Johnson & Johnson and Allergan are now testing new drugs for depression that are based on ketamine. There are still safety concerns.

Ketamine, a powerful anesthetic drug, is inspiring scientists and doctors to rethink how we treat depression.

Now, two major pharmaceutical companies, Johnson & Johnson and Allergan, are making strides in developing drugs based on ketamine.

“There’s been a vacuum in the treatment of depression for a good 10 to 15 years. There was the development of the SSRI, and then there was a lot of ‘me too’ drugs. No new mechanisms. Just one more antidepressant after another,” Waguih W. Ishak, professor and vice chairman of psychiatry at Cedars-Sinai in Los Angeles, told Healthline.

Johnson & Johnson is currently in phase III trials of esketamine, which is a mirror image of ketamine’s chemical structure. It’s being developed in a nasal spray formulation.

A representative for Johnson & Johnson told Healthline the company is currently seeking approval for the drug to treat people with treatment-resistant depression and those at imminent risk of suicide.

Treatment-resistant depression is a subset of depression that doesn’t respond to at least two different drug interventions.

Allergan is developing the drug rapastinel. It’s chemically different from ketamine but works in a similar way in the brain.

The company has completed phase II trials for the drug and is expecting the results of their phase III trials next year.

“Rapid-acting therapies have the potential to be game-changing in the treatment of depression, an area where patients are in desperate need of new options. Our studies so far demonstrated rapid onset of efficacy within one day, which lasts days after a single dose and a low potential for abuse,” said David Nicholson, PhD, Allergan executive vice president and chief research and development officer, in a statement to Healthline.

Both esketamine and rapastinel have been granted “breakthrough therapy designation” by the U.S. Food and Drug Administration (FDA).

The designation is a fast-track approval process given to drugs intended to treat a serious condition and that demonstrate substantial improvement over currently available therapies.