帕利哌酮棕榈酸盐的临床研究进展

帕利哌酮棕榈酸盐是一种非典型抗精神病药物的长效针剂,活性成分为帕利哌酮,也称9-羟利培酮,主要通过阻断5-羟色胺2A受体和多巴胺D2受体发挥抗精神病药作用。该药在制备过程中采用了特殊的纳米晶体技术,有效提高药物溶解度,使得药物在使用过程中更加安全有效。经试验证实,帕利哌酮棕榈酸盐对精神分裂症急性期治疗和维持治疗效果较好,与现有长效针剂相比具有一定优势,为精神分裂症患者的治疗提供了一种新的选择。     

抗精神分裂症药帕利哌酮研究进展

帕利哌酮为抗精神失常药利哌酮的主要活性代谢物,为非典型性抗精神病药.本品是一种完全5-羟色胺(HT)2受体和部分多巴胺D2受体的拮抗剂.临床试验结果显示,本品能够有效地改善急性精神分裂症患者的症状,延缓精神分裂症复发以及改善患者睡眠状况.本品由强生公司子公司杨森公司开发,商品名INVEGATM,为帕利哌酮缓释片.2006年12月20日美国FDA批准其用于治疗精神分裂症,是2003年以来FDA批准的首个治疗精神分裂症的处方药[1].强生公司已向欧盟提出上市申请,目前本品在我国已获药品行政保护.本文从释药系统、药效学、药代动力学、临床研究、不良反应等方面对帕利哌酮研究进展进行综述.     

帕利哌酮缓释片与利培酮口服液治疗精神分裂症和分裂样精神病患者临床分析

目的:探索分析应用帕利哌酮缓释片以及利培酮口服液针对精神分裂症以及分裂样精神病患者实施治疗的不同作用和效果.方法:将我院收治的精神分裂症以及分裂样精神病患者作为研究对象开展分组研究,对照组按照常规方式均实施利培酮口服液治疗,研究组实施帕利哌酮缓释片治疗.将临床效果进行对比.结果:完成治疗后,研究组PANSS评分明显低于对照组以及治疗前(P＜0.05),PSP评分均明显超过对照组以及治疗前(P＜0.05);在不良反应方面,两组相对接近(P＞0.05).结论:针对精神分裂症以及分裂样精神病患者选用帕利哌酮缓释片进行治疗,可以有效改善患者的临床症状,对于促进其预后具有积极意义.     

帕利哌酮缓释片与利培酮治疗精神分裂症和分裂样精神病的对照研究

目的：观察帕利哌酮缓释片（芮达）与利培酮治疗精神分裂症和分裂样精神病临床疗效、社会功能差异。方法：82例符合诊断标准的精神分裂症或精神分裂样精神病患者被随机分为帕利哌酮缓释片组（n=42）与利培酮组（n=40）进行4周的治疗和观察,在治疗后第1周末、第2周末、第3周末、第4周末比较两组之间阳性与阴性症状量表（PANSS）减分率、临床疗效总评量表（CGI）减分率和个体和社会功能量表（PSP）分值的差异。结果：PANSS减分率,帕利哌酮缓释片组在治疗后第1周末、第2周末、第3周末、第4周末均明显高于利培酮组,差异有统计学意义（P〈0.05）;治疗后第4周末,CGI减分率帕利哌酮缓释片组明显高于利培酮组,差异有统计学意义（P〈0.05）;PSP分值,帕利哌酮缓释片组在治疗后第1周末、第2周末、第3周末、第4周末均明显高于利培酮组,差异有统计学意义（P〈0.01）。结论：帕利哌酮缓释片可以明显改善精神分裂症和分裂样精神病患者的精神病性症状及社会功能。     

帕利哌酮临床安全性研究进展

帕利哌酮是较新的非典型抗精神病药物之一,是利培酮的活性代谢产物9-羟利培酮,主要通过拮抗多巴胺(D2)受体和5羟色胺(5-HT2A)受体发挥抗精神病的治疗作用。帕利哌酮易产生不良反应包括EPS反应、泌乳素水平升高等不良反应,本文综述了近几年帕利哌酮安全性方面的临床研究和不良反应的处理,为帕利哌酮的合理应用提供更好的方案,给临床医生提供更多的参考。     

