Weight gain and antipsychotics: a drug safety review

Introduction: Second-generation antipsychotics (SGAs) are widely used in several psychiatric disease entities and exert to a different extent a risk for antipsychotic-induced weight gain (AIWG). As AIWG is associated with an increase in metabolic syndrome or cardiovascular events, knowledge of these risks is crucial for further monitoring and the initiation of counteractive measures.

Areas covered: We searched PubMed and Web of Sciences for randomized-controlled trials and naturalistic observational studies published between 2010 and 2014 with sample sizes exceeding 100, including all marketed SGAs apart from zotepine, and providing data on weight increase. We also summarized relevant systematic reviews and meta-analyses of head-to-head comparisons.

Expert opinion: Recently published data still support the hierarchical ranking of SGAs already proposed in previous reviews ranking clozapine and olanzapine as having the highest risk, followed by amisulpride, asenapine, iloperidone, paliperidone, quetiapine, risperidone and sertindole in the middle, and aripiprazole, lurasidone and ziprasidone with the lowest risk. Number needed to harm varied considerably in our meta-analysis. Younger patients and patients with a lower baseline body mass index are most vulnerable. The greatest amount of weight gain occurs within the first weeks of treatment. AIWG occurs in all diagnostic groups and is also common in treatment with first-generation antipsychotics; therefore, awareness of this adverse event is essential for anyone prescribing antipsychotics.     

帕利哌酮缓释片与利培酮对男性急性精神分裂症患者社会功能的影响

目的：探讨帕利哌酮缓释片与利培酮治疗男性急性精神分裂症患者的临床疗效和安全性,以及对社会功能影响。方法将80例男性急性精神分裂患者随机分为两组,每组40例,研究组口服帕利哌酮缓释片治疗,对照组口服利培酮治疗,观察12周。治疗前后采用阳性与阴性症状量表评定临床疗效,个人和社会功能量表评定社会功能,副反应量表评定不良反应。结果治疗12周末两组阳性与阴性症状量表总分及各因子分均较治疗前显著下降（ P＜0．01）,研究组较对照组下降更显著（P＜0．01）;两组个人和社会功能量表总分较治疗前显著升高（P＜0．01）,研究组较对照组升高更显著（ P＜0．01）;研究组总有效率为85．0％,对照组为75．0％,两组比较差异无显著性（χ2＝2．54,P＞0．05）;研究组不良反应发生率为20．0％,对照组为42．5％,研究组不良反应发生率显著低于对照组（χ2＝4．71,P＜0．05）。结论帕利哌酮缓释片与利培酮均能有效改善男性急性精神分裂症患者的各种精神症状和社会功能,但帕利哌酮缓释片改善社会功能方面优于利培酮,安全性更高。     

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。     

帕利哌酮缓释片对酒精所致精神病性障碍患者精神症状及生活质量的疗效观察

目的 探讨帕利哌酮缓释片对酒精所致精神病性障碍患者精神症状及生活质量的疗效及安全性。方法 收集50例酒精所致精神病性障碍患者,随机分为研究组和对照组,研究组使用帕利哌酮缓释片,对照组使用氟哌啶醇片,研究时间为6周,运用阳性与阴性症状量表(PANSS)、生活质量指数问卷(QL-Index)和副反应量表(TESS)对2组患者进行疗效及不良反应的评定。结果 研究组有效率为72%,显著高于对照组的60%(P<0.05)。研究组PANSS评分在入组后第1周较入组时有显著性下降,QL-Index评分在入组后第1周较入组时有显著提高(P<0.05)。与对照组相比,研究组PANSS评分在入组后第1周阳性分及总分显著降低,在入组后第2,4,6周时阳性分、阴性分及总分均显著降低(P<0.05);QL-Index评分在入组后第1,2,4,6周时均显著升高;研究组TESS评分在入组后第1,2,4,6周时均显著降低。结论 帕利哌酮缓释片在改善酒精所致精神病性障碍患者精神症状、生活质量及安全性等方面优于氟哌啶醇。     

