A first-of-its-kind treatment for depression got a big nod on Tuesday from a group of scientists convened by the US Food and Drug Administration. Experts concluded that the drug, called esketamine and inspired by ketamine, is safe and effective and said its benefits outweighed its risks. Their input will play a key role in the FDA's final approval decision, expected in March. If given the official green light, the drug would be the first novel therapeutic for depression in 35 years. A drug inspired by ketamine, which has been called "the most important discovery in half a century," is on the cusp of becoming the first new kind of depression medication in 35 years. Called esketamine and developed by Johnson & Johnson, the drug is a nasal spray designed to treat severe forms of depression that don't respond to other medications. It's the chemical mirror image of ketamine and thought to have slightly fewer side effects than the original compound. On Tuesday, a panel of experts convened by the Food and Drug Administration voted 14-2 in favor of the drug's effectiveness and 15-2 in favor of its safety. Their recommendation will play a key role in the FDA's approval decision, expected in March. Additionally, they voted 14-2 that the drug's benefits outweighed its risks. "I think there's substantial evidence that this could be a game-changer," Steven Meisel, a system director of medication safety with Fairview Health Services who was one of the panel's 17 voting members, said on Tuesday. If the FDA approves the drug, it would be the first federally approved depression drug in nearly four decades to work differently than depression medications on the market. That's a significant milestone. Depression is the world's leading cause of poor health and disability, and as many as one in three patients don't get relief from existing antidepressants. Analysts are hopeful that Johnson & Johnson's new drug could help. "Ultimately, we think [esketamine's] risk-benefit profile favors approval, especially in a disease paradigm where little options are available," Carter Gould, the executive director of biotech equity research at UBS, wrote in a note circulated last week. The emerging science on ketamine A growing list of academic medical centers, including Columbia University, offer ketamine to patients with severe depression. Columbia Doctors Whether it's Abilify or Zoloft, almost all antidepressants work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in our mood. Ketamine appears to engage a different part of the brain than traditional antidepressants, which is part of the reason it's been called "the most important discovery in half a century" for mental illness. The drug's apparent rapid-fire effects may be especially useful for staunching suicidal thinking in people who are considering taking their own lives, experts say. Ketamine also has long been used to prevent pain, which suggests to clinicians that it's relatively safe. "There is nothing approved that gets patients better this fast," Walter S. Dunn, a psychiatrist and assistant clinical professor at the University of California Los Angeles who was also one of the panel's voting members, said on Tuesday. But right now, ketamine is neither cheap nor quick to administer. Because it's given through an IV drip, the process can take 45 minutes to two hours. Each session costs $500 to $750 and is not covered by insurance, because ketamine is approved in the US only for use as an anesthetic. People given ketamine for depression are typically advised to get eight to 12 sessions, bringing the total cost to as much as $9,000. Ketamine and esketamine also have some negative side effects. The most troublesome, according to analysts and scientists, is the drugs' tendency to produce what's known as dissociative — or "out of body" — experiences. Experts worry that some patients could react negatively to the experience and then avoid the drug, or react positively and want to repeatedly use it, potentially leading to a drug-use disorder. Experts on the FDA panel said no misuse or abuse was seen in Johnson & Johnson's clinical trials, however, adding that they considered the risk of abuse among adults to be low. Read more: A 'party drug' with potential to be the next blockbuster antidepressant is edging closer to the mainstream, but it could set you back $9,000 Johnson & Johnson's nasal spray for depression Johnson & Johnson's formulation of esketamine is designed to be taken as a nasal spray alongside a traditional antidepressant, reducing the time required to administer the treatment and potentially making it less expensive. (The company has not said how much the drug could cost.) The company's clinical-trial data suggests that the drug is fairly safe and well tolerated but still has some negative side effects. More than a third of patients in two of Johnson & Johnson's last-phase clinical trials reported dissociation. To address that, researchers say, the drug should be given in the presence of a clinician who can monitor the person for at least two hours after treatment. Roughly a third of patients in the trials reported dizziness, sedation, or nausea. Also, because the studies focused on people with severe forms of depression that don't respond to other medications, suicide was a known risk among the participants. In Johnson & Johnson's trials, at least three patients died by suicide. On Tuesday, experts said these deaths were not likely a direct result of esketamine — if anything, they could have occurred because it didn't work well enough, said Qi Chen, an FDA safety reviewer on the panel. Julie Zito, a pharmacy professor at the University of Maryland who was one of two people who voted against esketamine's effectiveness, said she didn't see enough evidence of substantial improvement in mood among the clinical-trial participants. Other researchers on the FDA panel said the drug still appeared to be more convenient than available antidepressants and the IV version of esketamine because the nasal spray doesn't require an IV and could be given as frequently as once a week. Esketamine also appeared to work better than a placebo in people with severe forms of depression over a month. However, the latest clinical trial — one of five studies presented to the FDA — was not able to show that the drug was statistically superior to a placebo. That's a key finding that other trials appeared to support. For a study published last May, Johnson & Johnson's neuroscience partner, Janssen Research, had nearly 240 adults with