Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
Clin Drug Investig. 2012 Aug 1;32(8):497-512. doi: 10.2165/11634440-000000000-00000.
Paliperidone, 9-hydroxy-risperidone, is the major metabolite of the atypical antipsychotic risperidone and is available in an oral extended-release (ER) formulation. Paliperidone ER was approved for treating schizophrenia in 2006, and in 2009 it became the first atypical antipsychotic licensed for treating schizoaffective disorder. The short-term efficacy, safety and tolerability of paliperidone ER for patients with schizophrenia were demonstrated in three pivotal 6-week, randomized, double-blind, placebo-controlled studies. Data from the long-term trial showed that paliperidone ER is also effective in preventing relapse of schizophrenia. Two randomized, placebo-controlled, short-term studies have documented the efficacy and tolerability of paliperidone ER in the treatment of schizoaffective disorder, but no long-term or maintenance study has been conducted in patients with schizoaffective disorder. Two 3-week, randomized, double-blind, placebo-controlled studies showed that paliperidone ER is significantly superior to placebo for treating patients with bipolar disorder, but the results were driven by certain subpopulations. Limited evidence suggests that paliperidone ER can potentially be superior to quetiapine and risperidone. However, few direct head-to-head comparisons between paliperidone ER and other antipsychotics have been conducted to confirm these results. The distinctive pharmacological characteristics of paliperidone ER, including smooth fluctuations in plasma drug concentrations, predominantly renal excretion, low risk of causing hepatic impairment and low drug-drug interaction, might provide important clinical advantages compared with risperidone. However, certain side effects require clinical attention. The rate of extrapyramidal side effects was considerably higher than that of a placebo at doses ≥9 mg/day. The risks for orthostatic hypotension, prolongation of the corrected QT interval and hyperprolactinaemia are also concerns. This review summarizes the currently published data on paliperidone ER for treating patients with schizophrenia, schizoaffective disorder and bipolar disorder, and suggests its appropriate use in clinical practice.
帕利哌酮、9-羟基利培酮，是一种新型抗精神分裂症药物利培酮的主要代谢产物，目前已上市一种口服延长释放剂型。帕利哌酮延长释放剂型于 2006 年被批准用于治疗精神分裂症，2009 年成为第一个获准用于治疗分裂情感性障碍的非典型抗精神病药物。三项为期 6 周的关键性、随机、双盲、安慰剂对照研究证实了帕利哌酮延长释放剂型治疗精神分裂症患者的短期疗效、安全性和耐受性。长期试验数据表明，帕利哌酮延长释放剂型也可有效预防精神分裂症复发。两项随机、安慰剂对照、短期研究记录了帕利哌酮延长释放剂型治疗分裂情感性障碍的疗效和耐受性，但在分裂情感性障碍患者中尚未开展长期或维持治疗研究。两项为期 3 周的随机、双盲、安慰剂对照研究显示，帕利哌酮延长释放剂型在治疗双相障碍患者方面明显优于安慰剂，但结果是由某些亚人群驱动的。有限的证据表明，帕利哌酮延长释放剂型在某些方面可能优于喹硫平和利培酮。然而，尚未开展帕利哌酮延长释放剂型与其他抗精神病药物的直接头对头比较研究来证实这些结果。与利培酮相比，帕利哌酮延长释放剂型具有独特的药理学特征，包括药物浓度在血浆中平稳波动、主要经肾脏排泄、导致肝损伤的风险低、药物相互作用低，这可能为临床带来重要优势。然而，某些副作用需要临床关注。与安慰剂相比，剂量≥9mg/天时，锥体外系副作用的发生率明显更高。体位性低血压、校正 QT 间期延长和高催乳素血症的风险也令人担忧。本综述总结了目前已发表的关于帕利哌酮延长释放剂型治疗精神分裂症、分裂情感性障碍和双相障碍患者的相关数据，并就其在临床实践中的合理应用提出建议。
