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When Charay Gadd-Spencer thinks of her daughter, she remembers a girl who loved to draw, played soccer year-round in Michigan and dreamed of becoming an Air Force pilot. London Izabella-Ryén Gadd also had a passion for travel and loved taking trips to Mexico with her family.
But in July 2024, London told her mother she needed help with anxiety. Within days, she was prescribed fluoxetine, a selective serotonin reuptake inhibitor (SSRI) commonly known as Prozac. Less than a month later, she took her own life. She was 12.
“We lost her 23 days after being prescribed psychiatric medication,” Gadd-Spencer told The Defender. “I was not told that some children can experience akathisia, emotional blunting, agitation, impulsivity, worsening behavior or sudden suicidal thoughts.”
Her daughter’s death led Gadd-Spencer to question how psychiatric medications are evaluated and approved by the U.S. Food and Drug Administration (FDA) — especially those drugs that are prescribed for children.
“I cannot touch, see, smell, hear or remember anything without thinking of London,” Gadd-Spencer said. “This is a life sentence for our family. I lost my daughter, but I also lost the illusion that something is safe just because it is FDA-approved, prescribed by a doctor or called standard care.”
FDA rejected this SSRI four times — then approved it in 2023
Questions around how antidepressants are approved have resurfaced following a new analysis of the drug Exxua, an SSRI known generically as gepirone.
Researchers writing in JAMA Psychiatry examined the drug’s decades-long regulatory history. They concluded that the FDA-approved labeling emphasizes positive clinical trials — but omits multiple studies that showed the drug wasn’t any more effective than a placebo.
The researchers reviewed 13 efficacy trials submitted to the FDA. They found that only two acute-treatment studies showed positive results, while the majority failed to show the drug was superior to a placebo.
Three studies found the drug statistically inferior to an active comparator — an existing treatment or therapy used as a comparison in a clinical trial.
The FDA rejected Exxua four times, and a 2015 advisory committee voted that efficacy had not been established. Still, the FDA approved the drug in 2023 after agency officials concluded it met the statutory standard for approval.
The study authors said the case illustrates how the FDA may apply “regulatory flexibility,” weighing statistical significance and evidence across trials.
They argued that drug labeling should include all adequate and well-controlled trials, not only those “with positive outcomes, so that clinicians can make better-informed prescribing decisions.”
FDA approved Exxua based on two trials involving 442 adults
According to the FDA, Exxua was approved in September 2023 based on two eight-week, randomized, placebo-controlled clinical trials involving 442 adults with major depressive disorder.
Patients receiving the drug showed greater improvement on the Hamilton Depression Rating Scale compared with placebo.
The FDA said study participants were predominantly women (65%), white (69%), and under age 65 (99%), with 13% identifying as Hispanic or Latino. Safety data were drawn from more than 1,600 patients across additional trials.
The agency concluded that patients treated with Exxua experienced greater improvement in depressive symptoms after eight weeks than those receiving placebo.
The FDA also noted the most common side effects, including dizziness, nausea, insomnia, abdominal pain and dyspepsia (chronic indigestion).
The agency also warned that the drug may increase the risk of QT prolongation, a condition that can lead to sudden cardiac arrest, serotonin syndrome and manic episodes in people with bipolar disorder.
Study: We need to understand regulatory evidence behind novel psych drugs
A separate study published in JAMA Network Open found that the FDA approved 16 novel psychiatric drugs between 2013 and 2024 based on evidence from pivotal clinical trials.
The researchers reviewed regulatory submissions, trial designs and efficacy data to assess the strength of evidence supporting approval decisions.
They noted that psychiatric drug development presents unique challenges because psychiatric diagnoses lack validated biomarkers, and the underlying biology of many conditions remains poorly understood.
The study concluded that understanding the regulatory evidence behind these approvals is increasingly important as novel therapies emerge for depression, psychosis, attention-deficit/hyperactivity disorder (ADHD) and other psychiatric conditions.
FDA approval standards ‘frequently’ allow mixed results
Medical experts interviewed by The Defender said it is not unusual for the FDA to approve medications, even when several clinical trials fail to demonstrate efficacy.
Dr. Josef Witt-Doerring, a psychiatrist and former FDA medical officer, said the agency’s longstanding approval framework “frequently” permits drugs to reach the market despite inconsistent trial results and arguments made by medical professionals.
“Many researchers — including some FDA scientists — have argued that the ‘two positive studies’ standard allows chance findings to play too large a role if numerous other studies are negative,” Witt-Doerring said.
“Under current standards, approval may still be possible if the FDA concludes the positive trials are persuasive and the negative trials are not definitive,” he added.
