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.     

帕利哌酮与利培酮治疗精神分裂症的疗效和安全性Meta分析

目的 评价帕利哌酮与利培酮治疗精神分裂症疗效和安全性的差异。方法 应用循证医学方法对符合标准的16项研究进行分析,评价帕利哌酮与利培酮治疗精神分裂症过程中有效率、治疗后量表评分及不良反应等的差异。结果 帕利哌酮与利培酮治疗精神分裂症的有效率和治疗后量表评分的差异均有统计学意义;两者治愈率差异无统计学意义;帕利哌酮组锥体外系反应、失眠、泌乳及月经紊乱、肝功能异常的发生率明显低于利培酮组,两者具有显著性统计学差异。结论 帕利哌酮疗效优于利培酮,不良反应的发生率明显低于利培酮。     

帕利哌酮缓释片治疗儿童期首发精神分裂症37例的疗效及安全性

目的:探讨帕利哌酮缓释片治疗儿童期首发精神分裂症患者临床疗效及安全性。方法:对37例儿童期首发精神分裂症患者应用帕利哌酮缓释片治疗,观察6个月。采用阳性与阴性症状量表(PANSS)、个人和社会功能量表(PSP)评定临床疗效,并通过治疗满意度调查问卷(MSQ)调查治疗满意度;采用副反应量表(TESS)评定不良反应,并进行实验室监测。结果:观察结束时总有效率为86.5%;PANSS总分、阳性症状分量表、一般精神病理分量表评分于治疗4 d起较治疗前有所下降(P<0.05),于治疗1周末、2周末、3月末、6月末,均较治疗前有显著下降(P<0.01);阴性症状分量表评分于治疗1周时有所下降(P<0.05),于治疗2周末、3月末、6月末,均较治疗前有显著下降(P<0.01)。不良反应轻微,多可自行缓解。社会功能明显改善,治疗满意度为81.1%。结论:帕利哌酮缓释片治疗儿童期首发精神分裂症患者起效快,疗效确切,不良反应轻微,安全性高,依从性好。     

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。     

Clozapine for the treatment of schizophrenia

Introduction: Despite considerable progress in the pharmacological treatment of schizophrenia, about 30% of patients are minimally responsive to antipsychotics and there is still an excessively high rate of mortality in schizophrenia patients. Clozapine, a D₂-5HT₂ antagonist, was the first antipsychotic to demonstrate efficacy in treatment-resistant patients, and to be associated with the lowest risk of death.

Areas covered: The pharmacodynamics, pharmacokinetics, clinical efficacy, safety and cost-effectiveness of clozapine are covered in this article, based on a literature review (PubMed) from 1975 to 2012. Pivotal, as well as supporting, randomized controlled trials are reviewed, along with observational and/or naturalistic safety studies. This review of clozapine will allow the reader to determine the place for clozapine in the schizophrenia treatment landscape. Expert opinion: Studies conducted so far suggest that clozapine is the treatment of choice for schizophrenic patients who are refractory to treatment, display violent behaviors, or who are at high risk of suicide. However, it is also the antipsychotic with the worst side effect profile, the highest risk of complications, and the most difficult to prescribe. Experience with clozapine should therefore be included in the education of future physicians.     

可变剂量帕利哌酮缓释片治疗急性期精神分裂症的疗效及对糖脂代谢的影响

目的:研究可变剂量帕利哌酮缓释片治疗急性期精神分裂症的有效性、耐受性及其对糖脂代谢的影响。方法:采用开放、单组研究,使用可变剂量(3～12 mg)帕利哌酮缓释片治疗急性期精神分裂症患者,为期8周。使用阳性与阴性症状量表(positive and negative syndrome scale,PANSS)评价有效性,治疗后较基线减分率≥30%为有效,同时比较治疗后PANSS总分及各分量表得分较基线的差异。测量血压、腹围、空腹血糖(fsat plasma glucose,FPG)、总胆固醇(total cholesterol,TG)及三酰甘油(triglyceride,TC),比较治疗后与基线的差异。结果:符合入组标准患者55例,最终纳入有效统计为48例。治疗8周末的有效率为79.17%,PANSS总分与基线相比有统计学意义(P<0.01)。治疗终点时45.83%患者的剂量为9 mg.d-1,43.75%为6 mg.d-1,2.08%的患者因不能耐受而下调剂量至3 mg.d-1。患者腹围在治疗8周末较基线增加(P<0.01)。血糖、血压及总胆固醇无明显变化。结论:可变剂量帕利哌酮缓释片治疗急性期分裂症有效,耐受性好,对糖脂代谢影响有待进一步研究。     