帕利哌酮缓释片与奥氮平治疗精神分裂症患者的对照研究

目的:比较帕利哌酮缓释片与奥氮平治疗精神分裂症患者的疗效和安全性。方法:对156例精神分裂症患者随机分成帕利哌酮缓释片组和奥氮平组。采用简明精神病评定量表(BPRS)和不良反应症状量表(TESS),于治疗前、治疗1周、2周、4周和8周分别评定疗效和不良反应。结果:帕利哌酮缓释片组和奥氮平组的有效率分别为68.75%和65.78%,无显著差异。帕利哌酮缓释片组起效快,治疗1周后BPRS评分即显著下降,与奥氮平组有显著性差异(P<0.05),治疗8周后BPRS评分差异也有统计学意义(P<0.05)。帕利哌酮缓释片组不良反应轻微且低于奥氮平组。帕利哌酮组常见不良反应(发生率≥5%)为泌乳、闭经和便秘;奥氮平组(发生率≥5%)常见不良反应主要为镇静嗜睡、体重增加、血糖异常、头昏、便秘和转氨酶升高。结论:帕利哌酮缓释片与奥氮平对改善精神分裂症患者的有效率相当,但帕利哌酮缓释片起效迅速,不良反应少且轻微。     

帕利哌酮缓释片临床用药指导意见

精神分裂症是一组病因未明的精神疾病,其病程迁延,易慢性化,多数患者会出现精神残疾。目前的治疗目标不仅是控制症状,还要改善患者的社会功能。文中综述了帕利哌酮缓释片的药理特点,并就其临床使用提出指导意见。帕利哌酮缓释片是一种新型第二代抗精神病药,其有效成分帕利哌酮是利培酮的活性代谢产物,同时OROS控释技术可以带来平稳的血药浓度。帕利哌酮缓释片起效迅速,能够全面有效控制症状,安全性良好,同时可以显著改善患者的社会功能。     

自然状态帕利哌酮缓释片治疗精神分裂症患儿的疗效和安全性研究及用药建议

目的:探讨帕利哌酮缓释片对精神分裂症住院患儿的疗效及安全性,提出利培酮滴定渐换帕利哌酮缓释片以及其他抗精神病药渐换帕利哌酮缓释片的用药建议。方法:入组2009年6月-2011年7月入住我院、接受口服帕利哌酮缓释片治疗、疗程满12周的所有精神分裂症患儿,共55例。帕利哌酮缓释片采用利培酮滴定逐渐加量方法,在基线时及治疗后第2,4,6,8,10和12周末应用阳性与阴性症状量表(PANSS)评定疗效,使用不良反应量表(TESS)评价安全性,并于基线和治疗后第4,8和12周进行血常规、血生化、泌乳素、心电图检查,每周进行生命体征及体重测量。结果:全部患儿加药过程顺利,没有患儿因为帕利哌酮缓释片加量而出现耐受性问题。自第2周开始单用组、合用或换用帕利哌酮缓释片组PANSS总分、阳性量表分、阴性量表分、一般精神病理量表分均低于基线,差异均具有显著性意义(P<0.05)。单用组、合用或换用组均未见严重不良反应。单用组对体重影响较小,两组对泌乳素的影响无统计学差异。结论:帕利哌酮缓释片可有效改善精神分裂症患儿的阳性症状、阴性症状,安全性高,适合青少年精神分裂症的治疗。在青少年中使用时可尝试采用利培酮滴定逐渐换用和增加帕利哌酮缓释片剂量的方法。     

口服帕利哌酮缓释片对精神分裂症患者心电图影响的调查分析

目的 观察口服帕利哌酮缓释片对精神分裂症患者心电图的影响。方法 55例精神分裂症患者,口服帕利哌酮缓释片,观察服药前后心电图变化。结果 患者服药后第1、2、3个月心电图异常发生率比较,差异无统计学意义（P〉0.05）。心电图异常与性别、药物剂量、年龄和病程的关系比较,差异无统计学意义（P〉0.05）。结论 帕利哌酮缓释片对心脏的影响较小,作为新型的抗精神病药物,心脏毒性较小,值得推广。     

