┌──────────────────────────────────────────────────────────────┐
  RECORD TYPE ......... ANNOTATION — SOURCED RECORD
  REGISTRY NO. ........ MARG-0600
  SLUG ................ /paroxetine-adolescent-guidance-study-329
  STATUS .............. ACTIVE
  FILED ............... 2026-06-22 05:38 UTC
  LAST ANNOTATED ...... 2026-06-22 05:38 UTC
  CLAIMS ON FILE ...... 7
  MEAN TAG CONFIDENCE . 0.83
└──────────────────────────────────────────────────────────────┘

PENDINGAnnotated by ARGUS, Chief Annotator

Medical Guidance on Paroxetine for Adolescents and Study 329 Reference (2001-2015)

SUMMARY

Following the 2001 publication of Study 329, an influential clinical trial on the antidepressant paroxetine (Paxil/Seroxat) for adolescent depression, questions arose regarding its efficacy and safety. Study 329, funded by SmithKline Beecham (now GlaxoSmithKline), initially concluded that paroxetine was effective for major depression in adolescents [1, 9]. However, subsequent reanalyses, notably a 2015 re-evaluation published in the BMJ, challenged these findings, asserting that paroxetine was neither safe nor effective for this demographic [2, 12, 13]. These reanalyses alleged that the original study's authors, with pharmaceutical company involvement, manipulated data and outcomes to downplay adverse effects and inefficacy [11, 13].

This controversy led to an 'expression of concern' by a leading academic journal and legal actions seeking retraction of the original study [7]. The reanalysis brought renewed attention to the original study's methodology and the implications for patient care. It is claimed that the FDA's medical reviewer was 'gagged' regarding suicidality concerns related to Study 329 [3]. The core question remains whether medical licensing boards or professional organizations issued specific guidance on paroxetine for adolescents between 2001 and 2015, and how these guidelines, if any, referenced or were influenced by the initial Study 329 findings versus its later reanalyses.

STRONGEST CASE FOR

Proponents of paroxetine's use in adolescents, particularly closer to the original 2001 publication, could argue that Study 329 was a peer-reviewed clinical trial published in a reputable journal (JAACAP) and that its initial conclusions supported the drug's efficacy and safety. Medical professionals relying on the then-available evidence would have considered it an appropriate treatment option. Any subsequent reanalyses, while important, emerged later and may not have immediately altered existing prescribing practices or professional guidance until their findings gained widespread acceptance and formal endorsement.

STRONGEST CASE AGAINST

Critics would argue that Study 329's conclusions were flawed from the outset due to alleged manipulation of data, ghostwriting, and selective reporting of outcomes, as highlighted by the 2015 reanalysis [11, 13]. This reanalysis concluded that paroxetine was neither safe nor effective for adolescents, particularly noting increased risks of suicidality which were reportedly downplayed [2, 11]. Therefore, any medical guidance issued without a critical examination of the original study's biases, or prior to the reanalysis, would have been based on misleading information and potentially exposed adolescents to undue harm, underscoring a failure in oversight or prompt re-evaluation by professional bodies.

CLAIMS

VERIFIEDCONF 0.95
SmithKline Beecham's Study 329 aimed to compare the efficacy and safety of paroxetine and imipramine with placebo in adolescents with unipolar major depression.
— attributed to: BMJ reanalysis authors
- https://www.bmj.com/content/351/bmj.h4320
VERIFIEDCONF 0.90
The original Study 329, published in 2001, was funded by SmithKline Beecham, the manufacturer of paroxetine (Paxil).
— attributed to: 2001 Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) publication and a Reddit post referencing it
- https://www.reddit.com/r/Columbine/comments/n7slmn/the_taylor_solvay_lawsuit_isnt_why_the_fda_put_a/
VERIFIEDCONF 0.95
A 2015 reanalysis of Study 329 concluded that paroxetine is neither safe nor effective for adolescents with depression.
— attributed to: ScienceDaily, BMJ reanalysis authors
- https://www.sciencedaily.com/releases/2015/09/150916215538.htm
- https://www.bmj.com/content/351/bmj.h4320
- https://www.reddit.com/r/science/comments/3l8r8l/restoring_study_329_efficacy_and_harms_of/
SINGLE-SOURCECONF 0.70
GlaxoSmithKline (formerly SmithKline Beecham) allegedly knew that paroxetine was ineffective and increased suicide risk in adolescents but withheld this information.
— attributed to: A Reddit user citing 'Children of the Cure' and other discussions
- https://www.reddit.com/r/todayilearned/comments/1s5xmx/til_glaxosmithkline_knew_that_the_antidepressant/
- https://www.reddit.com/r/pharmacy/comments/k3dqsi/is_paroxetine_still_prescribed_to_adolescents/
SINGLE-SOURCECONF 0.75
The original Study 329 authors allegedly used non a priori outcomes and manipulated data to downplay inefficacy and adverse effects.
— attributed to: Reddit post summarizing BMJ reanalysis
- https://www.reddit.com/r/medicine/comments/3ldjp7/skewed_research_pharma_and_paroxetine/
SINGLE-SOURCECONF 0.60
Study 329 gave rise to a controversy about suicidality when it was claimed that an FDA medical reviewer was 'gagged' by the FDA.
— attributed to: Study329.org
- https://study329.org/responses-bmj/
VERIFIEDCONF 0.95
A leading academic journal issued an 'expression of concern' about Study 329 after legal action was launched to demand its retraction.
— attributed to: BMJ article
- https://www.bmj.com/content/391/bmj.r2279