Asenapine review,part II: clinical efficacy,safety and tolerability

Introduction: Asenapine is a second-generation (atypical) antipsychotic currently marketed for the treatment of schizophrenia and bipolar mania/mixed episodes.

Areas covered: The purpose of this review is to describe the clinical profile of asenapine.

Expert opinion: Asenapine's efficacy in the treatment of schizophrenia and in the acute management of bipolar manic or mixed episodes, within the recommended therapeutic dose range of 5 – 10 mg twice a day, is evidenced by a broad clinical development program. Asenapine's overall tolerability profile is notable for the potential for sedation (time-limited) and, to a lesser extent, extrapyramidal symptoms/akathisia, dizziness, and oral hypoesthesia. Asenapine's effects on weight and metabolic variables appear modest, as are its effects on the ECG QTc interval and on prolactin.     

Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidone

A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n = 43); olanzapine (n = 66); or risperidone (n = 55) monotherapy. Patients were initiated with quetiapine to 400 mg/day over 7 days, and then flexibly dosed (300-750 mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138) mg/day in the haloperidol subgroup, 472 (147) mg/day in the olanzapine subgroup and 485 (141) mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of -32.5, -15.4, and -18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p < 0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p < 0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p < 0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone.     

帕利哌酮缓释片治疗精神分裂症患者的血药浓度与临床疗效

目的 探讨帕利哌酮缓释片治疗精神分裂症患者的血药浓度与临床疗效的相关性。方法 选择2014年9月—2017年8月在新乡医学院第二附属医院诊治的101例精神分裂症患者,给予帕利哌酮缓释片治疗,在治疗第2、4、8周进行帕利哌酮血药浓度检测,同时进行临床疗效、不良反应的判定与记录。结果 101例患者的帕利哌酮缓释片平均口服剂量为（6.30±0.98）mg/d,平均血药浓度为（31.90±14.29）ng/mL,治疗第2、4、8周的服药剂量与血药浓度对比无显著差异。治疗第2、4、8周的有效率分别为82.2%、92.1%、98.0%,对比差异显著（P<0.05）。治疗第2、4、8周的不良反应发生率分别为8.9%、9.9%、10.9%,对比无显著差异。Spearman非参数相关分析显示帕利哌酮的血药浓度与临床疗效有效率间无显著相关性（r=0.154）;治疗第8周,发生不良反应的患者血药浓度明显高于未发生不良反应（P<0.05）。结论 帕利哌酮缓释片治疗精神分裂症有很好的治疗效果,随着帕利哌酮缓释血药浓度的增加,临床疗效无显著增加,但是可增加不良反应发生率,需要合理调整用药剂量。     

帕利哌酮缓释片和利培酮对首发精神分裂症患者认知功能的影响

目的:探讨帕利哌酮缓释片与利培酮对首发精神分裂症患者认知功能的影响。方法:50例首发精神分裂症患者随机分为帕利哌酮缓释片组(n=25)和利培酮组(n=25),均单药治疗。在治疗前和治疗8周末采用阳性和阴性症状量表(PANSS)、威斯康星分类卡片测验(WCST)、连续作业测验(CPT)、数字划销测验(CT)及修订韦氏成人记忆量表(WMS-R)评价临床疗效及认知功能。结果:治疗后两组PANSS总分及各因子评分均较治疗前显著下降,差异有统计学意义(P<0.01);帕利哌酮缓释片组有效率为80%,利培酮组有效率为76%,两组相比差异无统计学意义。治疗前后帕利哌酮缓释片组WCST,CPT,CT及WMS-R各项指标比较差异有统计学意义(P<0.05,P<0.01),利培酮组仅WCST及WMS-R指标比较差异有统计学意义(P<0.05);治疗8周末两组间各项观察指标比较差异无统计学意义。结论:帕利哌酮缓释片治疗首发精神分裂症疗效和利培酮相当,对于认知功能的改善总体相似,但在执行功能和注意力方面帕利哌酮缓释片略优于利培酮。     

A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p⩽0.006) and PANSS negative and positive symptom Marder factor scores (p⩽0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.     