The FDA generally requires “substantial evidence of effectiveness,” a legal standard that has historically been satisfied through at least two adequate and well-controlled clinical trials demonstrating benefit.
Agency officials, however, evaluate the totality of the evidence rather than relying solely on the number of positive or negative studies.
Patient advocates call for greater transparency
Patient advocates say the approval process should provide physicians and patients with a more complete picture of the evidence.
Kim Witczak, whose husband committed suicide five weeks after being prescribed the antidepressant Zoloft, said, “the system only works when there is complete transparency and truly independent oversight.”
Witczak added:
“The issue is much bigger than any one drug. Clinical trials are designed, funded, managed, analyzed and presented by the sponsor. Pharmaceutical companies are doing what they are designed to do, which is develop products and bring them to market by making the strongest possible case for approval.
“From the company’s perspective, the FDA is the hurdle they must clear to get a product on the market. The FDA’s responsibility is to independently evaluate that evidence and determine whether the benefits outweigh the risks.”
Concerns about selective reporting of antidepressant trials predate Exxua
A landmark 2008 study published in the New England Journal of Medicine compared 74 antidepressant trials registered with the FDA involving more than 12,500 patients with the studies that ultimately appeared in medical journals.
Researchers found that nearly one-third of the trials were never published. Negative or questionable findings were frequently ignored or presented in ways that suggested favorable outcomes.
Among the published literature, 94% of antidepressant trials appeared to report positive results. The FDA’s complete review of the same studies, however, found that only 51% demonstrated positive findings.
The researchers concluded that selective publication inflated the apparent effectiveness of antidepressants by about 32%.
“Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients,” the authors wrote.
An incomplete evidence base can produce “unrealistic estimates of drug effectiveness” and distort the perceived balance between a drug’s benefits and risks, they added.
Critics: Favorable studies more likely to be published than negative findings
Critics of the drug approval process argue that favorable studies continue to receive disproportionate attention while negative findings remain unpublished, underreported or absent from physician-facing materials.
The issue has received particular scrutiny in psychiatry, where treatment outcomes often rely on subjective symptom-rating scales rather than objective biological markers.
Dr. Peter Gøtzsche, professor emeritus, internal medicine specialist and director of the Institute for Scientific Freedom in Copenhagen, has been an outspoken critic of pharmaceutical regulation.
In his 2013 book, “Deadly Medicines and Organised Crime: How Big Pharma has Corrupted Healthcare,” he cites the antidepressant lamotrigine as an example of what he believes is selective reliance on positive evidence.
“Only two positive trials were published for this drug, while seven large, negative trials were not,” he writes. “But the FDA regarded the others as failed trials and approved the failed drug.”
Gøtzsche also argued that the FDA-approved antiepileptic drug pregabalin increases the risk of suicidal behavior, although that conclusion remains disputed within the scientific community.
Dr. Paul Marik, who said he was not familiar with the specific Exuua analysis, nonetheless criticized the broader FDA approval process, calling it “a scientific fraud.”
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‘A drug can be FDA-approved and still devastate a child’
Researchers who analyzed Exxua argue that product labeling should summarize all adequate and well-controlled clinical trials — regardless of outcome — so physicians can evaluate the complete body of evidence instead of a subset of favorable findings.
For psychiatry, where questions about efficacy, placebo response and clinical relevance have shaped debate, the issue addresses how physicians assess risk and benefits, and how much information patients obtain before beginning treatment. It speaks to how regulatory systems deeply impact those seeking care.
For mothers like Gadd-Spencer, the FDA’s method for authorizing psychiatric medications can mean the difference between life and death.
“The FDA approval process has failed families like mine,” she said. “Approval does not mean enough when clinical studies can be shaped, limited, hidden, altered, ghostwriting, presented in ways that benefit drug companies and the system more than the children taking the drugs.”
“Approval does not mean enough when parents are not fully warned, children are not closely monitored, and real-world harms are minimized after the drug is already on the market … a drug can be FDA-approved and still devastate a child,” she added.
The FDA did not respond to The Defender’s requests for comment.
Related articles in The Defender
- 12-Year-Old Died by Suicide 3 Weeks After Starting Prozac, Mother Blames Social Media and Antidepressants
- After Husband’s Suicide, She Wanted Answers About FDA’s Drug Approval Process: ‘It Felt Like Unraveling a Spider’s Web’
- Antidepressants Only 15% Better Than Sugar Pills, FDA Data Show
- FDA Ignored Petition for Labels Warning Popular Antidepressants May Cause Long-term Sexual Dysfunction
- ‘Nobody Told Me’: Former Mental Health Patient Calls Out Dangerous Side Effects of Psychiatric Drugs