帕利哌酮缓释片治疗精神分裂症疗效观察

目的探讨帕利哌酮缓释片治疗精神分裂症的临床效果。方法将126例精神病患者按照随机数字表法分为治疗组和对照组,每组63例,治疗组给予帕利哌酮,起始剂量为6 mg/d,并根据病情2周内调整药量;对照组给予奥氮平,起始剂量为5～10 mg/d,并根据病情2周内调整剂量,均为口服治疗,1次/d,给药8周,观察和记录治疗效果,并对结果进行分析。结果治疗组痊愈4例,显效37例,好转14例,无效8例,总有效率为87.3%;对照组组痊愈2例,显效36例,好转15例,无效10例,总有效率为84.1%;两组总疗效比较差异有统计学意义(P>0.05)。结论帕利哌酮缓释片用于治疗精神分裂症患者耐受性好,不良反应轻,可有效的改善患者阳性症状和阴性症状,值得临床推广应用。     

新型抗精神病药帕利哌酮缓释片的临床研究进展

帕利哌酮缓释(paliperidone ER)片是于2009年在国内上市的一种新型抗精神病药物。本文比较了帕利哌酮与利培酮在药理学特性和作用机制方面的区别,对帕利哌酮与其他非典型抗精神病类药物如利培酮、喹硫平、奥氮平、阿立哌唑在临床应用以及不良反应等方面的对照研究进展进行了综述。     

Paliperidone: a new extended-release oral atypical antipsychotic

Paliperidone extended release (ER) is the most recent atypical antipsychotic to become available for the treatment of schizophrenia. It has a unique extended-release delivery system, allowing once/day dosing with steady plasma concentrations of the medication. Several randomized, double-blinded, placebo-controlled trials have shown paliperidone ER to be efficacious in the management of acute schizophrenia as well as for the prevention of symptom recurrence when compared with placebo. Patients in the treatment groups receiving daily doses ranging from 3 to 12 mg displayed generalized symptom improvement using the Positive and Negative Syndrome Scale (PANSS) and improved functioning on the Personal and Social Performance Scale. Paliperidone ER has been shown to be generally safe and tolerable. At its recommended dose of 6 mg daily, the reported extrapyramidal symptom adverse events are similar to placebo, and weight gain is very modest. However, at higher doses, weight gain and extrapyramidal symptoms are more elevated. Paliperidone ER has the potential to offer advantages over its parent compound and other second generation agents, and may aid in ensuring compliance among persons with schizophrenia. At present, there are no published data from a comparative trial with paliperidone ER versus its parent compound or other second-generation antipsychotic agents.     

Paliperidone: a new extended-release oral atypical antipsychotic

Paliperidone extended release (ER) is the most recent atypical antipsychotic to become available for the treatment of schizophrenia. It has a unique extended-release delivery system, allowing once/day dosing with steady plasma concentrations of the medication. Several randomized, double-blinded, placebo-controlled trials have shown paliperidone ER to be efficacious in the management of acute schizophrenia as well as for the prevention of symptom recurrence when compared with placebo. Patients in the treatment groups receiving daily doses ranging from 3 to 12 mg displayed generalized symptom improvement using the Positive and Negative Syndrome Scale (PANSS) and improved functioning on the Personal and Social Performance Scale. Paliperidone ER has been shown to be generally safe and tolerable. At its recommended dose of 6 mg daily, the reported extrapyramidal symptom adverse events are similar to placebo, and weight gain is very modest. However, at higher doses, weight gain and extrapyramidal symptoms are more elevated. Paliperidone ER has the potential to offer advantages over its parent compound and other second generation agents, and may aid in ensuring compliance among persons with schizophrenia. At present, there are no published data from a comparative trial with paliperidone ER versus its parent compound or other second-generation antipsychotic agents.     

Paliperidone extended release

Paliperidone extended release (ER) is an atypical antipsychotic that is administered orally once daily to provide consistent plasma drug concentrations over 24 hours in adult patients with schizophrenia. In four well controlled trials, once-daily administration of paliperidone ER 3-12 mg over 6 weeks was more effective than placebo in reducing the positive and negative symptoms experienced by adult patients with schizophrenia, including elderly individuals aged > or =65 years. Patients with schizophrenia treated with paliperidone ER achieved greater improvement in clinically relevant measures of personal and social functioning and disease severity than those who received placebo. In another well controlled trial, paliperidone ER demonstrated superior efficacy to placebo in preventing the recurrence of schizophrenia symptoms. In patients who experienced a recurrence, time to recurrence was delayed with paliperidone ER compared with placebo administration.black triangle Paliperidone ER 3-12 mg/day for 6 weeks was generally well tolerated by patients with schizophrenia in clinical trials.     

