The FDA have approved a new medication for hard-to-treat depression.
The Food and Drug Administration (FDA) have just granted approval of the drug esketamine (Spravato) to the Johnson & Johnson company Janssen Pharmaceuticals Inc.
According to its developer, the drug uses the "first new mechanism of action in decades to treat" major depressive disorder.
The aim is that healthcare providers will prescribe the nasal spray to people with major depressive disorder who have tried and received no benefit from at least two antidepressant treatments.
The FDA also say that the drug will only be available through a system of tight distribution and monitoring.
Fast action, different mechanism
One key advantage of the nasal spray is that, because it is fast-acting, it can potentially help those experiencing suicide thoughts more quickly. Traditional antidepressants have a different mechanism of action and can take weeks to start working.
In 2017 in the U.S., there were 1.4 million suicide attempts and 47,173 deaths by suicide.
Esketamine is a form of ketamine, which the FDA approved in 1970. Ketamine has two chemical forms, each being a mirror image of the other. Esketamine comprises just one of these, the "S" form.
The World Health Organization (WHO) list ketamine as an "essential medicine" for use as an injectable, general anesthetic.
Once the user has squirted the spray into their nostril, the lining of the nasal passages will absorb the esketamine from whence it enters the bloodstream. It acts on the N-methyl-D-aspartate receptor in the brain.
Tight restrictions on provision and use
However, because of the risk of serious side effects and "the potential for abuse and misuse of the drug," the FDA have declared that there will be restricted availability and tight monitoring of the drug.
"Because of safety concerns," says Dr. Tiffany Farchione, who works in the FDA's Center for Drug Evaluation and Research, "the drug will only be available through a restricted distribution system, and it must be administered in a certified medical office where the healthcare provider can monitor the patient."
The FDA granted approval following a review of clinical trial results and consultation with external advisors.
A boxed warning on the label will alert users that taking the drug will put them at risk of sedation, dissociation, attention and judgment problems, drug misuse, suicidal thoughts, and suicidal behavior.
People will only be able to use the spray under supervision in the doctor's office or healthcare facility.
The healthcare provider will also have to monitor people for at least 2 hours after each time they use the spray.
People won't be able to take the spray home, and they must sign to say that they will not drive or use heavy machinery for 24 hours.
The drug underwent evaluation in three short randomized trials of 4 weeks and one longer one. The purpose of the longer trial was to test "maintenance-of-effect."
Each short trial tested Spravato against a placebo nasal spray in people who started an oral antidepressant at the start and continued with it through the trial.
In one of the short trials, those taking the active drug showed a statistically significant improvement in depression severity compared with those on placebo. In some cases, the improvement took effect within 2 days.
Neither of the other two short trials met the statistical significance standard required for effectiveness of symptom relief.
In the longer trial, people who had a stable response, or whose remission remained stable, and who continued with the nasal spray and oral antidepressant experienced a statistically significant longer period before relapse compared with those on placebo.
The most common side effects the teams observed in the trials included dizziness, disassociation, sedation, vertigo, nausea, vomiting, anxiety, lethargy, decreased sensitivity, raised blood pressure, and a feeling of intoxication.
Doctors and researchers have been awaiting the news of the drug's approval with mixed views. A recent STAT news report describes reactions as ranging from hesitation to skepticism.
Among the hesitant are those who welcome the fact that, at long last, there is a new drug with a new mechanism. The skeptics, however, are not sure whether there is enough positive data to justify the approval.
Dr. Michael E. Thase, a professor of psychiatry at the University of Pennsylvania in Philadelphia, was the principal site investigator on the clinical trials.
He says, "The impact of depression is greatest for those who do not benefit from standard treatments."
"In phase 3 clinical trials, we saw this therapy provide sustained improvement to patients with treatment-resistant depression."
Dr. Michael E. Thase
Dr. Thase has received research grants from the drug company and worked as a consultant for them.