Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.088
- Threshold uncertainty score
- 0.343
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.228 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Importance: To our knowledge, no study has previously evaluated whether individuals with bipolar depression enriched a priori on the basis of biochemical and/or phenotypic immuno-inflammatory activation would differentially respond to an anti-inflammatory agent for the treatment of depressive symptoms. Objective: To assess the antidepressant efficacy of adjunctive infliximab, a monoclonal antibody targeting tumor necrosis factor, in adults with bipolar I and bipolar II depression and inflammatory conditions. Design, Setting, and Participants: This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at 2 outpatient tertiary care sites in Canada and the United States. Eligible adults (aged 18-65 years) met DSM-5-defined criteria for bipolar I or bipolar II depression and exhibited pretreatment biochemical and/or phenotypic evidence of inflammatory activation. Participants were enrolled between October 1, 2015, and April 30, 2018. Data analysis was performed from May 1 through July 31, 2018, using modified intent-to-treat analysis. Interventions: Patients were randomized to receive 3 intravenous infusions of infliximab therapy or placebo at baseline and at weeks 2 and 6 of the 12-week study. Main Outcomes and Measures: The primary efficacy outcome was baseline-to-end point (ie, week-12) change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. History of childhood maltreatment, as assessed by the Childhood Trauma Questionnaire, was used for exploratory analyses as 1 of several secondary outcomes. Results: A total of 60 participants were randomized to infliximab (n = 29 [48%]; mean [SD] age, 45.0 [11.7] years; 20 of 28 female [71%]) or to placebo (n = 31 [52%]; mean [SD] age, 46.8 [10.2] years; 26 of 30 female [87%]) across study sites. Overall baseline-to-end point change in MADRS total score was observed across treatment × time interaction (χ2 = 10.33; P = .04); reduction in symptom severity was not significant at week 12 (relative risk, 1.09; 95% CI, 0.80-1.50; df = 1; P = .60). As part of a secondary analysis, a significant treatment × time × childhood maltreatment interaction was observed in which infliximab-treated individuals with childhood history of physical abuse exhibited greater reductions in MADRS total score (χ2 = 12.20; P = .02) and higher response rates (≥50% reduction in MADRS total score) (χ2 = 4.05; P = .04). Conclusions and Relevance: Infliximab did not significantly reduce depressive symptoms compared with placebo in adults with bipolar depression. Results from secondary analyses identified a subpopulation (ie, those reporting physical and/or sexual abuse) that exhibited a significant reduction in depressive symptoms with infliximab treatment compared with placebo. Trial Registration: ClinicalTrials.gov identifier: NCT02363738.
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.
The record
- Venue
- JAMA Psychiatry
- Topic
- Tryptophan and brain disorders
- Field
- Neuroscience
- Canadian institutions
- University of OttawaUniversity Health NetworkUniversity of Toronto
- Funders
- Daiichi Sankyo EuropeNational Institute on Drug AbusePfizerNational Institute of Mental HealthNational Institutes of HealthAllerganSunovionCanadian Institutes of Health ResearchCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorPalo Alto Health SciencesH. Lundbeck A/SStanley Medical Research InstitutePurdue University
- Keywords
- InfliximabMedicineRandomized controlled trialBipolar disorderInternal medicineDepression (economics)PlaceboAdjunctive treatmentBipolar II disorderMontgomery–Åsberg Depression Rating ScaleMajor depressive episodePsychiatryPlacebo-controlled studyPediatricsPhysical therapyMoodMajor depressive disorderDouble blindTumor necrosis factor alpha
- Has abstract in OpenAlex
- yes