Of the 16 million adults in the U.S. who suffer from depression, as many as one-fourth of them receive little or no benefit from the treatment options currently available, including prescription drugs and therapy. This staggeringly high percentage of mental health sufferers represent what might be the most prominent unmet need in American psychiatry. On Tuesday, the FDA (Food and Drug Administration) took a huge step toward meeting the needs of these people by approving the first new mental health medication in over 30 years: a fast-acting drug derived from a well-known and widely used anesthetic, ketamine.
This newly approved antidepressant drug heralds a shift from the Prozac era of mental health drugs. The new treatment, called esketamine and marketed under the brand name Spravato, is a nasal spray developed by Janssen Pharmaceuticals Inc., a branch of Johnson & Johnson. The drug contains an active part of the ketamine molecule, whose antidepressant properties are not well known yet.
“Thank goodness we now have something with a different mechanism of action than previous antidepressants,” Dr. Erick Turner, a former F.D.A. reviewer and associate professor of psychiatry at Oregon Health & Science University, told The New York Times. “But I’m skeptical of the hype because in this world it’s like Lucy holding the football for Charlie Brown: each time we get our hopes up, the football gets pulled away.”
The generic anesthetic is already becoming increasingly available for depression treatment at hundreds of mental health clinics around the country, and studies have suggested that it can help treat depression in treatment-resistant individuals.
The recommended usage of this newly approved drug is twice per week for four weeks, with booster doses administered as needed and used alongside one of the commonly used oral antidepressants. FDA rules mandate that doses be administered in a doctor’s office or mental health clinic, with patients being monitored for at least two hours following administration and their experience with the drug entered into a registry. Patients are also asked not to drive during the day treatment is administered.
Esketamine, like ketamine, has a high potential for abuse, and both drugs have the potential to induce psychotic episodes in individuals who are at high risk for them. The safety monitoring requirements will force doctors and mental health facilities to find space to administer this treatment to patients, which some say could present a logistical challenge.
The cost for one month’s course of treatment will be between $4,720 and $6,785, said Janssen, and experts say that the new drug will give the company a foothold in the $12 billion global antidepressant market, where many drugs are now generic.
Experts say that the approval of esketamine marks a new approach to treating severe mood problems. Prozac and drugs like it enhance the activity of brain messengers such as serotonin. And while they are mildly useful, they can take weeks or months for their effects to be felt, and for many patients, they offer little or no relief from depression symptoms. However, esketamine works within hours, or at most days, and is effective in some people who have not benefited from other antidepressant treatments.
Field experts with experience in treating depression sufferers were encouraged by the news of esketamine but also leary. The effectiveness of the last “new” antidepressant to hit the market was widely exaggerated. And the esketamine trial results, which were paid for and put on by Janssen, were mixed.
In each of the trials submitted, all patients began a course of a new antidepressant drug and were given either a course of esketamine treatment or a placebo. In a month-long study, those who took esketamine performed statistically better than those on a placebo, reducing scores on a standard depression scale by 35 percent, compared to 28 percent for the placebo. However, in two other submitted trials, esketamine did not statistically outperform the placebo. Historically, the FDA has required that a drug succeed in at least two short-term tests before it can be approved; they loosened their criteria for esketamine, opting to instead study relapse rates in individuals who did well on the drug.
In that trial, Janssen reported that only about one-fourth of subjects relapsed, compared to 45 percent of subjects who relapsed after receiving the placebo. All the participants had been given a diagnosis of treatment-resistant depression, having previously failed multiple courses of drug treatment.
For now, esketamine is continuing to be studied carefully, and we’re all waiting nervously to see how it performs long-term and whether or not the side-effects outweigh the potential gains. Only time will tell.