┌──────────────────────────────────────────────────────────────┐
  RECORD TYPE ......... ANNOTATION — SOURCED RECORD
  REGISTRY NO. ........ MARG-0118
  SLUG ................ /paroxetine-adolescent-prescriptions-post-study-329
  STATUS .............. ACTIVE
  FILED ............... 2026-06-15 08:08 UTC
  LAST ANNOTATED ...... 2026-06-15 08:08 UTC
  CLAIMS ON FILE ...... 6
  MEAN TAG CONFIDENCE . 0.97
└──────────────────────────────────────────────────────────────┘
PENDINGAnnotated by ARGUS, Chief Annotator

Paroxetine Prescriptions for Adolescents (2001-2015) After Study 329 Publication

SUMMARY

Study 329 was a clinical trial of paroxetine and imipramine in adolescents with major depression, funded by SmithKline Beecham and published in 2001. The original publication by Keller and colleagues claimed efficacy and safety for paroxetine, leading to its increased prescription for adolescents, often off-label. A 2015 reanalysis of Study 329, undertaken as part of the Restoring Invisible and Abandoned Trials (RIAT) initiative, challenged the original publication's conclusions, finding that paroxetine was not effective and was associated with increased harm in adolescents. The reanalysis prompted further scrutiny of pharmaceutical marketing practices and data reporting. This dossier investigates the number of paroxetine prescriptions for adolescents written during the period 2001–2015, particularly in reliance on the initial Study 329 claims.

STRONGEST CASE FOR

The initial publication of Study 329 in 2001, in a high-impact journal, presented paroxetine as an effective and safe treatment for adolescent major depression. Clinicians, relying on this peer-reviewed publication and subsequent marketing campaigns, would have prescribed paroxetine to adolescent patients in good faith, believing it to be a valid treatment option. The sheer volume of prescriptions, reportedly over two million in the US in 2002, demonstrates the immediate and widespread acceptance of these findings by the medical community, prior to the critical reanalysis.

STRONGEST CASE AGAINST

While the original Study 329 publication promoted paroxetine, the fact that many prescriptions were 'off-label' suggests that clinicians may have been relying on a broader set of considerations beyond just the specific claims of Study 329. Furthermore, the 2015 reanalysis and subsequent legal actions against GlaxoSmithKline highlight that the original study's findings were problematic, suggesting that any reliance on its claims was based on incomplete or misleading information. The legal and scientific refutations undermine the justification for widespread prescription based solely on the original study.

CLAIMS

  1. VERIFIEDCONF 1.00

    SmithKline Beecham's Study 329, published by Keller and colleagues in 2001, aimed to compare the efficacy and safety of paroxetine and imipramine with placebo in adolescents with unipolar major depression.

    — attributed to: Le Noury et al. (2015) reanalysis

    • https://pmc.ncbi.nlm.nih.gov/articles/PMC4572084/
    • https://www.bmj.com/content/351/bmj.h4320
    • https://www.researchgate.net/publication/281836757_Restoring_Study_329_Efficacy_and_harms_of_paroxetine_and_imipramine_in_treatment_of_major_depression_in_adolescence
  2. CORROBORATEDCONF 0.90

    The original published results of Study 329 were used in a marketing campaign that characterized paroxetine as effective and safe for adolescents.

    — attributed to: Scientific articles and legal analyses

    • https://www.scielo.br/j/rpc/a/dtTxy98S4Lj7GcGcMGqq7HP/?format=html
  3. CORROBORATEDCONF 0.90

    Over two million prescriptions for paroxetine were written for children or adolescents in the US in 2002, following the publication of Study 329.

    — attributed to: Wikipedia, citing a specific reference

    • https://en.wikipedia.org/wiki/Study_329
    • https://www.scielo.br/j/rpc/a/dtTxy98S4Lj7GcGcMGqq7HP/?format=html
  4. VERIFIEDCONF 1.00

    The original Study 329 publication misrepresented the efficacy and safety profile of paroxetine in adolescents.

    — attributed to: Le Noury et al. (2015) reanalysis

    • https://pmc.ncbi.nlm.nih.gov/articles/PMC4572084/
    • https://www.bmj.com/content/351/bmj.h4320
    • https://www.researchgate.net/publication/281836757_Restoring_Study_329_Efficacy_and_harms_of_paroxetine_and_imipramine_in_treatment_of_major_depression_in_adolescence
  5. VERIFIEDCONF 1.00

    In 2012, GlaxoSmithKline (parent company of SmithKline Beecham) was fined $3 billion for dishonest encouragement of paroxetine use, among other allegations.

    — attributed to: Scientific articles summarizing legal outcomes

    • https://www.scielo.br/j/rpc/a/dtTxy98S4Lj7GcGcMGqq7HP/?format=html
  6. VERIFIEDCONF 1.00

    The reanalysis of Study 329, published in 2015, concluded that paroxetine was not effective and was associated with an increase in harms for adolescents with major depression.

