The newly approved drug, esketamine, is one half of the ketamine compound.

By Angela Chen@chengela  Mar 11, 2019, 3:45pm EDTIllustration by Alex Castro/The Verge

For years, ketamine clinics across the country have offered intravenous infusions as a fast-acting treatment for severe depression. But last week, the US Food and Drug Administration approved a version of ketamine, called esketamine, to do the same thing — so what’s the difference and what will this mean for newly interested patients?

Ketamine, sometimes known as the party drug Special K, is a compound made of two mirror-image molecules. It has long been approved as an anesthetic, isn’t covered by a patent, and is widely used — meaning it’s not going to make much money for a pharmaceutical company. So, Janssen patented the left part of the molecule, esketamine, and sent it through the FDA approval system as a potential cash cow called Spravato, legitimizing the use of ketamine for depression in the process.

“We deliver an off-label treatment that has the baggage of being known as a club drug,” says Steve Levine, the founder of Actify Neurotherapies, which runs 10 ketamine clinics around the country. “Now we’ve moved from ‘we deliver horse tranquilizer off-label’ to ‘we deliver FDA-approved Spravato’ and it’s just easier to talk to people about that.”“THIS DRUG WAS SCORNED BY ALL THE BIG COMPANIES UNTIL THEY COULD FIND A WAY TO GET A PIECE OF THE ACTION”

Still, FDA approval of esketamine for treating depression comes with plenty of caveats. The drug must be administered as a nasal spray, patients must be taking another antidepressant at the same time, and it can only be given to patients who have (unsuccessfully) tried two antidepressants before. Most notably, people won’t able to pick up Spravato at the local Rite Aid. Spravato will only be available in certified clinics.

Though Janssen, the maker of Spravato, has yet to officially announce what “certification” means, some psychiatrists have a head start on the process. Lori Calabrese, a psychiatrist who offers ketamine treatments at her clinic in Connecticut, is already certified because she contacted Janssen as soon as news of the approval went through. She had to go through a risk evaluation and mitigation strategy (REMS) program, which meant providing verification of all her medical licenses and showing that her clinic has been approved by the Drug Enforcement Administration for dispensing controlled substances. The next day, Calabrese was notified that she is cleared to administer Spravato. (A representative from Janssen was not available for comment.)

Doctors must order medication for a particular patient and pick it up at a specialty pharmacy. The patient will self-administer the nasal spray in the doctor’s office, stay in the office for two hours of monitoring, and then be taken home. The Spravato never leaves the facility. “It’s a very different kind of treatment model than anything we’ve seen in psychiatry before,” Calabrese adds. Janssen has told her that the first shipments of Spravato will be sent out on March 18th.

Plenty of excitement has greeted the Spravato news, but physicians caution that the requirement that it be taken nasally — instead of through IV, which is the typical method in clinics — may make it less effective. With an IV, all of the medicine is absorbed and the delivery is far more controlled, says Levine of Actify Neurotherapies. Though the nasal spray will help people who can’t (or don’t want to) take an IV, the process might be a little clunkier, especially because some of the drug might drift down people’s throats and it’s harder to control how much someone will get. There is also some evidence that nasal ketamine will be less effective than IV ketamine. Some studies have shown that more than 70 percent of those who try IV ketamine feel better; that number is closer to 45 percent for nasal ketamine.

It’s not cheap, either. Ketamine treatments usually cost a few hundred dollars per infusion, but the expense comes not from the generic drug, which is cheap, but from the doctors’ time and the clinic space. In contrast, just the Spravato drug alone can cost almost $900 per session, which would bring a monthly cost — at the recommended two sessions a week —to nearly $7,000, according to Stat News. The good news is that Spravato will be reimbursed at least partly by insurance, which will greatly increase access, says Bryan Clifton, chief medical officer of Kalypso Wellness Centers, another ketamine clinic. But as Calabrese points out, it’s going to be a challenge to figure out how much of the time and labor costs insurance will cover when the treatment alone is more expensive than the alternative, which already has those costs factored in.

For some, the approval of Spravato is more a story about the failures of the medical industry than great news about an exciting new treatment. “We’re very happy to see ketamine mainstream, but I’m distressed that this commodity medicine that’s so freely available got no interest until somebody could find a way to make more money from it,” says Steven Mandel, who runs Ketamine Clinics of Los Angeles. “It’s so thrilling to see this treatment endorsed publicly by mainstream institutions, but it’s one of the worst aspects of our medical system that this drug was scorned by all the big companies until they could find a way to get a piece of the action.”

Erik Messamore, a professor of psychiatry at Northeast Ohio Medical University, agrees. Messamore — who used to work with patients with treatment-resistant depression — wanted to administer ketamine for a patient, but was told that his insurance carrier would not protect him from liability because the drug was not FDA approved. We didn’t need esketamine, he argues. We needed channels for regular ketamine to be accepted in clinical practice. He maintains that instead of waiting for Janssen’s clinical trials, it would have been more helpful if the American Psychiatric Association, the National Institutes of Health, or another official board released guidelines that encouraged the use of ketamine for this kind of treatment.

That said, Messamore adds that if he were still working with severely depressed patients, he would absolutely offer Spravato. “I would be pressing my administration to get it offered to people as quickly as possible,” he says.

[Read the Original Article]