Johnson & Johnson, one of the pharmaceutical companies pursuing the drug’s fast-acting antidepressant qualities, presented some promising new research on Saturday that could raise the drug’s profile as a potential treatment for the condition.
It’s a dramatic departure for a compound that most people know either as a surgical anesthetic or a party drug. And it’s a seemingly welcome one, according to physicians and psychiatrists who say they’ve grown tired of giving patients the same mediocre drugs for the past four decades.
Johnson & Johnson isn’t the only drugmaker that’s hot on the ketamine trail. Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine, and San Francisco drugmaker VistaGen is studying a similar ketamine-inspired drug.
J&J’s version of ketamine is a nasal spray made with a compound called esketamine, the chemical mirror image of ketamine. In its latest clinical trial, the company’s neuroscience partner, Janssen Research, wanted to show that the spray was safe, well tolerated, and superior to both a placebo and a traditional antidepressant.
To do it, the researchers had 236 adults with treatment resistant depression — known as one of the hardest forms to treat — take a traditional antidepressant for four weeks alongside a nasal spray. Only half of them got a spray with J&J’s drug in it; the other half got a placebo.
Their results were promising: The people who got the real spray saw significantly better improvements in their depressive symptoms than those who got the placebo, over the course of 28 days. More importantly, it is also the first time a novel treatment has come out on top even when compared to a traditional antidepressant drug.
The findings come roughly a month after J&J published the results of a small, preliminary version of this study which suggested that over the course of a single day, the spray and traditional antidepressant combo was better than a placebo and traditional antidepressant combo. That study, however, suggested the results diminished over the course of four weeks, while the longer and larger study suggests they might not.
The emerging science on ketamine
Depression is one of the world’s leading causes of death. Current treatments for depression, which take roughly five weeks to begin to take effect, may not work well in up to 80% of the people who get them.
Most existing antidepressants, from Abilify to Zoloft, work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in mood. The result is more free-floating serotonin and, in some people, relief from a dark curtain of depressive symptoms.
Ketamine doesn’t work this way. It capitalizes on a different mechanism in the brain and affects key switches called NMDA receptors.
Like serotonin receptors, those for NMDA play an important role in our mood and help keep our emotions in check. But NMDA receptors also keep our brain’s synapses — the delicate branches that serve as the ecosystem for our thoughts — flexible and resilient.
Potentially because of depression’s damaging effects on these brain switches, it appears to cause our synaptic branches to shrivel up and in some cases even to die. Scientists think existing antidepressants send help to those branches indirectly over time by way of serotonin. Ketamine, by contrast, delivers its aid directly to the source, plugging up NMDA receptors like a cork in a bottle, and nipping depressive symptoms within hours.
A 2012 study published in the journal Science analyzed ketamine’s rapid ability to reduce depressive symptoms in people who’d failed to respond to other drugs. The authors called ketamine “the most important discovery in half a century.” Five years later, researchers concluded in a study in the American Journal of Psychiatry that the drug’s antidepressant effects appeared to last at least a month.
Still, like any drug, ketamine has a range of unpleasant side effects, the most troublesome of which appears to be its tendency to produce what are known as dissociative, or “out of body,” experiences.
Experts worry those effects could lead patients to either react negatively to the experience and not want to repeat it, or react positively and want to repeatedly use, potentially leading to a drug-use disorder.
In J&J’s most recent study, patients reported other side effects as well, including dizziness, headache, blurred vision, and nausea.
The biggest unanswered question: long-term effects
Besides its immediate side-effects, some researchers approach ketamine with hopeful caution for another reason.
Without a good number of long term studies on ketamine for depression, it’s tough to know what the drug’s effects might look like over the course of several months or years. Its beneficial effects, for example, could wear off; other negative side effects could emerge as well.
Allergan and VistaGen are currently doing long term studies of their new drug candidates, which act on the same pathway as ketamine but appear to have substantially fewer side effects; results from those trials are expected in the next two years.
J&J is also pursuing more research on its nasal spray ketamine formula, some of which will include longer trials. Company representatives told Business Insider that in addition to the research they’ve presented so far, they also have plans to study the nasal spray formula in teens with major depression who are at imminent risk for suicide.
The company is expecting to file for approval of their drug with the US Food and Drug Administration later this year.