中国HIV-1患者使用利匹韦林为基础抗病毒方案的长期疗效和安全性及耐受性

目的:评估利匹韦林(rilpivirine,RPV)联合2种核苷类逆转录酶抑制剂(NRTIs)对中国HIV-1型感染者的长期安全性、耐受性和疗效.方法:本研究为RPV开放多中心Ⅲ期延长研究TMC278-TiDP6-C222的中国亚组分析,入组患者在既往RPV Ⅱb和Ⅲ期研究结束后签署知情同意自愿纳入延长研究,继续接受R...     

帕利哌酮缓释片治疗老年精神分裂症30例

目的观察帕利哌酮治疗老年精神分裂症的疗效及安全性。方法对30例老年精神分裂症患者给予帕利哌酮治疗8周,采用阳性和阴性症状量表、不良反应量表评价疗效及不良反应。结果帕利哌酮具有良好的疗效,8周末显效率为60.00%,有效率为90.00%,不良反应主要为锥体外系反应、失眠、心动过速。结论帕利哌酮治疗老年精神分裂症疗效确切,不良反应少。     

帕利哌酮对精神分裂症患者社会功能影响的随机开放对照研究

目的探讨帕利哌酮治疗精神分裂症患者的疗效及对社会功能的影响。方法 92例精神分裂症患者随机分为研究组(帕利哌酮组,47例,剂量3～12 mg.d-1)和对照组(利培酮组,45例,剂量1～6 mg.d-1),观察12 wk。于基线、治疗wk 8、wk 12末分别采用阳性与阴性症状量表(PANSS)、个人和社会功能量表(PSP)、药物治疗满意度调查问卷(MSQ)以及治疗时出现的症状量表(TESS)进行临床评定,并检测相关的实验室指标等。结果至研究终点,研究组总有效率与对照组相似(64%vs.60%,P>0.05)。2组在治疗wk 8、wk 12末的PANSS总分及各因子分、PSP总分较基线有明显改善(P<0.05)。研究组在治疗wk 12末的PANSS总分及各因子分较治疗wk 8末有下降(P<0.05)、PSP总分有升高(P<0.05),而对照组无显著变化。2组均未出现严重不良反应,而研究组不良反应发生率相对较低(P<0.05)。研究组药物治疗满意度更好(72%vs.51%,P<0.05)。结论帕利哌酮能有效改善精神分裂症患者的精神症状和社会功能。     

Drug safety in acute migraine treatment

Introduction: A number of drugs are available for acute migraine treatment, but they are not all effective for all patients and all attacks. The safety profiles of migraine drugs limit their use in patients with certain comorbid conditions, and adverse effects may also reduce the level of patient compliance.

Areas covered: The different types of acute migraine drugs are discussed, with particular regard to safety issues and potential adverse effects. The frequent use of analgesics, ergot alkaloids and triptans may result in the development of medication overuse headache (MOH).

Expert opinion: The initiation of a migraine attack is not fully understood, and therefore treatment aimed at causative factors is currently not available. The tolerability and adverse effects of the drugs available at present often limit their use. NSAIDs are frequently associated with gastrointestinal, and possibly also cardiovascular side effects. Ergot alkaloids may induce arterial vasoconstriction, while the administration of triptans is contraindicated in cardiovascular, cerebrovascular and peripheral vascular diseases. The frequent use of these drugs poses the risk of the development of MOH. There is a need for pathomechanism-based drugs, and for the future achievement of personalized medicine.