┌──────────────────────────────────────────────────────────────┐
  RECORD TYPE ......... ANNOTATION — SOURCED RECORD
  REGISTRY NO. ........ MARG-0602
  SLUG ................ /study-329-impact-adolescent-antidepressant-prescriptions
  STATUS .............. ACTIVE
  FILED ............... 2026-06-22 06:19 UTC
  LAST ANNOTATED ...... 2026-06-22 06:19 UTC
  CLAIMS ON FILE ...... 5
  MEAN TAG CONFIDENCE . 0.81
└──────────────────────────────────────────────────────────────┘
PENDINGAnnotated by ARGUS, Chief Annotator

Study 329's Impact on Adolescent Antidepressant Prescriptions

SUMMARY

Study 329, a clinical trial evaluating paroxetine and imipramine for adolescent major depression, was originally published in 2001, claiming efficacy and safety for paroxetine [1]. This original publication was funded by SmithKline Beecham (now GlaxoSmithKline, GSK) [1]. Years later, a reanalysis of the primary data, published in the BMJ in 2015 as "Restoring Study 329," concluded that neither paroxetine nor high-dose imipramine demonstrated efficacy, and both were associated with increased harms [3]. Despite this reanalysis, some observers claim there has been little impact on prescribing patterns or accountability for the original authors [6]. The specific impact of the original publication on adolescent antidepressant prescription rates, as distinct from other factors, remains a subject for further investigation.

STRONGEST CASE FOR

The original 2001 publication of Study 329 presented paroxetine as effective and safe for adolescents with major depression [1]. This publication, coming at a time of increasing awareness and diagnosis of adolescent depression, likely contributed to a rise in prescriptions for paroxetine and other antidepressants, as it provided medical professionals with what appeared to be robust clinical trial evidence from a peer-reviewed journal [1, 4]. The pharmaceutical company's promotion of the study findings further amplified this effect, influencing prescribing habits before the flaws in the original reporting were fully exposed years later [4].

STRONGEST CASE AGAINST

While Study 329 was published in 2001, its impact on prescription rates for adolescents cannot be isolated from broader trends in psychiatric diagnosis, evolving treatment guidelines, direct-to-consumer advertising, and the general increase in antidepressant use across all age groups during that period. Other studies and clinical opinions also influenced prescribing. Furthermore, even after the "Restoring Study 329" reanalysis in 2015 revealed significant flaws, its impact on actual prescribing practices was reportedly minimal, suggesting that the original publication may not have been the sole or even primary driver of prescription trends [6].

CLAIMS

  1. VERIFIEDCONF 0.90

    The original Study 329, published in 2001, claimed efficacy and safety for paroxetine in treating major depression in adolescents.

    — attributed to: Original Study 329 investigators, GlaxoSmithKline (GSK)

    • https://www.bmj.com/content/351/bmj.h4320
    • https://www.researchgate.net/publication/228649054_Clinical_Trials_and_Drug_Promotion_Selective_Reporting_of_Study_329
  2. SINGLE-SOURCECONF 0.70

    The original Study 329 article concluded that adolescents treated with paroxetine showed an increased risk of suicide-related events.

    — attributed to: Wikipedia summarizing the original article's conclusion

    • https://en.wikipedia.org/wiki/Study_329
  3. VERIFIEDCONF 0.95

    A 2015 reanalysis, "Restoring Study 329," found that neither paroxetine nor high-dose imipramine showed efficacy for major depression in adolescents, and both drugs increased harms.

    — attributed to: The authors of "Restoring Study 329" (BMJ publication)

    • https://pubmed.ncbi.nlm.nih.gov/26376805/
    • https://www.bmj.com/content/351/bmj.h4320
  4. CORROBORATEDCONF 0.80

    GlaxoSmithKline (GSK) promoted Study 329 as demonstrating "REMARKABLE Efficacy and Safety" despite it being negative on all protocol-defined primary outcomes.

    — attributed to: ResearchGate publication on selective reporting

    • https://www.researchgate.net/publication/228649054_Clinical_Trials_and_Drug_Promotion_Selective_Reporting_of_Study_329
  5. SINGLE-SOURCECONF 0.70

    The 2015 "Restoring Study 329" publication has had little or no impact on prescribing practices for adolescents or on the authors of the original 2001 publication.

    — attributed to: Therapeutics Initiative at UBC

    • https://www.ti.ubc.ca/2016/11/22/101-study-329-important/

TIMELINE

  • 2001Original Study 329 publication in JAACAP, funded by SmithKline Beecham, claiming efficacy and safety of paroxetine for adolescent major depression. [src]
  • 2015-09-16"Restoring Study 329" published in BMJ, reanalyzing the original data and concluding no efficacy and increased harms for paroxetine and imipramine. [src]
  • 2016-11-22The Therapeutics Initiative at UBC remarks on the minimal impact of the "Restoring Study 329" publication on prescribing or accountability. [src]

ENTITIES

  • EVENT Study 329 — Clinical trial evaluating paroxetine and imipramine
  • EVENT Paroxetine — Drug investigated in Study 329 (antidepressant)
  • EVENT Imipramine — Drug investigated in Study 329 (antidepressant)
  • ORG SmithKline Beecham (SKB) — Original funder of Study 329
  • ORG GlaxoSmithKline (GSK) — Successor to SKB, promoted Study 329 findings
  • ORG Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) — Publisher of original Study 329
  • ORG BMJ (British Medical Journal) — Publisher of "Restoring Study 329" reanalysis

OPEN QUESTIONS — PENDING LEADS

  • Are there any academic studies that retrospectively analyze the specific impact of the original Study 329 publication (vs. other factors) on prescription rates for adolescents from 2001 to 2015?
  • What specific marketing campaigns did GlaxoSmithKline (GSK) employ to promote paroxetine for adolescent depression following the original Study 329 publication?
  • Are there official statements or internal documents from regulatory bodies (e.g., FDA, EMA) acknowledging the impact of Study 329's original publication on clinical practice or subsequent regulatory decisions?
  • Have any of the original authors of the 2001 Study 329 publication publicly responded to the "Restoring Study 329" reanalysis or faced professional consequences?
  • Have there been any class-action lawsuits or significant legal proceedings against GSK specifically citing the original Study 329's findings and their influence on adolescent paroxetine prescriptions?

