Psychiatric Drug Approvals Questioned by Researchers

The FDA is often considered the arbiter of new drug approval. Drugs that gain FDA approval are viewed as effective, evidence-based treatments. Yet, in recent years, the FDA has loosened the approval requirements and become embroiled in controversy, approving drugs against the recommendations of its own scientific advisory committees.

Now, researchers have found that recent psychiatric drug approvals follow this same pattern: In a new study investigating 16 FDA approvals for novel psychiatric drugs between 2013 and 2024, researchers found that drugs were approved based on flimsy evidence and against the recommendations of medical reviewers.

For instance, they highlight pimavanserin, an antipsychotic approved in 2016 based on one positive trial out of the four the FDA reviewed. They describe it as “a drug deemed not approvable by the FDA medical reviewers whose decision was overturned by leadership following a favorable advisory committee vote.”

They also highlight gepirone, an antidepressant approved in 2023 based on two positive trials out of the 12 that the FDA reviewed, and describe it as “a drug that was rejected thrice before gaining approval.” Gepirone was first created in 1986 and was a notorious failure for decades before eking out approval.

“The quality of evidence supporting psychiatric drug approvals varied substantially, underscoring the need for increased clarity and consistent application of FDA approval standards among drugs treating mental illnesses,” the researchers write.

The study was conducted by Rosa Y. Ahn-Horst, Erick H. Turner, and Aaron S. Kesselheim and published in JAMA Network Open. The researchers are all involved in the Program on Regulation, Therapeutics, and Law (PORTAL) at Brigham and Women’s Hospital

The current article, a short research letter, doesn’t address the recent controversies in the FDA’s approvals. However, one of the authors—Erick Turner—was a member of the FDA advisory board that considered Janssen’s esketamine drug Spravato. Turner later authored a prominent editorial in Lancet Psychiatry criticizing the FDA’s approval of that drug, calling it “a historic break from precedent.”

In another recent article, Turner and others noted that the FDA’s approval of Spravato provides a prime example of how regulatory bodies have lowered the threshold of evidence for approving these drugs. For decades, the FDA has required at least two well-conducted clinical trials showing that the drug beat placebo. But Spravato failed to demonstrate this. It was approved based on one successful clinical trial despite two others in which it failed to beat placebo. (The FDA accepted a “maintenance” trial as additional evidence of the drug’s success.) Indeed, by the time six efficacy trials were conducted, there was still only one in which the drug beat placebo).

Another recent controversy was the FDA’s approval of Biogen’s Alzheimer’s drug aducanumab (Aduhelm). In 2022, a congressional investigation concluded that the FDA acted inappropriately in approving the drug, citing “serious concerns about FDA’s lapses in protocol” in a process “rife with irregularities.”

The story of aducanumab begins in March 2019, when Biogen’s two Phase 3 trials of the drug were terminated early because they were found to be ineffective and associated with brain bleeding. However, the FDA worked with the drugmaker to find new ways to analyze the data, and two years later, they presented evidence that a small subgroup of patients may have benefited from one of the trials.

The FDA’s advisory board rejected this evidence, voting 10-0 (with 1 “uncertain”) against approving the drug. But the FDA approved the drug anyway. Three advisory board members resigned in protest, and one of them called it “the worst drug approval decision in recent U.S. history.”

The drug was approved not because of evidence that it improved clinical outcomes but because it decreased amyloid in the brain, a controversial surrogate outcome. In fact, researchers have found no evidence that reducing amyloid leads to clinical improvement. Dozens of past medications that targeted amyloid have all failed to improve Alzheimer’s outcomes.

In response to these controversies, researchers have written that “the FDA is failing the American people.”

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Ahn-Horst, R. Y., Turner, E. H., & Kesselheim, A. S. (2025). Characteristics of trials preceding FDA approval of novel psychiatric drugs. JAMA Network Open, 8(1), e2456588. doi:10.1001/jamanetworkopen.2024.56588 [Full text]