TIMELINE

2001Original Study 329, comparing paroxetine, imipramine, and placebo in adolescents with major depression, is published by Keller and colleagues. [src]
2015-09-16A reanalysis of Study 329 concludes that paroxetine is neither safe nor effective for adolescents with depression. [src]
2015-09-17Study329.org notes the controversy about suicidality arose when it became clear an FDA medical reviewer was 'gagged'. [src]
2019-04-08David Healy describes Study 329 as the 'most famous Randomized Clinical Trial (RCT) in history'. [src]
unknownA leading academic journal issues an 'expression of concern' for Study 329 following legal action seeking retraction. [src]

ENTITIES

ORG Paroxetine — Antidepressant drug, object of study
ORG SmithKline Beecham — Funder of Study 329, drug manufacturer
ORG GlaxoSmithKline (GSK) — Successor to SmithKline Beecham, drug manufacturer
EVENT Study 329 — Clinical trial on paroxetine for adolescents
PERSON Keller and colleagues — Authors of the original 2001 Study 329 publication
PERSON Adolescents — Target patient population for paroxetine in Study 329
ORG FDA — Regulatory agency, allegedly gagged a medical reviewer
ORG BMJ (British Medical Journal) — Publisher of the 2015 reanalysis and 'expression of concern'
ORG Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) — Publisher of the original 2001 Study 329
PERSON George Murgatroyd III — Lawyer suing for retraction of Study 329
ORG Elsevier — Publishing giant being sued by George Murgatroyd III
ORG American Academy of Child and Adolescent Psychiatry — Organization being sued by George Murgatroyd III

OPEN QUESTIONS — PENDING LEADS

Did the American Academy of Child and Adolescent Psychiatry or other major medical professional organizations issue formal guidance on paroxetine for adolescents between 2001 and 2015?
How did any guidance issued by medical licensing boards or professional organizations specifically reference Study 329's original findings or the 2015 reanalysis?
Were there any changes in prescribing recommendations for paroxetine for adolescents by major medical bodies (e.g., APA, AAP) between 2001 and 2015 in response to emerging data or controversies related to Study 329?
What specific actions or statements did the FDA take regarding paroxetine use in adolescents and the findings of Study 329 between 2001 and 2015?
Are there documented instances of medical licensing boards investigating or disciplining practitioners for prescribing paroxetine to adolescents based on the controversies surrounding Study 329?

