Exposure–Response Analysis for Aripiprazole Once‐Monthly in Patients Diagnosed With Bipolar I Disorder
Bibliographic record
Abstract
Aripiprazole once-monthly (AOM) is approved for the maintenance monotherapy treatment of bipolar I disorder (BP-I) in adults. A previously developed population pharmacokinetic model was validated by applying it to data from patients diagnosed with BP-I. The model was then used to generate aripiprazole exposures for an exposure-response model intended to describe the relationship between aripiprazole exposure and time to recurrence of any mood episode in patients with BP-I. The BP-I data were best described by a continuous model in which higher aripiprazole exposure was associated with a lower risk of recurrence. For each 1 ng/mL increase in aripiprazole plasma concentration, the predicted hazard for recurrence decreased by 0.34%. An aripiprazole plasma concentration of 95 ng/mL (clinically relevant in schizophrenia) was tested in a separate categorical model and was a significant predictor of time to recurrence (P = .0270), with a 36% (1.55-fold) decrease in the predicted risk of recurrence with an aripiprazole concentration of ≥95 versus <95 ng/mL. Plasma aripiprazole concentration was identified as an important predictor of recurrence in patients diagnosed with BP-I treated with AOM, highlighting the importance of maintenance therapy. A 95 ng/mL threshold is relevant in BP-I, but with a smaller effect size compared with that in schizophrenia.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".