FDA核准每月一次的Paliperidone Palmitate注射剂治疗精神分裂症

  美国食品药物管理局(FDA)核准一种长效、每月一次的paliperidone palmitate注射剂(商品名Invega Sustenna，Ortho-McNeil-Janssen Pharmaceuticals公司之子公司Janssen公司)，用於成人精神分裂症之急性与维持治疗。
　　
　虽然多数病患可以藉由持续的、长期抗精神病治疗来控制精神分裂症症状与復发风险，有大约80%的病患在诊断后5年内復发。復发风险增加原因之一为治疗不顺从性，服用口服抗精神病药物的病患经常有此状况。
　　
　Henry A. Nasrallah医师在公司的新闻稿中表示，药物顺从性不佳可以说是精神分裂症状控制障碍与復发风险的单一最大因素。核准每月一次的Invega Sustenn将可提供健康照护专业人士另一个治疗选择，同时，明确的持续药物顺从性监测工具也有助於精神分裂症的适当临床结果。
　　
　Nasrallah医师是Invega Sustenna临床试验的临床研究员，也是俄亥俄州辛辛那提大学医学院精神分裂症研究计画主任、精神与神经科学教授。
　　
　临床试验计画包括四个急性症状控制研究以及一个长期维持研究。四篇研究(n=1695人)显示，缓释型paliperidone注射剂对於改善精神分裂症病患之正向与负向症状量表(Positive and Negative Syndrome Scale，PANSS)整体分数显然比安慰剂更有效。
　　
　PANSS是一种多项目表单，可测量正向症状、负向症状、脱序思考、未控制的敌意/激动以及焦虑/忧鬱。
　　
　长期维持研究(n = 410人)的结果发现，缓释型paliperidone注射剂显著延迟了初次復发的时间(P < .0001)，相较於安慰剂，较少病患发生復发(10% vs 34%)。接受安慰剂病患的復发率为使用缓释型paliperidone palmitate者的3.6倍。此研究因为维持效果明确而提早停止。
　　
　使用paliperidone治疗者最常(发生率≧5%，发生率为安慰剂的2倍)报告的副作用为注射部位反应、想睡/镇静、头昏眼花、静坐不能(akathisia)、以及锥体外异常(extrapyramidal disorder)。
　　
　缓释型paliperidone palmitate治疗，在第1天，起始剂量应该是234 mg，1週之后为156 mg，注射部位都是在三角肌。建议的每月维持剂量维117 mg；根据病患的耐受性和/或效果，有些病患可能会需要比建议剂量高或低的剂量，剂量范围在39至234 mg。每月维持剂量可以注射在三角肌或臀肌。
 
FDA Approves Once-Monthly Paliperidone Palmitate Injection for Treating Schizophrenia

August 5, 2009 — The US Food and Drug Administration (FDA) has approved a long-acting, once-monthly formulation of paliperidone palmitate injection (Invega Sustenna, Janssen, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc) for the acute and maintenance treatment of schizophrenia in adults.

Although schizophrenic symptoms and the risk for relapse can be managed in most patients with continuous, long-term antipsychotic therapy, some 80% of patients relapse within 5 years of diagnosis. The risk for relapse increases as a result of therapeutic noncompliance, which is a common occurrence in patients receiving oral antipsychotics.

"Inconsistent compliance with medications is arguably one of the single greatest impediments to managing the symptoms of schizophrenia and delaying the time to relapse," said Henry A. Nasrallah, MD, in a company news release. "The approval of once-monthly Invega Sustenna will provide healthcare professionals with a treatment option that is, at the same time, a definitive monitoring tool for uninterrupted medication compliance, which may help optimize clinical outcomes in schizophrenia."

Dr. Nasrallah is a clinical investigator who worked on the Invega Sustenna clinical trials and a professor of psychiatry and neuroscience and director of the Schizophrenia Research Program at the University of Cincinnati College of Medicine, Ohio.

The clinical trial program consisted of 4 acute symptom control studies and 1 longer-term maintenance study. The 4 studies (n = 1695) demonstrated that extended-release paliperidone injection was significantly more effective than placebo for improving Positive and Negative Syndrome Scale (PANSS) total scores in schizophrenic patients.

PANSS is a multi-item inventory that measures positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression.

Results of the longer-term maintenance study (n = 410) revealed that extended-release paliperidone injection significantly delayed the time to first relapse (P < .0001), with fewer patients experiencing a relapse relative to placebo (10% vs 34%). Patients receiving placebo had a 3.6-fold higher rate of relapse compared with extended-release paliperidone palmitate. This study was stopped early because maintenance of efficacy was demonstrated.

Adverse events most commonly reported in paliperidone-treated patients (incidence ? 5% and occurring twice as often vs placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder.

Treatment with extended-release paliperidone palmitate should be initiated with a dose of 234 mg on treatment day 1 and then 156 mg 1 week later, with both injections administered in the deltoid muscle. The recommended monthly maintenance dose is 117 mg; some patients may benefit from lower or higher maintenance doses within the recommended range of 39 to 234 mg based on individual tolerability and/or efficacy. Monthly maintenance doses can be administered in either the deltoid or gluteal muscle.