Profile of paliperidone extended release: review of efficacy and safety data

Paliperidone, an active metabolite of risperidone, is the most recent second-generation antipsychotic to become available on the market. This article addresses the pharmacology, clinical efficacy and tolerability of paliperidone. A comprehensive review of studies on MEDLINE using terms, such as paliperidone, 9-hydroxy risperidone, efficacy and tolerability, was conducted. Paliperidone, a 9-hydroxy derivative of risperidone is an antagonist at the dopamine and serotonin receptor sites. As paliperidone is an active metabolite of the parent compound risperidone, it is not metabolized hepatically, has minimal drug–drug interactions and is largely excreted unchanged by the kidneys. It follows linear pharmacokinetics. Evidence from short- and long-term trials supports the efficacy and tolerability of paliperidone extended release (ER) in the treatment of schizophrenia. Randomized, double-blind, placebo-controlled, multicenter studies have demonstrated both paliperidone 6 and 12 mg result in symptom improvement, increase in time of first recurrence of psychotic symptoms as well as significant improvements in personal and social performance. Studies demonstrated increases in plasma prolactin levels and extrapyramidal symptoms with paliperidone ER treatment compared with placebo. Changes in blood glucose and lipid levels with paliperidone ER were comparable to placebo. Overall, paliperidone is an efficacious, well-tolerated addition to the treatment armamentarium for schizophrenia.     

A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia

The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.     

Paliperidone extended-release: a review of efficacy and tolerability in schizophrenia,schizoaffective disorder and bipolar mania

Importance of the field: Paliperidone extended-release (ER), a once-daily, oral, atypical antipsychotic, has been available in the USA and the EU for the treatment of schizophrenia for more than 2 years and was recently (July 2009) approved in the USA for treatment of schizoaffective disorder. Additional data on its efficacy and safety, including that for additional indications, is emerging.

Areas covered in this review: This review provides a background on the compound and summarizes recent data available on treatment of schizophrenia, including comparative data with other antipsychotics, and efficacy and safety data from clinical trials in schizoaffective and bipolar disorders.

What the reader will gain: The reader will gain knowledge of the compound and the existing clinical data so far for paliperidone ER.

Take home message: Paliperidone ER is effective for the treatment of schizophrenia and is at present the only antipsychotic approved in the USA for treatment of schizoaffective disorder. Its efficacy and tolerability profile in treating patients with schizophrenia or schizoaffective disorder indicates that paliperidone ER offers an important treatment option among atypical antipsychotic therapy for these patients.     

Paliperidone extended-release for the treatment of schizophrenia

Paliperidone, the major active metabolite of risperidone (9-hydroxyrisperidone), is a second-generation antipsychotic that was recently approved by the United States Food and Drug Administration for treatment of acute schizophrenia and for maintenance treatment of schizophrenia. We performed a literature search of PreMEDLINE, MEDLINE, and International Pharmaceutical Abstracts from 1966-October 2007 to review the available data on the pharmacology, pharmacokinetics, clinical evidence, and safety and tolerability profile of paliperidone extended-release (ER). Articles from randomized controlled trials, abstracts, and posters presented at national scientific meetings were included in this review. Paliperidone ER has been shown to be significantly more effective in improving schizophrenic symptoms according to the Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions-Severity Scale, and Personal and Social Performance Scale compared with placebo (p<0.05). In addition, limited evidence suggests similar efficacy between paliperidone ER 6-12 mg/day and risperidone 4-6 mg/day. A 2-week, double-blind comparison with quetiapine demonstrated that paliperidone ER was significantly better than quetiapine in improving PANSS scores (p<0.001). Paliperidone ER appears to be well tolerated at the recommended starting dosage of 6 mg/day. The most commonly reported adverse effect was dose-related extrapyramidal symptoms. Weight gain and metabolic disturbances were minimal. The cost of paliperidone ER appears to be slightly higher than that of other second-generation antipsychotics. Paliperidone ER tablets may be a safe and effective treatment option for acute schizophrenia and maintenance treatment of schizophrenia compared with placebo. Because well-designed comparative data are lacking, an additional benefit over other antipsychotics is yet to be determined.     

Paliperidone: a review of clinical trial data and clinical implications

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.