The most controversial antidepressant trial in adolescents gets flagged with an “expression of concern”
STUDY: Keller MB et al, J Am Acad Child Adolesc Psychiatry 2001;40(7):762–772
STUDY TYPE: Expression of concern on a randomized controlled trial
FUNDING: Independent
Background
Study 329 is one of the most controversial trials in psychiatry. Published in 2001, it reported that paroxetine (Paxil) was safe and effective for teens depression — a finding later shown to be the product of selective outcome reporting, ghost-writing, and concealed suicidality data. The original data, reanalyzed in 2015 by the Restoring Invisibile and Abandoned Trials (RIAT) Initiative, showed no benefit with paroxetine in teens and significant harms.
The FDA’s black-box warning on antidepressants and suicidality in youth traces its origins here.
The Update
On April 2, 2026, the journal that published the original study Journal of the American Academy of Child and Adolescent Psychiatry) issued a formal expression of concern about the original 2001 article. I expect more to come.
Practice Implications
- Fluoxetine is the only SSRI with solid FDA-approved efficacy data in teen depression (citalopram, escitalopram, and sertraline are next, but their data is mixed).
- Therapy is first line in teens. Transcranial Magnetic Stimulation (TMS) is newly approved in teens and is safer and more effective than antidepressants.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- Have you seen problems with paroxetine in teens or children?
