High hopes and hype for ketamine, an experimental drug against depression



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Teresa Crawford / AP

Lauren Pestikas holds her dog Sambuca in Chicago on August 1, 2018. Since the start of ketamine infusion treatments, she feels much better for a few weeks after each session. His monthly infusions last about 45 minutes and cost $ 550 each. Pestikas battled depression and anxiety and made several suicide attempts before starting ketamine treatments earlier in the year.

CHICAGO – It was launched several decades ago as an anesthetic for animals and humans. He became a powerful painkiller on the battlefield in Vietnam and evolved to become the drug of Special K trippling club.

The chameleon drug, ketamine, is finding new life as an unapproved treatment for depression and suicidal behavior. In the United States, clinics have opened by promising immediate relief with their "single" doses of ketamine in intravenous infusions, aerosols or pills. And desperate patients spend thousands of dollars for treatment often not covered by health insurance, with little evidence on the benefits and long-term risks.

Chicago preschool teacher Lauren Pestikas has long battled depression and anxiety and made several suicide attempts before trying ketamine earlier this year.

Until now, the price is about $ 3,000, but "it's worth it," said the 36-year-old.

Pestikas said that she felt much better for a few weeks after each treatment, but the effects fade and she struggles to find a way to pay for another.

For now, Ketamine has not been approved by the US Food and Drug Administration to treat depression, although doctors can use it for this purpose.

Ketamine has existed since the 1960s and is widely used as anesthesia drug during a surgical procedure because it does not suppress breathing. Compared with opioids such as morphine, ketamine is not addictive and does not cause breathing problems. And some studies have shown that ketamine can relieve symptoms within hours in the most severe cases.

Its potential effects on depression have been discovered in animal experiments conducted in the late 1980s and early 1990s, showing that glutamate, a chemical messenger of the brain, may play a role in depression. and that drugs, including ketamine, that target the glutamate pathway, may act as antidepressants.

Conventional antidepressants, such as Prozac, target serotonin, a different chemical messenger, and usually take weeks to months to go off, which can cause severely depressed patients to fall into despair.

The potential of ketamine for almost immediate relief if temporary is what makes it so exciting, said Dr. Jennifer Vande Voort, a psychiatrist at the Mayo Clinic who treats patients with depression since February.

"We do not have a lot of things that produce this kind of effect.What worries me is that it's so excited," she said. .

The strongest studies suggest that it is more useful and generally safe to provide short-term help to patients who have not benefited from antidepressants. That's about one-third of the world's estimated 300 million people with depression.

"This has really revolutionized the field," has changed scientists' view of the effects of depression on the brain and shows that rapid relief is possible, said the Yale University psychiatrist. Gerard Sanacora, who has been researching or consulting companies seeking to develop ketamine. based drugs.

But to become a standard treatment for depression, he said, there is still much to be done.

Last year, Sanacora co-authored a report of the American Psychiatric Association's Task Force on Ketamine Treatment for Mood Disorders, highlighting the benefits, but highlighting that "major shortcomings "persist in knowledge about long-term efficiency and safety. Most studies have been modest, conducted in research contexts and not in the real world.

When administered intravenously, ketamine can cause a rapid increase in heart rate and blood pressure, which can be dangerous for some patients. Ketamine can also cause hallucinations that some patients find scary.

"There are real concerns," said Sanacora. "We know that this drug can be abused, so we must be very careful about how it is developed."

Dr. Rahul Khare, a specialist in emergency medicine in Chicago, discovered for the first time, a decade ago, the other potential benefits of ketamine from a depressed and anxious patient that he was preparing to calm down to repair a dislocated shoulder several times.

"He said 'Doc, give me what I had last time, for about three weeks I felt a lot better,'" recalls Khare.

Khare became intrigued and earlier this year he began to offer ketamine for the treatment of severe depression at an outpatient clinic that he opened a few years ago. He also joined the American Society for Ketamine Physicians, created a year ago, representing about 140 doctors, nurses, psychologists and other Americans, using ketamine for depression or other unapproved uses.

There are about 150 ketamine clinics in the United States, up from about 20 three years ago, said Dr. Megan Oxley, co-founder of the company.

Khare said that the burgeoning field "is like a new frontier" where doctors meet at meetings and compare notes. He treated about 50 patients with depression, including Pestikas. They are usually desperate for relief after failing to respond to other antidepressants. Some have lost their jobs and relationships because of severe depression, and most find that ketamine allows them to function, Khare said.

The typical treatment at his clinic includes six 45-minute sessions over approximately two weeks, at a cost of $ 550 each. Some insurers will pay about half of it, covering the cost of visiting Khare's office. Patients may receive "booster" treatments. They must sign a four-page consent form stating that the benefits may not be sustainable, listing potential side effects and in bold, the treatment is not approved by the government.

At a recent session, the seventh of Pestikas, she sits against a reclining white chair, while a nurse connected her to a heart monitor and a blood pressure monitor. She grimaced when a needle slipped into the palm of her left hand. Khare raised her hand with a syringe to inject a small dose of ketamine into an infusion bag hanging over the chair, then lowered the light, pulled the curtains out of the window and asked if she had any questions and if she felt well.

"No questions, just grateful," Pestikas replied with a smile.

Pestikas listened to music on his iPhone and watched psychedelic videos. She said it was like "a controlled acid trip" with pleasant hallucinations. The trip ends shortly after the withdrawal of the infusion, but Pestikas said that she felt calm and relaxed the rest of the day and that the mood rush could last for weeks.

Studies suggest that a single intravenous dose of ketamine much smaller than that used for sedation or feasting can help many patients get relief in about four hours and for nearly a week.

The exact functioning of ketamine is not clear, but one idea is that, by increasing glutamate levels, ketamine helps nerve cells restore connections that were invalidated by depression, said Dr. Carlos Zarate , expert in ketamine, head of experimental therapies at the National Institute of Mental Health. .

A small study from Stanford University published in August suggests that ketamine can help relieve depression by activating opioid receptors in the brain.

Janssen Pharmaceuticals and Allergan are among the pharmaceutical companies developing ketamine-like drugs for depression. Janssen is leading the effort with his esketamine nasal spray. The company filed a new drug application in September.

Meanwhile, dozens of studies are underway to try to address some of the unknowns of ketamine, including whether repeat IV treatments are more effective against depression and whether it is possible to determine precisely which patients are most likely to benefit.

Until there are answers, Zarate from the Mental Health Institute said that ketamine should be a treatment of last resort for depression after failure. other methods.

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