Restoring TADS: RIAT reanalysis of the Treatment for Adolescents with Depression Study
Bibliographic record
Abstract
Background The Treatment for Adolescents with Depression Study (TADS) continues to influence international clinical practice guidelines for adolescent depression. Objective We assessed TADS’ effectiveness and harms through a Restoring Invisible and Abandoned Trials (RIAT)-led reanalysis. Methods TADS was a phase-three multicentre, parallel four-arm randomised controlled superiority trial that randomised adolescents ( n = 439) to fluoxetine alone (FLX), CBT alone (CBT), open-label fluoxetine plus CBT (COMB) or placebo pill alone (PBO) over 12 weeks. COMB and CBT groups were unblinded to their treatment allocation. Primary outcomes were the Children’s Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impression-Improvement scale (CGI-I). Results Our ITT reanalysis showed a significant decrease in CDRS-R at 12 weeks in COMB compared with PBO (−6.65; p < 0.001) and CBT (−7.63, p < 0.001), but not FLX (−4.07, p = 0.063). There was no difference between FLX, CBT and PBO. There was a higher proportion of CGI-I responders in COMB (73.72% [SE 4.43]) compared with all other arms: FLX (64.16% [SE 4.76]), CBT (51.06% [SE 5.29]) and PBO (38.76% [SE 4.87]; all p < 0.001); FLX had more responders than PBO ( p = 0.004). 369 adverse events were reported for 171 participants, with 66% occurring in those taking fluoxetine. We found 32 serious adverse events (22 in those taking fluoxetine), which varied from original authors’ reporting. Conclusions Our reanalysis replicated the original investigators’ reporting that COMB demonstrated the most robust outcomes and that FLX was not superior to PBO. In contrast to the original TADS Team’s reporting, there was a higher level of harm uncovered in allocation groups taking fluoxetine, including 11 unreported suicide-related adverse events. Overall, the marked increase in harms among participants taking fluoxetine warrants further circumspection when prescribing it to adolescents.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".