1Meridien Research Inc.,Bradenton,Florida,USA.
2Allergan,Jersey City,New Jersey,USA.
CNS Spectr. 2018 Feb;23(1):39-50. doi: 10.1017/S1092852917000220. Epub 2017 May 8.
Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 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, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia.
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.
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.
Long-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.
卡利拉嗪是一种多巴胺 D3/D2 部分激动剂非典型抗精神病药物，对 D3 受体具有优先亲和力，已被批准用于治疗精神分裂症和双相 I 障碍相关的躁狂或混合发作。卡利拉嗪在三项针对精神分裂症急性加重患者的随机、双盲、安慰剂对照、6 周临床试验中已证实其疗效和安全性。本研究旨在评估卡利拉嗪治疗精神分裂症患者的长期安全性和耐受性。
这是一项多中心、开放性、灵活剂量的卡利拉嗪（3-9mg/d）治疗成人精神分裂症的研究。研究对象包括新患者和完成两项 III 期先导研究（NCT01104766、NCT01104779）的患者。符合条件的患者先进入为期最长达 1 周的无药物筛查期，随后接受为期 48 周的开放性、灵活剂量卡利拉嗪（3-9mg/d）治疗和 4 周安全性随访。
共 586 例患者接受开放性卡利拉嗪治疗，约 39%的患者完成了研究。未报告任何意外的安全性问题或死亡事件。最常见（≥10%）的不良事件（AE）为静坐不能（16%）、头痛（13%）、失眠（13%）和体重增加（10%）。59 例（10.1%）患者发生严重 AE，73 例（12.5%）患者因 AE 在开放性治疗期间停止研究。代谢、肝和心血管参数的平均变化被认为无临床意义。研究期间，平均体重增加 1.5kg，催乳素水平略有下降，疗效指标保持稳定。
在精神分裂症患者中，高达 9mg/d 的卡利拉嗪长期治疗似乎具有良好的安全性和耐受性。
