And Why Do We Need It
Esketamine nasal spray will be used solely to treat adults with depression who have tried at least two other antidepressants without success. The drug works by binding to NMDA-receptors in the brain, blocking the reuptake of glutamate while activating AMPA receptors. In short, they strengthen synapses in the areas of the brain associated with motivation and mood.
Studies show that 30% of depression sufferers don’t see results from standard depression treatment options. It’s also clear that patients who don’t respond to antidepressant medications are at higher risk of suicide than those who are treatment-responsive.
What’s more, unlike oral antidepressants , esketamine is fast-acting. Patients may see relief from severe depression symptoms within hours. This is what makes the drug so impactful for individuals with severe depression, especially as many of the SSRIs and more traditional tricyclic antidepressants on the market come with significant side-effects.
During clinical trials, researchers found that esketamine, when taken by patients at risk of suicide, resulted in “significantly rapid improvement in depressive symptoms.” The effects of treatment were also long-lasting, with many patients requiring no more than a single dose per week.
What Are Common Side Effects Of Esketamine
Esketamine is not a miracle drug. It has a high risk for misuse, and higher doses can cause a frightening and dangerous state of mind-body dissociation, where the user cannot speak or move and can become psychotic or comatose in extreme cases.
Even under a doctors supervision, there is a risk of blood pressure spikes and distressing, out-of-body experiences, as well as headaches and nausea.
The thing that concerns some experts most about esketamine is the absence of long-term evidence about its safety.
There is also the fact that this new treatment plays into the current hype surrounding ketamine as some kind of miracle cure for depression. Some experts worry that the hype will discourage depression sufferers from trying traditional, safer first-line antidepressants, favoring instead the quick fix promised by esketamine.
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Its Effective For Treatment
Up to 33% of people with depression dont respond to multiple kinds of conventional antidepressants. Esketamine reduces depression symptoms in a majority of these people in clinical trials.
The only other approved drug therapy for treatment-resistant depression is a combination of olanzapine and fluoxetine . However, this treatment has significant long-term effects that include substantial weight gain, metabolic changes, diabetes and high blood pressure.
How Much Does Esketamine Nasal Spray Cost
The cost of Spravato treatment will depend on the dose needed. Initial estimates are between $590 and $885 per treatment session. But added to that will be the cost of the visitesketamine can only be administered in the doctors office under close supervision. In comparison, popular antidepressants like , , , and duloxetine currently cost about $10 $20 with a GoodRx coupon for a typical 30-day supply.
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Fda Advisory Panel Endorses Breakthrough Nasal Spray Treatment For Depression
The problem, critics say, is that the drugs manufacturer, Janssen, provided the FDA at best modest evidence it worked and then only in limited trials. It presented no information about the safety of Spravato for long-term use beyond 60 weeks. And three patients who received the drug died by suicide during clinical trials, compared with none in the control group, raising red flags Janssen and the FDA dismissed.
The FDA, under political pressure to rapidly greenlight drugs that treat life-threatening conditions, approved it anyway. And, though Spravatos appearance on the market was greeted with public applause, some deep misgivings were expressed at its day-long review meeting and in the agencys own briefing materials, according to public recordings, documents and interviews with participants, KHN found.
Dr. Jess Fiedorowicz, director of the Mood Disorders Center at the University of Iowa and a member of the FDA advisory committee that reviewed the drug, described its benefit as almost certainly exaggerated after hearing the evidence.
Fiedorowicz said he expected at least a split decision by the committee. And then it went strongly in favor, which surprised me, he said in an interview.
Esketamines trajectory to approval shows step by step how drugmakers can take advantage of shortcuts in the FDA process with the agencys blessing and maneuver through safety and efficacy reviews to bring a lucrative drug to market.