Effect of Cariprazine on Anhedonia in Patients with Bipolar I Depression: Post Hoc Analysis of Three Randomized Placebo-Controlled Clinical Trials
Bibliographic record
Abstract
Anhedonic symptoms in bipolar I (BP-I) depression are associated with decreased quality of life and impaired functioning. We evaluated the effects of cariprazine in patients with BP-I depression with lower or higher levels of anhedonia at baseline. Data were pooled from three clinical trials (NCT01396447, NCT02670538, NCT02670551) analyzing the effects of cariprazine 1.5 and 3 mg/day in adults with BP-I depression. During post hoc analysis, patients were stratified by baseline median Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor score into a lower (score < median) or higher (score ≥ median) anhedonia subgroup. Outcomes included change from baseline to week 6 in MADRS total and anhedonia factor score, with the latter also evaluated after adjusting for other depressive symptoms. Between-group differences in change from baseline to week 6 were compared using least-squares mean differences (LSMD) analyzed via a mixed-effect model for repeated measures. Median baseline anhedonia factor score was 19, defining the lower (placebo = 211; cariprazine 1.5 mg/day = 200, 3 mg/day = 212) and higher (placebo = 249; cariprazine 1.5 mg/day = 261, 3 mg/day = 250) anhedonia subgroups. In the lower subgroup, cariprazine 1.5 mg/day but not 3 mg/day was superior to placebo in reducing MADRS total (LSMD [95% CI] 1.5 mg/day = − 2.61 [− 4.28, − 0.93], P = .0024) and anhedonia factor scores (− 1.70 [− 2.77, − 0.62], P = .0021) at week 6. In the higher subgroup, both cariprazine doses were associated with significantly greater reductions than placebo in MADRS total (1.5 mg/day = − 3.01 [− 4.84, − 1.19], P = .0012; 3 mg/day = − 3.26 [− 5.12, − 1.40], P = .0006) and anhedonia factor scores (1.5 mg/day = − 1.97 [− 3.13, − 0.81], P = .0009; 3 mg/day = − 2.07 [− 3.26, − 0.89], P = .0006). Anti-anhedonic effects were preserved after adjusting for other depressive symptoms, suggesting the effect was not pseudospecific. Patients in the higher subgroup had higher baseline depression and therefore the lower subgroup may have had a floor effect. Cariprazine demonstrated antidepressant and specific anti-anhedonic effects regardless of baseline anhedonia symptoms in patients with BP-I depression. ClinicalTrials.gov identifiers, NCT02670538, NCT02670551, NCT01396447. Anhedonia, or the lack of interest or pleasure, is common in patients with bipolar I depression. Cariprazine is a medication approved for the treatment of bipolar I depression. However, its effect on anhedonia is unclear. To understand the effect of cariprazine on anhedonia, we combined data from three bipolar I depression trials. We compared the effect of cariprazine treatment (1.5 mg or 3 mg per day) for 6 weeks against placebo in patients who had lower and higher levels of anhedonia before they started treatment. A total of 1383 patients were included in the study. There were 623 patients with lower anhedonia and 760 with higher anhedonia. Patients with higher anhedonia were more depressed overall than those with lower anhedonia. In patients with lower anhedonia, cariprazine 1.5 mg per day was better than placebo at reducing both anhedonia and depression. In patients with higher anhedonia, both cariprazine doses were better than placebo at reducing anhedonia and depression. Our results suggest that cariprazine reduces symptoms of both depression and anhedonia in patients with bipolar I depression.
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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 | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 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".