Cariprazine as a transdiagnostic treatment for symptoms of depression across different disorders
Z. B. Dombi, R. Csehi, Á. BarabássyIntroduction
Symptoms of depression are prevalent across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia, yet treatment strategies are traditionally indication specific. Cariprazine, a dopamine D3/D2 partial agonist approved for all three disorders in the U.S., provides an opportunity to evaluate the efficacy of a single compound on depressive symptoms across diagnostic categories.
Objectives
This meta-analysis aimed to pool clinical trial data to determine the efficacy of cariprazine versus placebo in alleviating depressive symptoms, regardless of primary diagnosis.
Methods
Only randomized controlled trials comparing cariprazine with placebo were included. Data were drawn from post-hoc and pooled analyses across different psychiatric indications and dose ranges. The primary outcome was change from baseline in depressive symptom scores, standardized across trials by converting effect sizes to Cohen’s d.
Meta-analyses were performed in RStudio (version 2024.04.2+764) using the metafor package. A multilevel random-effects model accounted for overlapping placebo groups in trials with multiple dose arms, with comparisons grouped by study (random = ~1 | STUDY). Effect sizes are reported as pooled standardized mean differences (Cohen’s d) with 95% confidence intervals. Between-study heterogeneity was assessed using Q, I², and τ². Forest plots display individual and pooled estimates of cariprazine’s antidepressant effects.
Results
Four trials in bipolar depression (MD-52, MD-53, MD-54, MD-56; doses 1.5–3 mg/day) were included, alongside five adjunctive MDD trials (MD-71, MD-72, MD-75, 301, 302; doses 1–4.5 mg/day) and three schizophrenia studies (MD-04, MD-05, MD-16; pooled dose range 1.5–9 mg/day). Across all indications, the pooled least square mean difference in depressive symptoms for cariprazine versus placebo was –1.45 (95% CI: –2.18 to –0.71), indicating a significant overall benefit. The largest effects were observed in bipolar depression and MDD, with smaller but positive effects in schizophrenia, where depressive symptoms were assessed via the PANSS Depression/Anxiety Marder factor score rather than dedicated depression scales.
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