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Chris Gathman, 40, has lived with chronic depression, a condition that runs in his family, for most of his life. He’s used a combination of antidepressants and cognitive behavioral therapy to treat his symptoms, with limited success. In 2018, he sunk into an even deeper depression that began impacting his ability to socialize and complete daily tasks. “I knew I needed to do something,” said Mr. Gathman, who lives in Miami. So when his primary care physician suggested ketamine — an anesthetic that has improved symptoms of depression in early studies — he reached out to a clinic nearby.

HEALTH NEWS Ketamine Is Creating a New Wave of Drugs to Treat Depression Johnson & Johnson and Allergan are now testing new drugs for depression that are based on ketamine. There are still safety concerns. Share on Pinterest Ketamine, a powerful anesthetic drug, is inspiring scientists and doctors to rethink how we treat depression. Now, two major pharmaceutical companies, Johnson & Johnson and Allergan, are making strides in developing drugs based on ketamine. “There’s been a vacuum in the treatment of depression for a good 10 to 15 years. There was the development of the SSRI, and then there was a lot of ‘me too’ drugs. No new mechanisms. Just one more antidepressant after another,” Waguih W. Ishak, professor and vice chairman of psychiatry at Cedars-Sinai in Los Angeles, told Healthline. Johnson & Johnson is currently in phase III trials of esketamine, which is a mirror image of ketamine’s chemical structure. It’s being developed in a nasal spray formulation. A representative for Johnson & Johnson told Healthline the company is currently seeking approval for the drug to treat people with treatment-resistant depression and those at imminent risk of suicide. Treatment-resistant depression is a subset of depression that doesn’t respond to at least two different drug interventions. Allergan is developing the drug rapastinel. It’s chemically different from ketamine but works in a similar way in the brain. The company has completed phase II trials for the drug and is expecting the results of their phase III trials next year. “Rapid-acting therapies have the potential to be game-changing in the treatment of depression, an area where patients are in desperate need of new options. Our studies so far demonstrated rapid onset of efficacy within one day, which lasts days after a single dose and a low potential for abuse,” said David Nicholson, PhD, Allergan executive vice president and chief research and development officer, in a statement to Healthline. Both esketamine and rapastinel have been granted “breakthrough therapy designation” by the U.S. Food and Drug Administration (FDA). The designation is a fast-track approval process given to drugs intended to treat a serious condition and that demonstrate substantial improvement over currently available therapies. The ketamine factor Research into ketamine as a breakthrough treatment for depression has exploded in recent years. Initially developed to treat pain and approved by the FDA in 1970, the drug was first used by U.S. soldiers during the Vietnam War. Scientists didn’t discover the drug’s potential to treat depression for almost 30 years. Researchers began to publish reportsTrusted Source in the year 2000. Since then, interest has only continued to grow. A recurring problem for antidepressants is that they’re slow to act. Most of them take at least two weeks before people feel any of the effects. Ketamine and similar drugs are fast acting, with some people feeling changes in mood within minutes. img-banner - betterhelp_hl_fq_depression_imgbanner_39890 A number of risks However, using ketamine and similar drugs aren’t without risk. In fact, for many years, ketamine has garnered a reputation as a powerful narcotic club drug, capable of rendering users incapacitated. Thus, concerns around ketamine are abundant for both safety, potential misuse, and diversion into the black market. Even when taken therapeutically, people report dissociative symptoms, which can feel like being disconnected from one’s body or the outside world. The drug can also cause hallucinations. “There’s been a lot of concern around oral ketamine, which has been prescribed for people for pain. There is a serious concern for abuse there,” Ishak said. “People take it to get high to get those dissociative feelings and hallucinations if they take higher doses. So, I think that’s definitely a serious concern.” Safety needs to be considered Ketamine and rapastinel are administered through IV infusion. These and esketamine’s nasal formation are only given under supervision. People aren’t simply given a prescription and sent home. The FDA’s final approval of esketamine and rapastinel would have to take serious consideration of the drug’s safety and potential for misuse. Finally, if an orally administered version of any of these drugs were developed, it would also have to prove that it’s both safe and effective. “[These drugs] provide a whole new mechanism of action for antidepressants and a whole new way of administering that. Maybe there are ways to have oral administration become much safer so people can take it conveniently rather than under supervision,” Ishak said. “So, there are a few promising things in it that if they take place, it could easily become a first-line treatment. If this is oral with rapid onset of action, I can tell you this is something I’d prescribe as a first line and not wait until we exhaust two or three trials of other medicines,” he said.