精神分裂症超高危人群、首发患者认知功能与精神病理症状的相关性及帕利哌酮的干预作用

目的：探讨精神分裂症患者各个阶段认知功能的特点及与精神病病理症状的相关性,并研究帕利哌酮的干预作用。方法运用持续操作测验（CPT）和 Stroop 色词测验对满足入组标准的超高危组、首发组及正常组人群进行认知功能评定,并运用阳性与阴性症状量表（PANSS）对各组的精神病性症状进行评估;评估认知功能与精神病症状的相关性。对首发组患者采用帕利哌酮进行治疗,观察治疗前后 CPT、Stroop 色词测验及 PANSS 评分。结果3组 CPT 和 Stroop 色词测验存在显著性差异（ P ﹤0.05）;PANSS 总分与 CPT 存在相关性。首发精神分裂症患者治疗后,CPT 和 Stroop 色词测验得分均明显升高,PANSS 评分显著下降,与治疗前相比,差异有统计学意义（ P ﹤0.05）。结论认知功能缺损可能对精神分裂症发病有一定的预测价值;而疾病的发作可能会进一步加重这一缺损;且精神病性症状愈严重,患者的认知功能下降愈明显。帕利哌酮对首发精神分裂症有良好的治疗作用,能显著改善患者的认知功能和精神病理症状。     

Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan

BackgroundLong-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics.MethodsPatients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency.ResultsThere were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94–9.11) and 9.93 (5.88–15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32–2.99) and 3.10 (1.14–6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide.DiscussionNo increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.     

帕利哌酮缓释片治疗儿童青少年精神分裂症临床研究

目的：探讨帕利哌酮缓释片治疗儿童青少年精神分裂症患者的疗效和安全性。方法对20例儿童青少年精神分裂症患者予以帕利哌酮缓释片治疗,观察8周。于治疗前后采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应。结果本组患者治疗后阳性与阴性症状量表总分及各因子分较治疗前显著下降（ P＜0.05或0.01）,治疗8周末显效率为45.0％,总有效率为70.0％;不良反应发生率低,程度较轻,主要表现为失眠、静坐不能、心动过速等。结论帕利哌酮缓释片治疗儿童青少年精神分裂症患者疗效显著,起效快,安全性高。     

Expected clinical benefits of paliperidone extended-release formulation when compared with risperidone immediate-release

Background: The development of paliperidone extended release (ER) may represent a new strategy to improve the pharmacological treatment of schizophrenia. The drug maintains the atypical antipsychotic profile of its parent compound risperidone, but it is associated with an innovative delivery system (OROS technology) that offers the possibility to obtain smooth drug plasma levels using an oral antipsychotic. Clinical trials confirmed that paliperidone ER is efficacious in the management of schizophrenia and well tolerated, however no direct clinical comparisons between paliperidone ER and immediate-release formulations of risperidone have been conducted to date. Objective: The present study evaluates possible differences between paliperidone ER and immediate-release formulations of risperidone due to structural/molecular and delivery system diversities, providing an estimation of their significance in the context of clinical results. Methods: A search of Medline and EMBASE was performed using the keywords ‘Risperidone’, ‘Paliperidone’ and ‘OROS technology’. Results/conclusion: The analysis suggests that the chemical structure and pharmacokinetic profile of paliperidone ER might provide clinical benefits in terms of efficacy, tolerability and more consistent drug response among patients, when compared with the parent compound risperidone in its immediate release formulations. The relevance of these differences is discussed, taking into account several clinical aspects involved in the drug therapy of schizophrenia.     

帕利哌酮缓释片对催乳素及糖脂代谢的影响

目的：探讨帕利哌酮缓释片治疗精神分裂症患者前后催乳素（PRL）及糖脂水平的变化。方法：47例精神分裂症患者接受帕利哌酮缓释片治疗8周。于治疗前和治疗4、8周抽取空腹血测定PRL、胰岛素（INS）、血糖（FBS）、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL）、低密度脂蛋白胆固醇（LDL）、载脂蛋白A1（ApoA1）、载脂蛋白B（ApoB）水平,同时测量患者腹围及体质量变化。结果：治疗4周和8周,男性患者PRL水平由治疗前（31.53±19.27）ng/ml分别升高至（42.24±18.45）ng/ml和（40.47±26.53）ng/ml（P〈0.01）;女性患者PRL水平由（78.13±48.70）ng/ml分别升高至（138.38±58.92）ng/ml和（135.12±56.47）ng/ml（P〈0.01）;以女性患者PRL水平较男性患者升高显著（P〈0.01）。PRL水平与帕利哌酮缓释片剂量相关性无统计学意义（P均〉0.05）。比较治疗前和治疗4、8周后FBS、INS、TG、TC、HDL、LDL、ApoA1、ApoB水平及患者腹围、体质量的变化,差异均无统计学意义（P均〉0.05）。结论：帕利哌酮缓释片可明显升高血清PRL水平,以女性患者升高显著,而对糖脂代谢的影响较小。