Clinical findings like those presented at the December meeting have reinvigorated the field of depression research. “This is really a new generation of drugs for the treatment of depression with a completely different mechanism from the conventional antidepressants,” says Ronald Duman, director of Yale's division of molecular psychiatry. Now, a number of other companies are also working in the ketamine and NMDA receptor research space. Just last month, Janssen Pharmaceuticals, which was already clinically testing new formulations of ketamine, signed a licensing agreement with Germany's Evotec to advance its portfolio of NMDA receptor antagonists.

“I'm encouraged by the fact that we have four or five drugs that all work in somewhat different ways but work through the NMDA receptor,” says Sheldon Preskorn, a psychiatrist at the University of Kansas School of Medicine–Wichita who helped design Naurex's trials. “That gives you a greater level of confidence that where there's smoke, there may be fire.”

Despite the promising results from the newer NMDA receptor–modulating drugs, however, given the more rapid and pronounced effects of ketamine, many psychiatrists aren't ready to write off the older agent quite yet. “For severe depression, sometimes you have to bring out the big guns,” says James Murrough, a psychiatrist at the Mount Sinai School of Medicine in New York.

Murrough recently conducted a randomized trial testing ketamine in 72 people with treatment-resistant depression—the largest such study to date. Notably, that study compared ketamine against midazolam, an antianxiety pill most commonly used to induce relaxation before medical procedures, not saline, as all previous randomized studies have done. Reporting at ACNP, Murrough and his colleagues showed that around 35% of people given ketamine exhibited signs of remission after both one and seven days, compared to 8% and 18% for midazolam at the same time points.

Despite the impressive efficacy data, Sanacora suspects ketamine's days might be numbered. “Ketamine is a drug that requires somebody with quite a bit of experience to administer it and requires some more stringent vital-sign monitoring during infusion. That's going to limit its use,” he says. “The other drugs could easily be given in infusion centers without a tremendous amount of experience. So, if these drugs are equally effective, even if they take a few days more to get to that effect, I think it would be hard to justify using ketamine.”