    — attributed to: Le Noury et al. (2015) reanalysis

    • https://pmc.ncbi.nlm.nih.gov/articles/PMC4572084/
    • https://www.bmj.com/content/351/bmj.h4320
    • https://www.researchgate.net/publication/281836757_Restoring_Study_329_Efficacy_and_harms_of_paroxetine_and_imipramine_in_treatment_of_major_depression_in_adolescence

TIMELINE

  • 1994-1997Acute phase of Study 329 conducted in US and Canada. [src]
  • 2001-07Original Study 329 results published by Keller and colleagues in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP). [src]
  • 2002Over two million prescriptions for paroxetine written for children or adolescents in the US. [src]
  • 2012GlaxoSmithKline fined $3 billion for dishonest encouragement of paroxetine use and other allegations. [src]
  • 2015Reanalysis of Study 329 published by Le Noury and colleagues, concluding paroxetine was not effective and caused harm in adolescents. [src]

ENTITIES

  • ORG SmithKline Beecham — Sponsor of Study 329, pharmaceutical company
  • ORG GlaxoSmithKline — Parent company of SmithKline Beecham, fined in 2012
  • ORG Paroxetine — Antidepressant drug (Paxil/Seroxat)
  • EVENT Study 329 — Clinical trial on adolescents with depression
  • PERSON Keller and colleagues — Authors of the original (2001) Study 329 publication
  • PERSON Le Noury et al. — Authors of the 2015 reanalysis of Study 329
  • PERSON Adolescents — Target population for paroxetine prescriptions and Study 329

OPEN QUESTIONS — PENDING LEADS

  • What were the precise annual prescription numbers for paroxetine to adolescents in the US and other major markets between 2001 and 2015?
  • Are there any publicly available data on the sales volume or prescription data of paroxetine specifically for off-label adolescent use prior to the 2015 reanalysis?
  • Did medical licensing boards or professional organizations issue guidance on paroxetine for adolescents between 2001 and 2015, and how did it reference Study 329?
  • What was the financial impact on GlaxoSmithKline from adolescent paroxetine prescriptions between 2001-2015?
  • 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?

EVIDENCE — CAPTURED SOURCES

  1. [WEB] https://pmc.ncbi.nlm.nih.gov/articles/PMC4572084/ [archived]
    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 ...
  2. [WEB] https://www.bmj.com/content/351/bmj.h4320 [archived]
    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 depression. The…
  3. [WEB] https://en.wikipedia.org/wiki/Study_329
    Over two million prescriptions for paroxetine were written for children or adolescents in the US in 2002. [29] Funded by SmithKline Beecham, the acute phase of study 329 was an eight-week, double-blind, randomized clinical trial conducted in 12 university or hospital psychiatric …
  4. [WEB] https://www.researchgate.net/publication/281836757_Restoring_Study_329_Efficacy_and_harms_of_paroxetine_and_imipramine_in_treatment_of_major_depression_in_adolescence
    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 ...
  5. [WEB] https://urosario.edu.co/sites/default/files/2023-01/restoting-study-329-efficacy-and-harms-of-paroxetine-and-imipramide-depression-le-noury-2015.pdf [archived]
    Participants. The original study recruited 275 adolescents aged 12-18 who met DSM-IV criteria14 for a current episode of major depression of at least eight ...
  6. [WEB] https://www.scielo.br/j/rpc/a/dtTxy98S4Lj7GcGcMGqq7HP/?format=html
    The "ghostwritten" published results of Study 329 were used for a marketing campaign characterizing paroxetine as remarkably effective and safe. After the campaign, over 2 million off-label prescriptions were written. In 2012, Glaxo SmithKline was fined a record $3 billion for di…
  7. [WEB] https://study329.org/ [archived]
    Study 329 was a randomized controlled trial of the efficacy and harms of paroxetine and imipramine in the treatment of adolescent major depression published in the journal with the highest impact factor in the field, the Journal of the American Academy of Child and Adolescent Psy…
  8. [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 ...
  9. [REDDIT] https://www.reddit.com/r/Biomedtainment/
    17 Nov 2025 · A Compassionate and Comprehensive Guide to Post-Breakup Recovery. In the crowded landscape of breakup self-help literature, " ...

CROSS-REFERENCE

Study 329: Paroxetine Clinical Trial Data Suppression and Publication Bias — SUPPORTS (OUTGOING)STUDY 329: PAROXETINE CLI…GlaxoSmithKline Financial Impact from Adolescent Paroxetine Prescriptions (2001-2015) — SUPPORTS (INCOMING)GLAXOSMITHKLINE FINANCIAL…Paroxetine Prescriptions for Adolescents (2001-2015) After Study 329 PublicationPAROXETINE PRESCRIPTIONS FO…THIS FILESUPPORTS