A new analysis finds that Prozac (generic name fluoxetine) is unsafe and ineffective for treating depression in children and adolescents.
Regulatory documents show that trial participants attempted suicide after taking fluoxetine, but these events were excluded from the final journal publication in the Archives of General Psychiatry.Prozac Approval
In 2002, Prozac (fluoxetine), manufactured by Eli Lilly, was FDA-approved for treating depression in children and adolescents based on data from two clinical trials.Both publications reported a small benefit of fluoxetine over placebo in young people with depression, and there appeared to be no significant safety concerns.
Restoring Old Trials
An initiative called Restoring Invisible and Abandoned Trials (RIAT) has enabled researchers to “restore” old clinical trial publications by analyzing documents submitted to drug regulators by drug companies.These analyses have revealed that serious drug harms are underreported or excluded entirely from medical journals.
Dr. Peter Gøtzsche and psychiatrist David Healy obtained regulatory documents (protocols and clinical study reports) from the UK’s drug regulator (MHRA) of the two fluoxetine trials that underpinned the drug’s approval in 2002.
The Discrepancies
Multiple problems were identified when Gøtzsche and Healy compared the clinical study reports of the two fluoxetine trials with those published in the medical journals.Many suicidal events in people taking fluoxetine were either missing or mislabeled in the published reports.
For example, in Study 1, the clinical report described two patients who’d attempted suicide after 12 and 15 days of taking fluoxetine, but these events were excluded from the journal article.
Gøtzsche and Healy found problems with “blinding” in both trials, meaning the trial investigators were likely aware of which patients were on the drug or the placebo.
They also found that people recruited into the trial and who were already taking an antidepressant were only given one week to “wash out” the drug from their systems before commencing the randomization process.
Journals Turn a Blind Eye?
I wrote to both journals asking if the editors would consider correcting the discrepancies and delineating the adverse events not reported in the published articles through an erratum.Neither journal has done so.
The editor at the Archives of General Psychiatry (now called JAMA Psychiatry) rejected concerns about two suicide attempts omitted from its publication of Study 1 and has not made any corrections or clarifications.
In response, Gøtzsche said, “It’s totally unacceptable. When attempted suicides are left out of journal articles, which has happened in many such trials, it changes the safety profile of the drugs completely. This is important information that patients should know about before considering taking the pills.”
Gøtzsche drew similarities to another placebo-controlled trial in adolescents using Paxil (paroxetine).
“A restoration of the data from Study 329 showed that paroxetine was neither safe nor effective for treating depression in children and adolescents,” said Gøtzsche.
“Many suicidal events on paroxetine had been omitted or given an obscure name such as emotional lability. I consider this fraud,” he added.
The editor of the Journal of American Academy of Child and Adolescent Psychiatry (JAACAP), which published Study 2 on fluoxetine, said the journal would not respond to criticisms until the discrepancies documented by Gøtzsche and Healy were published in a peer-reviewed journal.
The process took over a year, but Gøtzsche and Healy’s paper has now been published in a peer-reviewed journal and sent to the JAACAP for review.
“JAACAP takes seriously its responsibility to ensure scientific integrity. As stated in the guide for authors, review of post-publication critiques will be managed according to Committee on Publication Ethics (COPE) guidelines. We will let you know the outcome of the review process.”
Why Does It Matter?
The restoration of old trials has revealed to patients and physicians that much of the data in peer-reviewed journals is incomplete, biased, and often cherry-picked.The exclusion of suicide attempts and suicides distorts the medical literature and prescribing guidelines to the extent that they cannot be trusted. It also may reduce options for safer, more effective interventions such as psychotherapy.
“I’ve heard from many families whose children committed suicide because of antidepressants. We should not be prescribing them to young people,” said Gøtzsche.
Ultimately, it’s the patients who pay the price, sometimes with their lives, from distorted clinical data and from journals that refuse to correct glaring errors.
In conclusion, there seems to be no rationale for using fluoxetine in young people to treat depression. This new analysis concludes the drug is unsafe and ineffective.
Disclosure: I received funding from the RIAT Support Center for publishing two Expressions of Concern in 2021.
Originally published on the author’s Substack, reposted from the Brownstone Institute
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