Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study

Abstract

Objective. Cariprazine, a dopamine D 3 /D 2 partial agonist atypical antipsychotic with preferential binding to D 3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebocontrolled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the longterm safety and tolerability of cariprazine in patients with schizophrenia.Methods. This was a multicenter, open-label, flexible-dose study of cariprazine 3-9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3-9 mg/d) and 4 weeks of safety follow-up.Results. A total of 586 patients received open-label cariprazine treatment, 39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable.Conclusions. Long-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia. Clinical Implications' Cariprazine was generally safe and well tolerated in patients with schizophrenia when flexibly dosed at 3-9 mg/d for up to 48 weeks of treatment.' The most common treatment-emergent adverse events (TEAEs) were akathisia, headache, insomnia, and weight gain. Most were mild or moderate in intensity and rarely resulted in discontinuation.' Mean changes in metabolic, cardiovascular, and laboratory parameters were generally small and not clinically significant. Prolactin levels decreased over the course of 48 weeks of treatment.' There were no unexpected safety issues or deaths in patients exposed to long-term cariprazine treatment in this study.' This study provides further evidence supporting the safety and tolerability of cariprazine for the long-term treatment of schizophrenia.

Possibilities of Partial D3-Receptor Agonists Usage in Addictive Pathology

“…Механизм действия В сентябре 2015 г. Управление по контролю качества пищевых продуктов и лекарственных средств США одобрило первый атипичный нейролептик третьей генерации -карипразин. Основная отличительная особенность данного класса нейролептиков -более высокая аффинность к D3-рецепторам, превышающая аффинность даже самого дофамина [3][4][5][6][7][8]. Следует напомнить, что центральные D3-рецепторы широ-ко представлены в коре больших полушарий и стволе головного мозга, но в основном сконцентрированы в лимбических областях и прилежащем ядре.…”

“…Возможно, это указывает на их регулирующую функцию дофаминергических сигналов в мезолимбической системе -ключевом нейроанатомическом субстрате развития психотической симптоматики при шизофрении, согласно дофаминовой гипотезе [4,7]. Кроме того, карипразин является частичным агонистом D2-рецепторов, как и представленные в настоящее время на рынке арипипразол и брекспипразол (последний в РФ не зарегистрирован), а также частичным агонистом рецептора серотонина 5-HT1A и антагонистом рецепторов 5-HT2B и 5-HT2A [8,9].…”

“…Кроме того, у больных в группе карипразина отмечалось более выраженное улучшение общего функционирования. Следовательно, снижение тяжести негативной симптоматики приводило к повышению уровня социальной адаптации [8,12,[25][26][27].…”

Relationship Between Plasma Concentrations and Clinical Effects of Cariprazine in Patients With Schizophrenia or Bipolar Mania

“…6 Cariprazine is approved for the treatment of adult patients with schizophrenia (United States and Europe; recommended dose range: 1.5-6 mg/day) and manic or mixed episodes associated with bipolar I disorder (United States; recommended dose range: 3-6 mg/day). Clinical trials included in the development programs for schizophrenia and bipolar mania have demonstrated the efficacy, safety, or tolerability of cariprazine in adult patients [7][8][9][10][11][12][13][14][15][16] ; in these studies, blood samples were collected for the measurement of plasma concentrations of cariprazine and its major metabolites.…”

Minimum Sample Size Requirements for a Validation Study of The Schizophrenia Quality of Life Scale-Revision 4 (SQLS-R4)

“…There are generic measures specifically designed for non-clinical populations exploring global concerns that are not necessarily unique to a schizophrenic population. On the other hand, specific measures such as the schizophrenic quality of life scale revision 4 (SQLS-R4, 6), has been identified as a particularly useful measure for understanding how symptoms of schizophrenia effect the patient's QoL (3,8,9). The SQLS-R4 is a self-report measure comprising 33 items from which two domains of QoL, psychosocial feelings (22 items, e.g.…”