Feast Drug Antidepressant Receives Support from FDA Advisory Group

SPRING SILVER, Maryland

A form of hallucinogenic party drug, ketamine, has helped lift one of the last barriers to clinical use as an antidepressant.

At a meeting held Feb. 12 at the US Food and Drug Administration (FDA) in Silver Spring, Maryland, an independent advisory group voted 14 to 2 in favor of the recommendation of the US Food and Drug Administration. a compound called esketamine for the treatment of depression. If the FDA approves the drug, it could increase the chances that other ketamine-based treatments are under development. However, the overall effectiveness of esketamine to improve the mood and its potential for abuse remain unresolved.

Mental health researchers have welcomed this news. "I'm still a little shocked," says James Murrough, a psychiatrist at Mount Sinai Hospital in New York. If approved, esketamine would be the first truly innovative antidepressant on the market for several decades. "If that happens, we will have done what people have been quick to point out, which is what has not been done since the original discovery of antidepressants."

The FDA is expected to make a decision on esketamine by March 4.

Mirror image

Researchers discovered the antidepressant properties of ketamine in the early 2000s. It is not known how ketamine, which is a mixture of two molecules that are inverted images of each other, acts in the brain. But scientists know that the drug works very quickly to relieve the symptoms of depression – in hours instead of weeks – and in a very different way from other drugs approved for treating depression.

Ketamine, which can be abused, is already approved for use as anesthetic and can not be patented. Thus, more and more companies are looking for patentable compounds that mimic the structure of ketamine and its apparent effects, such as its speed. Esketamine, manufactured by Johnson & Johnson (J & J) of New Brunswick, New Jersey, contains only one version of the molecules that make up ketamine.

At the FDA Advisory Committee meeting, J & J presented the results of five Phase III trials and several smaller trials of this drug, which included more than 1,700 people. Only two of the five phase III trials were positive and esketamine patients improved only slightly more than those on placebo.

The two FDA panelists who voted against the esketamine approval reported a slight improvement, concerns about the side effects of the drug – including temporary dissociative and hallucinatory effects similar to ketamine – and the risk of drug abuse.

But the majority who voted to recommend the drug to the FDA cited considerations including patient preferences and the likelihood that at least some people will benefit.

"Ketamine is a perverse drug," says Steven Meisel, a member of the advisory board, director of the drug safety system at Fairview Health Services in Woodbury, Minnesota. However, a J & J survey of his participants convinced him that they were willing to risk hallucinations and other side effects because of their so intolerable depression. "We do not consider the voice of patients as often as we should."

Go ahead with caution

Agency officials suggested that if the FDA approves esketamine, it will likely require patients to receive the drug in the health care provider's office, where they will be monitored for approximately two hours. They can also ask J & J to keep a record of who receives it and follow it for years to track their long-term health and to make sure no one resells the drug illegally.

Because so little is known about how ketamine counteracts depression – or its long-term effects – it will take some time before esketamine is used as the first choice treatment. "This is not the next Prozac," says Gerard Sanacora, a psychiatrist at Yale University in New Haven, Connecticut, who has participated in some of J & J's esketamine trials.

But he thinks that this could be an effective treatment now for some people with severe forms of depression. "These people have no hope and now that you offer them hope, this alone is a very powerful tool."