The Food and Drug Administration’s recent approvalTrusted Source of a novel drug to treat depression called esketamine (Spravato) has been hailed as a breakthrough by experts in the field of mental health.
For others, questions and concerns still remain.
Spravato, developed by Janssen Pharmaceuticals, is a nasal spray for treatment-resistant depression that was given “breakthrough therapy designation” by the Food and Drug Administration (FDA) in 2016.
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.
Esketamine is fast acting, showing improvement in depression symptoms in patients in as little as 24 hours after the first dose. It also represents the first new mechanism of action in an antidepressant in decades — meaning that it works differently from traditional antidepressants like SSRIs.
But the promise and excitement of the drug have been met with controversy.
Esketamine is chemically nearly identical to ketamine, a powerful anesthetic that, over the years, has garnered a reputation as a powerful narcotic club drug.
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A new report from Kaiser Health News alleges that the FDA, under pressure to green-light potentially lifesaving drugs, may have overlooked certain risks posed by esketamine to users.
The report also claims that clinical data of esketamine effectiveness was only modest and that the FDA did not follow its own precedents for which clinical trials it would accept during evaluation.
According to reporting by KHN, Dr. Jess Fiedorowicz, a member of the FDA advisory committee that reviewed the drug, described its benefit as “almost certainly exaggerated.”
Most egregious, the author argues that three suicides among people using Spravato during clinical trials, compared with no suicides in the control group, were “dismissed” by the FDA.
The FDA has addressed the suicidesTrusted Source, noting “it is difficult to consider these deaths as drug-related.”
Both the FDA and Janssen reiterated to Healthline that they stand by the safety and efficacy of the product, as well as the approval process.
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition. Controlled clinical trials that studied the safety and efficacy Spravato, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment,” said an FDA spokesperson in an email to Healthline.
In an editorial published last month in the New England Journal of Medicine, FDA authors explained the agency’s rationale for approving the drug and their approval process in general.
Two of the four studies reviewed by the FDA did not show a statistically significant treatment effect. However, as part of their reasoning, the FDA authors pointed out that this is relatively common among studies on antidepression medication.
“Our experience has been that approximately 50% of short-term,
randomized, controlled trials for approved antidepressants may still
fail to show a statistically significant effect,” the authors wrote. “For esketamine, the positive short-term trial and the positive randomized withdrawal trial provided substantial evidence of effectiveness.”
They also mentioned there are safety concerns including abuse potential. However they said implementing a Risk Evaluation and Mitigation Strategy (REMS)Trusted Source — including the fact that the drug can only be given in a supervised doctor’s office — can help balance the need for new therapies and patient safety.
“The intent of the REMS is to mitigate the risk of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, while providing access to this effective treatment for treatment-resistant depression,” they wrote.
Many of the concerns raised by KHN have also been raised by Dr. Alan F. Schatzberg, Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine who wrote an editorial last month in the American Journal of Psychiatry.
Those concerns, include questions about esketamine’s efficacy, dosing, and potential for withdrawal.
Schatzberg recently told Healthline that when it comes to esketamine, “We’re headed into uncharted waters.”
A representative for Janssen refuted much of the criticism raised by KHN and Schatzberg.
Dr. David Hough, compound development team leader for esketamine, who oversees the clinical development of Spravato at Janssen Pharmaceuticals, told Healthline they were focused on patient safety.
“We feel very confident that we have done everything to ensure patient safety in this program,” Hough told Healthline. “We’ve been studying this product now for seven years. We have an enormous investment in resources and time and we’ve done 28 different studies to demonstrate that this product works in over 1,700 patients.”
“I don’t know why people want to pick and choose and cherry pick negative pieces of information and collect them together and say that FDA didn’t do a good job. I disagree with that. I think that’s false,” Hough added.