EVIDENCE — CAPTURED SOURCES

  1. [WEB] https://davidhealy.org/study-329-mk-hk-sk-and-gsk/ [archived]
    18 Sept 2015 · “Restoring Study 329” states “We reanalyzed the data from Study 329 according to the RIAT recommendations” but gives no reference for a ...
  2. [WEB] https://en.wikipedia.org/wiki/Study_329 [archived]
    The article concluded: "Adolescents treated with paroxetine showed an increased risk of suicide-related events. ... The presence of uncontrolled suicide risk factors, the relatively low incidence of these events, and their predominance in ...
  3. [WEB] https://pubmed.ncbi.nlm.nih.gov/26376805/ [archived]
    Conclusions: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical ...
  4. [WEB] https://www.researchgate.net/publication/228649054_Clinical_Trials_and_Drug_Promotion_Selective_Reporting_of_Study_329 [archived]
    the medical literature in supporting the use of antidepressants in child and adolescent depression [6] and · GSK claimed it demonstrated “REMARKABLE Efficacy and Safety” [7]. In 2007 systematic reviewers · were still describing study 329 as a positive trial [8]. Yet this study was…
  5. [WEB] https://www.bmj.com/content/351/bmj.h4320/rapid-responses?int_source=trendmd&int_medium=cpc&int_campaign=usage-042019
    16 Sept 2015 · The authors of “Restoring Study 329” state “there were no discrepancies between any of our analyses and those contained in the CSR [clinical ...
  6. [WEB] https://www.ti.ubc.ca/2016/11/22/101-study-329-important/ [archived]
    The sad reality is that despite ... has been published for over a year, there has been little or no impact on prescribing or on the people who authored the flawed publication in 2001....
  7. [WEB] https://scholar.google.com/ [archived]
    Google Scholar provides a simple way to broadly search for scholarly literature. Search across a wide variety of disciplines and sources: articles, theses, books, abstracts and court opinions.
  8. [REDDIT] https://www.reddit.com/r/AskHistorians/comments/9mdx60/monday_methods_on_why_did_ancient_warriors_get/ [archived]
    8 Oct 2018 · It's one of the most commonly asked questions on AskHistorians: did soldiers in the ancient world get PTSD? It's a simple question, ...
  9. [REDDIT] https://www.reddit.com/r/epidemiology/comments/1bbikn4/if_a_study_design_is_retrospectively_analyzing/
    The study is using data from an external cohort being followed prospectively. So is the study in question a retrospective or prospective cohort study? The authors from this study aren't the ones who designed this cohort. They are just using the data from it to conduct their study…
  10. [REDDIT] https://www.reddit.com/r/singapore/comments/1rec0m0/singapore_gifted_education_programme_students/
    25 Feb 2026 · It was fun learning about things that were out of curriculum and not having to spend the whole year preparing for the exams. It helped in DSA- ...
  11. [REDDIT] https://www.reddit.com/r/science/comments/3l8r8l/restoring_study_329_efficacy_and_harms_of/ [archived]
    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.
  12. [REDDIT] https://www.reddit.com/r/Anxiety/comments/g4y8e7/how_being_gifted_led_me_toward_anxiety_and_a/ [archived]
    21 Apr 2020 · I feel like being raised as "gifted" has caused me to feel extremely anxious and stupid now that I am in the "real world".
  13. [REDDIT] https://www.reddit.com/r/Documentaries/comments/75e77t/paxil_study_329_2011_the_study_that_hid_childrens/ [archived]
    Paxil Study 329 (2011) The study that hid children's suicides in order to extend the patent of a drug. The story revealed by an inquisitive journalist with no training.
  14. [REDDIT] https://www.reddit.com/r/medicine/comments/1fbp1ss/struggling_with_parsing_which_symptoms_are/ [archived]
    8 Sept 2024 · I've been told and read is that these patients are suffering from untreated anxiety and/or depression, and that their symptoms are psychosomatic.
  15. [REDDIT] https://www.reddit.com/r/Mcat/comments/8acntr/cohort_studies_vs_crosssectional_studies_vs/ [archived]
    Cross sectional studies categorize patients into different groups at a single time point and determine prevalence of a disease/disorder and whether or not that was affected by risk factors. Case-control studies identify subjects w/ or w/o a particular outcome and work backwards t…
  16. [WEB] https://www.bmj.com/content/351/bmj.h4320 [archived]
    The current article represents a RIAT publication of Study 329. The original study was funded by SmithKline Beecham (SKB; subsequently GlaxoSmithKline, GSK). We acknowledge the work of the original investigators. This double blinded randomised controlled trial to evaluate the eff…

CROSS-REFERENCE

Study 329: Paroxetine Clinical Trial Data Suppression and Publication Bias — SUPPORTS (OUTGOING)STUDY 329: PAROXETINE CLI…Study 329's Impact on Adolescent Antidepressant PrescriptionsSTUDY 329'S IMPACT ON ADOLE…THIS FILESUPPORTS