Global improvement with cariprazine in the treatment of bipolar I disorder and schizophrenia: A pooled post hoc analysis

Abstract

SummaryIntroductionGlobal rating scale measures are useful for assessing the clinical relevance of patient change. Cariprazine, a dopamine D3 and D2 receptor partial agonist, is FDA‐approved for the adult treatment of acute manic/mixed episodes of bipolar I disorder and schizophrenia. Post hoc evaluations of Clinical Global Impressions‐Severity (CGI‐S) scores from the cariprazine pivotal trials in both indications were conducted.MethodsData from 3 bipolar mania and 3 schizophrenia trials were pooled by indication (bipolar disorder = 1033; schizophrenia = 1466). Cariprazine‐ and placebo‐treated patients were categorised by baseline CGI‐S scores; the proportion of patients who improved from more severe categories at baseline to less severe categories at end‐point was evaluated using a logistic regression model. Correlations between Young Mania Rating Scale and Positive and Negative Syndrome Scale total score changes and category shifts were also evaluated.ResultsIn both disease states, more cariprazine‐ than placebo‐treated patients had improved CGI‐S scores at end‐point; more placebo‐treated patients had worse end‐point scores. More cariprazine‐ vs placebo‐treated patients shifted from the extremely/severely ill to mildly ill/better category (bipolar disorder = 55% vs 36%, odds ratio [OR] = 2.1; P = .09; schizophrenia = 42% vs 18%, OR = 3.4, P<.01). ORs was statistically significant in favour of cariprazine in shifts from marked and moderate illness to borderline/normal in both indications (P < .05). Correlations between rating scale improvement and category shift were greatest in patients with extreme/severe baseline illness for bipolar disorder (−0.853) and schizophrenia (−0.677).ConclusionsPost hoc analyses showed that more cariprazine‐ than placebo‐treated patients with bipolar mania or schizophrenia had statistically significant and clinically meaningful CGI‐S improvement.

Cariprazine for acute and maintenance treatment of adults with schizophrenia: an evidence-based review and place in therapy

“…Cariprazine is also approved in the US for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. 10 , 26 , 53 – 59 An active clinical development plan includes studies in bipolar I depression 60 and major depressive disorder. 61 …”

“…A pooled analysis of CGI-S scores examining shifts, such as from extremely or severely ill (CGI-S ≥5) to mildly ill or better (CGI-S ≤3), demonstrated an advantage for cariprazine over placebo (OR 3.4, 95% CI 1.5–7.9). 26 Of clinical relevance are observed effect sizes for antipsychotic response, as defined by change from baseline ≥30% in PANSS total score. 15 – 17 Pooling together data for the approved dose range of cariprazine (1.5–6 mg/day) revealed a number needed to treat (NNT) vs placebo of ten (95% CI 7–19); 11 however, in one trial the NNT vs placebo for response was as robust as six.…”

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

“…The CGI-S is a global measurement that uses informed clinical judgment to assess illness severity, level of distress and impairment, and the impact of the illness on functioning [ 56 ]. To better characterize the clinical relevance of cariprazine in improving disease severity in patients with schizophrenia, data from the three acute efficacy trials were pooled for post hoc analysis [ 57 ]. Cariprazine- and placebo-treated patients were categorized by baseline CGI-S scores and the proportion of patients who improved from more severe categories at baseline to less severe categories at study endpoint was evaluated.…”

Modern clinical pharmacology approaches to negative symptom treatment in schizophrenia

“…В исследованиях установлено, что именно D3-, а не D2-рецепторы играют особенно важную роль в регуляции настроения, чувства удовольствия, а также когнитивных функций. Дисфункция этих рецепторов сопряжена с депрессией, ангедонией и развитием когнитивных нарушений [16].…”

“…Карипразин был одобрен FDA в 2015 г. и затем European Medicines Agency (EMA) в 2017 г. для лечения шизофрении в дозировке 1,5-6 мг/сут [16]. В апреле 2019 года карипра-зин зарегистрирован в Республике Казахстан для лечения шизофрении.…”