Originally approved by the FDA as an anesthetic in 1970, ketamine is a dissociative drug that can produce visual and auditory distortion as well as dissociation. However, studies have found that with a low dosage, the drug can be used to treat intractable depression. Recently, the FDA approved use of a nasal spray called esketamine as a safe treatment for depression. However, researchers were unsure about the molecular mechanisms of the drug and how it directly affected the brain's response to depression. Many hypothesized the drug increased production of a neurotransmitter called glutamate, but researchers at the Karolinska Institutet in Sweden found the opposite to be true. The study, which was published last week by Molecular Psychiatry, shines a light on the molecular mechanisms that allow ketamine to employ its anti-depressive characteristics. drugs-stock Ketamine, which is used as a medical aesthetic but also as a recreational party drug, could ease the symptoms of depressions, according to a new study. The World Health Organization estimates that more than 264 million people suffer from depression worldwide. GETTY IMAGES NEWSWEEK NEWSLETTER SIGN-UP > The World Health Organization estimates that more than 264 million people suffer from depression worldwide and that close to 800,000 people die due to suicide each year. Of these sufferers, many claim that common treatment does not relieve their depression. The most commonly prescribed anti-depressant is a class of drugs known as SSRIs, or selective serotonin reuptake inhibitors. SSRIs work by increasing the production of serotonin in the brain. Serotonin's primary responsibility is regulating anxiety and stabilizing mood. However, over 30 percent of patients treated with SSRIs experience little to no relief, according to neuroscientist Per Svenningsson from the Karolinska Institutet. ADVERTISING Unlike these common anti-depressants, ketamine directly affects the body's glutamate neurotransmitter, which is closely related to overall mental health. Used as a treatment for depression, ketamine can relieve suicidal thoughts and other symptoms of depression quickly. Using experiments on mice and cells, researchers found ketamine actually reduces activity within the glutamate system, the opposite of what researchers initially believed to be true. "Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine," explained Svenningsson. NEWSWEEK SUBSCRIPTION OFFERS > Researchers also found that ketamine directly affects AMPA receptors which increases the release of a particular neurotransmitter that inhibits glutamate release. This decrease in glutamate happens almost immediately and many treated with ketamine say they feel the results within hours. "These effects could contribute to the efficacy of ketamine to instantly alleviate depressive symptoms and suicidal ideation, taking into account that excessive glutamate levels have been linked to MDD and other mood disorders," according to the study.​​ Now that scientists can explain how ketamine affects the brain, many believe that this will allow for more breakthroughs in depression treatments. "Understanding the mechanisms of ketamine's rapid-onset anti-depressant action may aid the development of novel antidepressant medications that have fewer side effects," the researchers wrote in the study.

A major mental health healing solution is on the horizon: ketamine therapy. A growing body of research shows that the drug, which has long been used as an anesthetic in emergency departments, can be an effective treatment option for several mental health conditions, particularly for people who aren’t getting relief from traditional interventions. It was approved by the FDA last year in nasal spray form for treatment-resistant depression, and many clinics also administer it off-label via IV infusions or dissolvable pills for depression, bipolar disorder, and PTSD. So how does ketamine work? For one, its been shown to boost the function of brain circuits damaged by stress, then later actually repair those circuits, per a study on mice in the journal Science. It can also up the number of serotonin receptors in the brain, found a small Swedish study, making it easier to absorb the “happy” hormone. For 72 percent of the 30 participants, this boost occurred within 24 to 72 hours, which explains why ketamine can provide rapid relief for depression. For the 10 to 30 percent of people with depression and PTSD who don’t respond well to traditional drugs or treatments (mostly women, btw!), options like ketamine offer a new solution. Here, Melanie Lowery shares how ketamine helped her mental health amidst the coronavirus pandemic, and what it's like to do guided ketamine treatments at home.

Seth Wilson, a 41-year-old sommelier in Chicago, has been dealing with depression and anxiety since he was 13 years old. Wilson learned to live with his panic attacks until his mother passed away and they gradually got worse. He had been on some kind of antidepressant or anti-anxiety medication for over a decade, but he wasn’t getting the help he needed. One day last spring, he went to a Field Trip Health clinic overlooking Lake Michigan, put on eyeshades, headphones, leaned back in a comfy zero-gravity leather chair and got an injection of the dissociative anesthetic ketamine. Within seconds he was blasted to the cosmos and entered the event horizon of a black hole.

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