severe depression take a traditional antidepressant plus a nasal spray for a month. Half got a spray with Johnson & Johnson's drug, while the other half got a placebo spray. Those results were promising: The people who got the esketamine spray saw significantly better improvements in their depressive symptoms than those who got the placebo. The month before, researchers did a small, daylong version of the study and came away with similar results. But the latest study, of nearly 350 adults, did not show numbers statistically significant enough to bolster the other findings. Nevertheless, most of the experts on the FDA-assembled committee said they considered the drug an effective treatment for severe depression. Some said the latest study still suggested positive results even though the findings didn't reach statistical significance. "I was persuaded not only by the two positive trials but even by the partial evidence in the third trial that was at least pointing in the same direction," Wilson Compton, the deputy director of the National Institute on Drug Abuse with the National Institutes of Health, said on Tuesday.<doc-sep>Together, the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted the benefits of Janssen Pharmaceutical Companies' fast-acting esketamine 28-mg single-use nasal spray outweigh the risks. "The committees based their support on the safety and efficacy data from five Phase 3 studies in patients with treatment-resistant depression: three short-term studies; one maintenance of effect study; and one long-term safety study, according to a Janssen Pharmaceutical Companies press release. And any adverse effects (increased blood pressure, dizziness, dissociative symptoms) "occurred shortly after dosing...were transient...and resolved the same day." The company also proposed a Risk Evaluation and Mitigation Strategy (REMS) to further assess the drug’s effectiveness. » RELATED: One year after teen's suicide, Georgia father continues the fight "The thing I'm most concerned about really is diversion and misuse and things like that," temporary FDA voting member Lee Hoffer of Case Western Reserve University told Medscape. Hoffer has urged the agency to keep a close eye on safety. Esketamine’s fast-acting role spurred by ketamine’s active ingredients is what makes this possible treatment for severe depression most useful, experts say. Unlike other commonly used treatments, which can take several weeks to begin working, esketamine can offer symptom relief more quickly, potentially lowering one’s risk of self-injury or suicide. But ketamine in general has yet to be federally approved, largely because there’s still a lot scientists don’t know. » RELATED: Magic mushrooms for depression? FDA gives treatment 'breakthrough' status According to Medscape, it's still unclear what about ketamine's biology triggers an antidepressant response in one day when most antidepressants usually need two weeks or longer to make an impact. And what does ketamine do to the brain that antidepressants don't do? Still, "well over 3,000" patients in the U.S. and Canada have been treated with ketamine so far, Yale University psychiatry professor Gerard Sanacora told NPR in 2017. When other doctors ask him how he can offer the drug to patients with limited information about its effects, Sanacora responds with this answer: "If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they've tried the standard treatments, how do you not offer this treatment?" When depressed patients who have exhausted their options take ketamine, Sanacora said, 50-75 percent of them feel at least 50 percent better within one day. » RELATED: The suicide rate for teen girls is the highest it's been in 40 years — Is social media to blame? According to the New York Times, despite federal approval, clinics all over the country have began administering intravenous ketamine for depression "as a series of treatments, over a period of days or weeks, and sometimes including follow-up or 'booster' visits months later." Such "off-label" treatments average $3,000 and usually aren't covered by insurance, nor have their effectiveness been thoroughly studied. But if approved, ketamine’s “chemical sibling” esketamine, which would be covered by most insurers, may pave the way for the first new depression treatment in 30 years. The FDA has until March 4 to decide. More about the FDA expert panel meeting at fda.gov.<doc-sep>
An experimental nasal spray, which has a compound similar to the "club drug" ketamine, has been recommended as a new depression treatment by an advisory panel to the Food and Drug Administration Tuesday. The influential panel voted 14-2 in favor of Johnson & Johnson's drug esketamine, a treatment developed to treat major depression in patients who have not benefited from at least two different therapies. The panel said the benefits of the nasal spray outweighed the risks. Side effects include dizziness, nausea and an unpleasant feeling of dissociation, according to the company. One member in the panel abstained from voting. Esketamine is a variation of the anesthetic ketamine, which is also abused as a recreational party drug with the street name Special K. Intravenous infusions of ketamine have been shown to help people with severe depression who experience suicidal thoughts, but the researchers expect that the nasal spray will take effect more quickly and be easier to use. "I think esketamine has the potential to be a game-changer in the treatment of depression ... I use the term potential because the issues of cost and patient accessibility need to be addressed," said Walter Dunn, a panel member who voted in favor of the approval. The nasal spray acts quickly, showing benefits after four hours. The hope is that the spray can help the 30 percent to 40 percent of patients with major depression who don't respond to antidepressants, most of which take at least four weeks to take effect. Currently, Eli Lilly's Symbyax is the only FDA-approved drug for treatment-resistant depression. Major depressive disorder affects over 300 million people globally, and the rate of attempted suicides in people with this condition is about 20-fold higher than that of the general population, according to the company. However, depression is a tricky area of development. Patients in clinical trials often show a big placebo response, masking the efficacy of the drug being tested. The FDA, although not mandated to follow the panel's recommendation, is expected to announce its decision on esketamine by March 4.