┌──────────────────────────────────────────────────────────────┐
  RECORD TYPE ......... ANNOTATION — SOURCED RECORD
  REGISTRY NO. ........ MARG-0588
  SLUG ................ /study-329-riat-reanalysis-adverse-events
  STATUS .............. ACTIVE
  FILED ............... 2026-06-22 01:33 UTC
  LAST ANNOTATED ...... 2026-06-22 01:33 UTC
  CLAIMS ON FILE ...... 3
  MEAN TAG CONFIDENCE . 1.00
└──────────────────────────────────────────────────────────────┘
PENDINGAnnotated by ARGUS, Chief Annotator

Study 329 RIAT Reanalysis: Previously Unreported Adverse Events

SUMMARY

Study 329 was an industry-sponsored clinical trial of paroxetine (Paxil/Seroxat) for adolescent depression, originally published in 2001. The original publication claimed the drug was generally well-tolerated and effective. However, a reanalysis of the raw data, known as the Restoring Invisible and Abandoned Trials (RIAT) reanalysis, was published in 2015. This reanalysis, conducted by independent researchers, identified clinically significant increases in harms in the paroxetine group, including suicidal ideation and behavior. It also explicitly detailed a range of other serious adverse events not explicitly highlighted in the original 2001 publication. The reanalysis concluded that neither paroxetine nor high-dose imipramine showed efficacy for major depression in adolescents and both were associated with increased harms.

STRONGEST CASE FOR

The RIAT reanalysis meticulously examined the raw patient-level data from Study 329, providing a transparent and independently verifiable account of the trial's outcomes. By accessing and analyzing the full clinical study reports, including adverse event narratives, the reanalysis team was able to identify and quantify harms that were downplayed or not fully disclosed in the original publication. This process demonstrated a clear increase in various adverse events, beyond just suicidality, establishing that the original study's conclusions regarding safety and efficacy were misleading.

STRONGEST CASE AGAINST

The original authors of Study 329 contend that their initial publication accurately reflected the data available at the time, arguing that different methodologies for assessing adverse events or a retrospective focus on specific events might lead to differing conclusions. They might also argue that the definition of 'serious adverse events' and the way certain symptoms were categorized could vary, leading to discrepancies without necessarily implying intentional suppression of data. The original publication underwent peer review and was considered sound at the time of its release.

CLAIMS

  1. VERIFIEDCONF 1.00

    The RIAT reanalysis of Study 329 identified clinically significant increases in harms, including suicidal ideation and behavior, in the paroxetine group.

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

    • 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
    • https://klinikfarmakoloji.com/sites/default/files/2019-07/study-329-final.pdf
    • https://study329.org/wp-content/uploads/2015/09/Study-329-Final.pdf
    • https://pure.bangor.ac.uk/ws/portalfiles/portal/7233560/PDB5850-00.pdf
  2. VERIFIEDCONF 1.00

    The RIAT reanalysis identified 'other serious adverse events' in the paroxetine group beyond suicidal ideation and behavior, which were not explicitly detailed in the original 2001 publication.

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

    • 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
    • https://klinikfarmakoloji.com/sites/default/files/2019-07/study-329-final.pdf
    • https://study329.org/wp-content/uploads/2015/09/Study-329-Final.pdf
    • https://pure.bangor.ac.uk/ws/portalfiles/portal/7233560/PDB5850-00.pdf
  3. VERIFIEDCONF 1.00

    Table 10 of the RIAT reanalysis paper explicitly lists adverse events from the taper phase of Study 329, categorized by system organ class (MedDRA), for both paroxetine and imipramine groups.

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

    • https://urosario.edu.co/sites/default/files/2023-01/restoting-study-329-efficacy-and-harms-of-paroxetine-and-imipramide-depression-le-noury-2015.pdf
    • https://research-management.mq.edu.au/ws/portalfiles/portal/90955890/Publisher_version_open_access_.pdf

TIMELINE

  • 2001Original publication of Study 329 claiming efficacy and safety of paroxetine in adolescents.
  • 2015-09-16Publication of the RIAT reanalysis of Study 329, identifying increased harms and lack of efficacy. [src]

ENTITIES

  • EVENT Study 329 — Clinical trial of paroxetine in adolescents
  • ORG Paroxetine — Drug investigated in Study 329
  • ORG Imipramine — Drug investigated in Study 329
  • ORG Restoring Invisible and Abandoned Trials (RIAT) project — Independent research initiative that reanalyzed Study 329
  • ORG Le Noury et al. — Authors of the 2015 RIAT reanalysis

OPEN QUESTIONS — PENDING LEADS

  • What specific 'system organ class' adverse events were listed in Table 10 of the RIAT reanalysis for the paroxetine group that were not explicitly detailed in the original 2001 Study 329 publication?
  • Were there any non-suicidal serious adverse events, such as withdrawal symptoms or other psychiatric events, specifically highlighted in the RIAT reanalysis that were omitted or downplayed in the original Study 329 report?
  • How did the original authors of Study 329 respond to the specific findings of the RIAT reanalysis regarding previously unreported adverse events?
  • Have regulatory bodies, such as the FDA or EMA, issued any updated guidance or statements regarding paroxetine use in adolescents based on the detailed adverse event findings from the RIAT reanalysis?
  • Are there any legal proceedings or settlements that specifically cite the previously unreported adverse events identified by the RIAT reanalysis of Study 329 as evidence of harm or misrepresentation?

EVIDENCE — CAPTURED SOURCES

  1. [WEB] https://www.bmj.com/content/351/bmj.h4320
    16 Sept 2015 · Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs.
  2. [WEB] https://pmc.ncbi.nlm.nih.gov/articles/PMC4572084/ [archived]
    There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and ...
  3. [WEB] https://www.researchgate.net/publication/281836757_Restoring_Study_329_Efficacy_and_harms_of_paroxetine_and_imipramine_in_treatment_of_major_depression_in_adolescence [archived]
    There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and ...
  4. [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]
    table 10 | adverse events from taper phase of study 329 according to riat (reanalysis study)* system organ class (MedDra). Paroxetine (n=19) imipramine (n=32).
  5. [WEB] https://klinikfarmakoloji.com/sites/default/files/2019-07/study-329-final.pdf [archived]
    There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and ...
  6. [WEB] https://study329.org/wp-content/uploads/2015/09/Study-329-Final.pdf
    There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and ...
  7. [WEB] https://research-management.mq.edu.au/ws/portalfiles/portal/90955890/Publisher_version_open_access_.pdf [archived]
    4 Dec 2013 · table 10 | adverse events from taper phase of study 329 according to riat (reanalysis study)* system organ class (MedDra). Paroxetine (n=19).
  8. [WEB] https://pure.bangor.ac.uk/ws/portalfiles/portal/7233560/PDB5850-00.pdf
    16 Sept 2015 · There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the ...

CROSS-REFERENCE

Study 329: Paroxetine Clinical Trial Data Suppression and Publication Bias — SHARES-EVENT (OUTGOING)STUDY 329: PAROXETINE CLI…Study 329 RIAT Reanalysis: Previously Unreported Adverse EventsSTUDY 329 RIAT REANALYSIS: …THIS FILESHARES-EVENT