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Depression affects an estimated 300 million people worldwide. And to make matters that much worse, as many as one in five of those people have what's called treatment resistant depression, meaning they don't respond to the usual psychiatric drugs.

But last week, there was renewed hope for them as the US Food and Drug Administration approved a new antidepressant, a kind of ketamine. It represents a whole new class of antidepressant, one that works really quickly and may help the brain fight back long-term. And while it's still being reviewed by other regulatory agencies around the world, getting US approval is a big step.

The nasal spray, marketed as Spravato, contains esketamine, one of the two variants of the psychoactive compound called ketamine. Now, ketamine, or special K as it is sometimes called, is better known as a party drug that causes hallucinations, feelings of happiness, and an “out of body” or dissociative feeling. But it started out as an anesthetic, and there's also been a lot of scientific interest in the drug as an antidepressant.

Several randomized, double blind studies in the 2000s showed that it reduced symptoms of depression like insomnia or feeling hopeless. And as far as we can tell, it works differently than other antidepressants. Though they're not 100% sure what it does, scientists think it blocks particular chemical messengers in the brain that can damage brain cells.

It also seems to help regrow connections between brain cells. That's especially intriguing because, for somewhat unknown reasons, people with depression tend to have fewer of those connections. And from a patient perspective, ketamine starts working a lot faster than traditional treatments.

While things like Prozac can take weeks or months to take effect, ketamine works within hours or days. But, while all of that sounds super promising, some doctors have already expressed concerns. They point out that Spravato didn't exactly do amazingly in its clinical trials, for example.

In one, the drug improved people's symptoms better than a placebo, but in two others, there was no significant difference. That's not usually good enough to get approval from the FDA, but the agency gave the drug special treatment. Also, doctors are understandably nervous that we still don't fully understand how ketamine works, which means we don't know exactly what it does to people's brains.

And it's even less clear what the long term effects of the drug are, so right now, doctors are only prescribing it twice a week for up to four weeks before deciding if patients should continue. Also, there are concerns that esketamine could be misused, so the FDA has set out strict guidelines for administering it, like, it has to be taken in a doctor's office, patients have to be monitored for 2 hours after, and they aren't allowed to drive that day. But, that limits who can receive the drug.

And that's even assuming the people who need it most can afford to take it. A one-month course is projected to cost between 4.5 and 6.5 thousand dollars. That price will drop a little after the first month to 2.5 to 3.5 thousand, the drug company says.

Because that's so much more affordable. Still, it is a major breakthrough in depression treatment because new classes of antidepressants don't come around very often. And this could have really positive effects for millions of people, it just remains to be seen if it actually will.

And speaking of potentially amazing new treatments, two papers published this week in Nature Communications demonstrate that tech already found in doctor's offices could be used to treat a wide range of disorders that are kinda hard to treat right now. The papers used ultrasound, sound waves with frequencies higher than humans can hear, to stimulate nerves, and the results suggest the method could help with inflammatory disorders like some kinds of arthritis or metabolic disorders like high blood sugar. Several previous studies found that electrically stimulating the vagus nerve, which runs down from the brain and branches off to the lungs, heart and digestive system, can dampen the immune response.

Which is important if you're got an over-reactive immune system like people with inflammatory disorders do. You see the vagus nerve is part of the cholinergic anti-inflammatory pathway which, when activated, slows down the production of certain proteins that cause an inflammatory response. But, so far, the best way to stimulate the vagus nerve has been to surgically implant a little electronic device that can just zap it, which doesn't sound nice.

In the studies published this week, scientists tried a different approach, pulsing ultrasound into the spleen, which is connected to the vagus nerve and is a part of that same pathway. In one study, mice were injected with a substance that gives them arthritic symptoms, like swollen ankles and paws. The mice that received ultrasound treatment once a day for a week had less swelling than mice who didn't.

In the second study, the researchers showed that a one-minute pulse of ultrasound to the spleen reduced the amount of inflammatory proteins released after one of those injections, suggesting the ultrasound was acting like an anti-inflammatory. The second study also tried ultrasound on the liver, because it's a big player in regulating the body's metabolism, including things like blood sugar levels. And it turned out a liver ultrasound lowered the rats' high blood sugar.

That is pretty amazing because the rats were only treated with a single, targeted, one minute session of ultrasound. What's more, both spleen and liver ultrasound seem to work just as well as traditional vagus nerve stimulation. So these studies look very promising, though, of course, we have to add the usual caveat about the work being done in mice and rats, who are different from people.

A clinical trial is currently underway to see if this kind of treatment could work for human patients with rheumatoid arthritis, though. The results from that trial are due in May of next year, and if all goes well, ultrasound could become a regular part of treating all sorts of conditions. Patients might even be able to administer their own treatments at home because the machines can be portable.

But like esketamine, there is a lot we don't know and don't understand about what's happening, like how long would someone need to do this ultrasound therapy to keep their symptoms under control. Ultimately, both the FDA approval of esketamine and those ultrasound studies reveal just how much don't know about our own bodies. But, they also show us that promising new treatments for our problematic medical issues are out there, just waiting for creative scientists to find them.

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