Like millions of others, including 23% of American women in their forties and fifties, I have tried selective serotonin reuptake inhibitors (SSRIs)–a class of antidepressant that includes familiar names like Prozac and Paxil. For some people suffering from depression, anxiety, or obsessive-compulsive disorder, these drugs can be miraculous. For most people, they’re just okay (sometimes, barely better than placebo). A lack of efficacy in the severely depressed can mean the difference between life or death.
Even when these antidepressants do work, they have their downsides. The drugs take weeks before they start working–and often require patients to go through weeks of withdrawal when weaning off them. The side effects, like weight gain, headaches, nervousness, and agitation, can force patients to cycle through numerous conventional antidepressants before finding one that has a favorable effectiveness-to-side-effects ratio. In my case, I tried three different drugs before I found one that didn’t cause nightmares or a scarily stiff neck, but none of the drugs were all that effective. Eventually, I got off SSRIs entirely. It just wasn’t worth it.
The worst part of all this: There hasn’t been much new innovation in antidepressants since Prozac was approved in 1987. Until now.
In recent years, psychiatrists have started experimenting with ketamine, a street drug and anesthetic also known as “Special K,” which has shown strong results in treating depression. Ketamine works in a matter of hours, but the psychedelic side effects, which include out-of-body experiences, aren’t conducive to regular use (though the depressed ketamine users quoted by the New York Times seem to enjoy the trippy aspects of the drug).
For now, psychiatrists are using ketamine–an FDA-approved anesthetic–off-label, and there’s no telling when it might be green-lit for treating depression. But a biopharmaceutical company called Naurex thinks it has a better way: two drugs that mimic ketamine’s anti-depressive qualities, without any of the side effects. So far, the clinical trial results look promising.
Both ketamine and Naurex’s drugs, GLYX-13 (intravenous) and NRX-1074 (a pill), work with a receptor in the brain called NDMA, which is associated with everything from depression and anxiety to Alzheimer’s and obsessive-compulsive disorder. About 25 years ago, Naurex’s chief scientific officer, Joseph Moskal, started studying NMDA to understand how it works.
“He found a way of manipulating that receptor, and showed in animal studies that by intervening, you can enhance learning and memory,” says Norbert Riedel, the president and CEO of Naurex. That realization led to Moskal’s discovery that Naurex’s lead molecule, GLYX-13, hits the receptor in a way that causes the symptoms of depression to lessen.
There is an important difference between the way ketamine and Naurex’s molecules interact with the NMDA receptor. Ketamine blocks the NMDA receptor entirely and binds to other receptors as well, causing toxicity and the aforementioned side effects. Riedel says that Naurex’s molecules don’t block the receptor, instead tweaking it to achieve the desired anti-depressant effects.
“The analogy is–if I’m sitting in a room and I say I’m cold, I could set the room on fire, or I could adjust the thermostat,” says Riedel.
For patients, a tweak of the NMDA receptor could mean a fast-acting, side effect-free treatment for depression (and once that’s been proven, anxiety and OCD).
GLYX-13, the injectable drug, went through Phase IIb clinical trials last year, where it was shown to have a meaningful antidepressant effect in the first dose and alleviated patients’ disease after six weeks, achieving either mild depression or remission. Relief from depression occurred in as little as two hours, with no serious side effects reported. It’s designed to be taken at the same time as an an SSRI (and it was, among patients in the trial). The drug, which patients inject using a pre-filled syringe every week or two, still has to go through Phase III clinical trials to further prove its efficacy and safety later this year.
NRX-1074, in contrast, is a first-line therapy that could replace SSRIs for patients–and it can be made into a pill, which is much more convenient. In late January, the drug–a close cousin to GLYX-13–went through its own Phase II clinical trials, showing an antidepressant effect after a single dose (and 24 hours) that’s more than double the effect of other antidepressant drugs after four to six weeks of regular doses.
In other words, it seems to work better, and faster. The big caveat: Patients in the study were given an intravenous form of NRX-1074. Naurex still needs to conduct a trial this year to test the pill version of the drug.
It’s still early days for these antidepressants, and there’s plenty of room yet to fail. As with any drug, there is a chance that long-term side effects will reveal themselves down the line. “There’s a possibility that once it’s used by thousands and millions of people, there could be an unexpected safety signal,” says Riedel.
The two molecules could also fail in their Phase III clinical trials, as many drugs do (in 2013, a ketamine-like antidepressant from pharma company AstraZeneca failed in clinical trials, but the company hasn’t revealed why). Other drug companies, including Johnson & Johnson, are still working on their own ketamine spinoffs.
Armed with $80 million in funding, Naurex has the room to remain independent if it doesn’t want to team up with a big drug company. But it certainly could. “They’re trying to get their arms around it. There’s no shortage of appetite to get these drugs and call them their own,” says Riedel. If ketamine-like drugs really do work better than SSRI’s, there will be no shortage of companies vying for a piece of the profit.