March 6, 2019

FDA just approved a fast-acting nasal spray for depression—but it comes with a strong warning

Daily Briefing

    FDA on Tuesday approved a nasal spray antidepressant derived from the anesthetic ketamine to treat adults with severe depression who do not respond to other treatments, the New York Times reports.

    According to Reuters, the drug's approval marks the first time FDA has approved a new type of depression treatment in more than 30 years.

    Background: Ketamine seen as possible treatment for patients who don't respond to antidepressants

    The antidepressants currently on the market in the United States boost the activity of serotonin and other brain messengers, but typically do not begin taking effect for weeks or months, and sometimes do not work for patients with depression. Up to 25% of the 16 million U.S. adults with depression have experienced little to no benefits from using currently available treatment options, such as Prozac, according to the Times.

    As an alternative to traditional antidepressants, hundreds of U.S. clinics have begun treating patients with a course of intravenous ketamine, the Times reports. Research suggests ketamine and ketamine-based compounds can help patients who are resistant to other treatments, according to the Times. Carlos Zarate, chief of the National Institute of Mental Health's experimental therapeutics and pathophysiology branch, said, "What seems remarkable is that the drug … seems to help domains other than depression, like anxiety, suicidal thinking, and anhedonia. It seems to have more broad effects, on many areas of mood."

    In addition, ketamine and ketamine-based compounds can take effect within hours.

    However, ketamine and ketamine-based compounds also have the potential for misuse. Ketamine can lead to psychotic episodes, as well as hallucinogenic and out-of-body sensations. According to the Times, ketamine was a popular club drug, called Special K, in the 1980s and 1990s.

    FDA approves ketamine-based nasal spray antidepressant

    The ketamine-based treatment FDA approved Tuesday, called Spravato, is a fast-acting drug that is absorbed into a patient's blood stream through the nasal passage. FDA approved Spravato, which was developed by Johnson & Johnson's subsidiary Janssen, for use along with an oral antidepressant, Reuters reports.

    According to FDA, a month-long clinical trial showed Spravato performed statistically better than a placebo: Patients who took Spravato along with an oral antidepressant reported a larger reduction in their scores on a standard, 60-point depression scale. Specifically, patients who took Spravato along with the oral antidepressant reported scores reduced by an average of 21 points, while patients who took the placebo reported scores reduced by an average of 17 points. In two other trials, Spravato did not perform statistically better than placebo.

    According to the Times, FDA historically has "required that a drug succeed in two short-term trials before it is approved," but FDA "loosened its criteria for [Spravato], opting instead to study relapse in people who did well on the drug." In the relapse-focused trial, about 25% of patients who took Spravato relapsed, compared with 45% of patients who took a placebo.

    FDA approved the treatment, but only for use in a doctor's office or clinic. FDA acknowledged the drug's potential for misuse and said patients should not be permitted to take Spravato home with them. FDA also said providers must monitor patients who take Spravato for at least two hours after they receive the drug and document patients' experiences in a registry.

    FDA also is requiring Janssen to include a boxed warning on Spravato, which is the strongest type of warning FDA can mandate. The warning will caution providers and patients about the drug's "risk for sedation and difficulty with attention, judgment and thinking, abuse and misuse, and suicidal thoughts," Reuters reports. In addition, FDA has advised that patients should not drive when they have taken Spravato.

    According to NPR's "Shots," Johnson & Johnson has said Spravato's wholesale price will range from $590 to $885, depending on the size of the dose. The company said those prices do not include administration- and observation-related costs, "Shots" reports.

    Reaction

    Experts largely welcomed the drug's approval, but some expressed skepticism, noting that the effectiveness of other antidepressants, such as Prozac and Paxil, "was vastly exaggerated when they came on the market," the Times reports.

    Mathai Mammen, global head of Janssen Research & Development, said, "Spravato has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies."

    Steven Hollon, a professor of psychiatry and behavior sciences at Vanderbilt University, said, "We've had nothing new in 30 years. So if this drug is an effective way to get a more rapid response in people who are treatment resistant, and we can use it safely, then it could be a godsend."

    Erick Turner, a former FDA reviewer and an associate professor of psychiatry at Oregon Health & Science University, also welcomed a new entrant into the depressive drug market. But he said, "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" (Joseph, Reuters, 3/5; Johnson/McGinley, Washington Post, 3/5; Hamilton, "Shots," NPR, 3/5; Carey, New York Times, 3/5).

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