Impact of Cariprazine on Anhedonia Symptoms in Patients with Bipolar I Depression: Pooled Analysis of 3 Pivotal Clinical Trials
Bibliographic record
Abstract
Purpose Anhedonia characterizes major depressive episodes in bipolar depression and is associated with more severe illness/poor prognosis. These post hoc analyses assess effect of cariprazine 1.5 and 3 mg/d on anhedonia symptoms in patients with bipolar I depression. Methods Data were pooled from 3 randomized, double-blind, placebo-controlled bipolar I depression trials in cariprazine. Cariprazine 1.5 and 3 mg/d versus placebo were evaluated in patient subgroups stratified by median baseline MADRS anhedonia score (higher anhedonia=score ≥19; lower anhedonia=score <19). Outcomes included mean change from baseline to week 6 in MADRS total and anhedonia factor score (sum of apparent sadness, reported sadness, concentration, lassitude, and inability to feel items). The proportion of patients with week 6 anhedonia factor response (≥50% improvement from baseline) was also determined. Changes from baseline were analyzed using a mixed-effect model for repeated measures. Results There were 760 patients in the higher anhedonia subgroup (placebo=249, cariprazine: 1.5 mg/d=261; 3 mg/d=250) and 623 patients in the lower anhedonia subgroup (placebo=211, cariprazine: 1.5 mg/d=200; 3 mg/d=212). Mean baseline MADRS total score was higher in the higher anhedonia subgroup (total=33.6) than in the lower anhedonia subgroup (total=27.6). Change from baseline to week 6 in MADRS total score was greater for both cariprazine doses versus placebo in the higher anhedonia subgroup (least squares mean difference [LSMD] and 95% confidence interval [CI]: 1.5 mg/d=-3.01 [-4.84, -1.19], P =.0012; 3 mg/d: -3.26 [-5.12, -1.40], P =.0006); in the lower anhedonia subgroup, cariprazine 1.5 mg/d was statistically significant versus placebo (-2.61 [-4.28, -0.93], P =.0024). In the higher anhedonia subgroup at week 6, change from baseline in anhedonia factor score was significant versus placebo for both cariprazine doses (1.5 mg/d=-1.97 [-3.13, -0.81], P =.0009; 3 mg/d=-2.07 [-3.26, -0.89], P =.0006); in the lower subgroup, the difference was significant versus placebo for cariprazine 1.5 mg/d (-1.70 [-2.77, -0.62], P =.0021). After adjusting for changes in other depressive symptoms, LSMDs versus placebo in the anhedonia factor score remained significant for cariprazine 1.5 mg/d (-1.21 [-2.05, -0.36], P =.0052) and 3 mg/d (-1.00 [-1.86, -0.14], P =.0233) in the higher anhedonia subgroup, and for 1.5 mg/d (-1.06 [-1.92, -0.19], P =.0164) in the lower subgroup. In the higher anhedonia subgroup, rates of anhedonia factor response were greater versus placebo (31.7%) for cariprazine 1.5 mg/d (44.8%, P =.0028) and 3 mg/d (45.6%, P =.0019); in the lower subgroup, response rates were 39.3% for placebo, 48.0% for 1.5 mg/d, and 46.7% for 3 mg/d. Adverse events in ≥5% cariprazine and twice placebo were nausea, akathisia, restlessness, and EPS. Importance Those with bipolar depression and anhedonia cariprazine demonstrated a potent antidepressant and antianhedonic effect in higher/lower anhedonia subgroups. Funding AbbVie This data was previously presented at the European College of Neuropsychopharmacology (ECNP) Congress; Barcelona, Spain; October 7 – 10, 2023.
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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 | 0.001 |
| 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".