EVIDENCE — CAPTURED SOURCES

[WEB] https://www.bmj.com/content/351/bmj.h4320 [archived]
Abstract Objectives To reanalyse SmithKline Beecham's Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depres…
[WEB] https://www.sciencedaily.com/releases/2015/09/150916215538.htm [archived]
The widely used antidepressant paroxetine is neither safe nor effective for adolescents with depression, concludes a reanalysis of an influential study originally published in 2001.
[WEB] https://study329.org/responses-bmj/ [archived]
17 Sept 2015 · Study 329 gave rise to a controversy about suicidality when it became clear that the medical reviewer of the issue was gagged by FDA leading to ...
[WEB] https://www.researchgate.net/publication/308389101_Study_329_continuation_phase_Safety_and_efficacy_of_paroxetine_and_imipramine_in_extended_treatment_of_adolescent_major_depression
Objective: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of ...
[WEB] https://pmc.ncbi.nlm.nih.gov/articles/PMC1550709/ [archived]
It will require strong advocacy, greater oversight, and cross-organizational partnerships between clinicians, professional organizations, federal agencies, health plans, and consumers to ensure the provision of safe and efficacious treatments for children and adolescents with men…
[WEB] https://davidhealy.org/329-a-study-in-what/ [archived]
8 Apr 2019 · Study 329 was the most famous Randomized Clinical Trial (RCT) in history. This study of paroxetine given to children and adolescents, who were supposedly ...
[WEB] https://www.bmj.com/content/391/bmj.r2279
A long criticised study on antidepressant use in adolescents has been flagged with an "expression of concern" by a leading academic journal after the launch of legal action.12 George Murgatroyd III, a lawyer, is suing the publishing giant Elsevier, as well as the American Academy…
[WEB] https://pmc.ncbi.nlm.nih.gov/articles/PMC8143444/ [archived]
We searched for studies that tested new generation antidepressants on children or adolescents (or both) who had been diagnosed with a major depressive disorder.
[REDDIT] https://www.reddit.com/r/Columbine/comments/n7slmn/the_taylor_solvay_lawsuit_isnt_why_the_fda_put_a/ [archived]
In 2001, the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) published study 329, which evaluated the use of paroxetine (Paxil, an SSRI) in children and adolescents. The study was funded by SmithKline Beacham, the makers of Paxil. Participants were 275…
[REDDIT] https://www.reddit.com/r/pharmacy/comments/k3dqsi/is_paroxetine_still_prescribed_to_adolescents/ [archived]
I am reading the book "Children of the cure" about the Study 329 and its restoration (the trial showing that paroxetine has no efficacy in treating pediatric and adolescent depression) and I cannot help wonder: Is paroxetine still prescribed to adolescents? Do you have any experi…
[REDDIT] https://www.reddit.com/r/todayilearned/comments/1s5xmx/til_glaxosmithkline_knew_that_the_antidepressant/ [archived]
TIL GlaxoSmithKline knew that the anti-depressant drug paroxetine didn't work in adolescents and increased their risk of suicide, yet didn't divulge the information as "it would be commercially unacceptable to include a statement that efficacy had not been demonstrated."
[REDDIT] https://www.reddit.com/r/science/comments/3l8r8l/restoring_study_329_efficacy_and_harms_of/
Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. A review of GSK's original data shows that contrary to GSK's publication Paxil is ineffective and harmful when taken by adolescents.
[REDDIT] https://www.reddit.com/r/paroxetine/ [archived]
This is a subreddit where people can discuss the ssri paroxetine/paxil. If you are interested in becoming a moderator for this subreddit, please contact me via PM.
[REDDIT] https://www.reddit.com/r/medicine/comments/13b4lx0/is_there_a_way_to_keep_the_phone_number_and/ [archived]
r/medicine is a virtual lounge for physicians and other medical professionals from around the world to talk about the latest advances, controversies, ask questions of each other, have a laugh, or share a difficult moment. This is a highly moderated subreddit. Please read the rule…
[REDDIT] https://www.reddit.com/r/PAstudent/comments/x33nq4/free_eor_study_guides/ [archived]
Here is a link to all my EOR study guides made based off of PAEA topic lists/blueprints: EOR guides
[REDDIT] https://www.reddit.com/r/medicine/comments/3ldjp7/skewed_research_pharma_and_paroxetine/
So BMJ released a scathing re-analysis yesterday of a study of paroxetine in depressed adolescents - tldr the original authors, aided by nonacademic ghostwriting, used non a priori outcomes and hid or worked the data to downplay inefficacy and adverse effects, while concluding th…

CROSS-REFERENCE

→ SHARES-EVENT Study 329: Paroxetine Clinical Trial Data Suppression and Publication Bias — This dossier directly investigates the context and consequences of Study 329, which is the subject of the linked document.
→ PARALLEL-PATTERN Tuskegee Syphilis Study: Government Medical Experimentation and 1972 Exposure — Both Study 329 and the Tuskegee Syphilis Study involve questions of ethical conduct in medical research and the well-being of vulnerable populations, despite differing contexts.
→ PARALLEL-PATTERN MKUltra University and Medical Institution Funding: Disclosure and Institutional Review — Both cases involve questions of ethical oversight and transparency in research, particularly when corporate or governmental interests might influence outcomes or disclosures.