帕利哌酮缓释剂治疗首发与复发精神分裂症的临床疗效比较

目的比较帕利哌酮缓释剂治疗首发、复发精神分裂症患者的临床疗效。方法以28例首发精神分裂症患者（首发组）和32例复发再次住院的精神分裂症患者（复发组）为研究对象,分别给予帕利哌酮缓释剂治疗,于入院时、治疗2、4及8周末,采用阳性与阴性症状量表（PANSS）评定疗效。结果治疗前首发组与复发组PANSS总分、阳性症状量表分、阴性症状量表分及一般病理量表分差异均无统计学意义（P〉0.05）。治疗后第2、4和第8周末,首发组PANSS总分、阳性症状分量表分、阴性症状分量表分及一般病理量表分逐渐降低,差异有统计学意义（P〈0.05）;复发组PANSS总分、阳性症状分量表分及一般病理量表分逐渐降低,差异有统计学意义（P〈0.05）;而复发组阴性症状分量表分虽也逐渐降低,但至第4周后差异方有统计学意义。治疗8周末首发组显效率为46.43%,复发组显效率为43.75%,两组比较差异无统计学意义（χ2=0.043,P=0.835）。两组患者不良反应差异无统计学意义（P〉0.05）。结论帕利哌酮缓释剂治疗首发、复发精神分裂症患者阴阳性症状均具有良好的疗效,且安全性、依从性好,可在临床进一步推广应用。     

不同半衰期帕利哌酮治疗精神分裂症依从性、疗效和安全性的比较

目的 比较3种不同半衰期帕利哌酮治疗精神分裂症的依从性、疗效和安全性。方法 采用方便抽样法，选取2019年8月至2020年8月在河北医科大学第一医院精神科及邯郸市中心医院心理科住院或门诊治疗的187例精神分裂症患者为研究对象。按照患者和医生的意愿分为帕利哌酮缓释片组（Pali-ER,n=65）、棕榈酸帕利哌酮注射液组（PP1M,n=67）和棕榈帕利哌酮酯注射液组（PP3M,n=55），并进行为期12个月的治疗。分别于治疗前及治疗第3、6、9、12个月采用阳性与阴性症状量表（PANSS）比较不同时间点3组患者的临床症状，比较3组患者的持续治疗时间、不良反应发生情况。结果 研究过程中，Pali-ER组共有27例患者退出研究，其中21例停止治疗，4例更换药物，2例住院；PP1M组共17例患者退出，其中9例停止治疗，4例更换药物，4例住院；PP3M组共6例患者退出，其中5例停止治疗，1例更换药物。Pali-ER组的持续治疗时间为（9.169±0.506）个月（95%CI:8.178～10.161），短于PP1M组的（10.254±0.425）个月和PP3M组的（11.455±0.219）个月（...     

帕利哌酮缓释片对精神分裂症疗效及安全性的对照研究

目的 探讨帕利哌酮缓释片对精神分裂症的疗效及安全性.方法 选择精神分裂症患者分为研究组(31例,帕利哌酮缓释片治疗)和对照组(92例,利培酮治疗),共治疗4周,基线时、治疗后第2周末及治疗后第4周末应用阳性与阴性症状量表(PANSS)、住院病人观察量表(NOSIE)和副反应量表(TESS)分别评定疗效及安全性.结果 研究组在治疗后第2周末及第4周末的PANSS各因子分及总分均低于基线时,差异均具有显著性意义(P<0.05).在治疗后第2周末及第4周末,研究组的PANSS各因子分及总分均低于对照组,差异具有显著性意义(P<0.05).在治疗后第2周末及第4周末,研究组NOSIE评分的社会功能、社会兴趣、总积极因素因子分、激惹、精神病表现、抑郁、迟缓、总消极因素因子分以及病情总估分较对照组均有不同程度的改善,差异均具有显著性意义(P<0.05).研究组的不良反应与对照组相当,均未见严重不良反应.结论 帕利哌酮缓释片可有效改善精神分裂症患者的阳性症状、阴性症状以及社会功能.安全性较高.     

帕利哌酮和奥氮平对精神分裂症患者阳性症状、血脂、体质量的影响

目的对比帕利哌酮与奥氮平对精神分裂症患者阳性症状、血脂、体质量的影响。方法将70例精神分裂症患者随机分为帕利哌酮组和奥氮平组各35例。分别使用帕利哌酮缓释剂和奥氮平治疗,疗程均为8周。2组均采用阳性与阴性症状量表(PANSS)评定疗效,同时对比血脂、体质量的影响,评定不良反应。结果 2组疗效均显著,组间比较差异无统计学意义(P>0.05);帕利哌酮缓释剂组在导致体质量增加的不良反应明显低于奥氮平组(P<0.05),在对血脂的影响方面2组比较无统计学意义(P>0.05)。结论帕利哌酮可作为精神分裂症的一线用药和维持治疗用药,疗效可靠,导致体质量增加的不良反应少于奥氮平。     

帕利哌酮缓释片治疗非急性期精神分裂症疗效及安全性的开放性研究

目的 评价可变剂量帕利哌酮缓释片治疗既往口服抗精神病药缺乏疗效或无法耐受而需换药的非急性期精神分裂症患者的疗效及安全性.方法 本研究为非随机、单组、为期12周的多中心的开放性临床研究,共纳入405例患者.主要疗效指标为治疗第12周末阳性和阴性症状量表( PANSS)评分较基线的变化.次要疗效指标包括:临床总体印象-严重度量表(CGI-S)、个人和社会功能量表(PSP).安全性评价包括不良反应记录、锥体外系症状评定量表(ESRS)、实验室及生命体征监测等.结果 PANSS总分由基线的(70.1±19.3)分下降至治疗终点的(48.1±15.7)分(P＜0.01),CGI-S由基线的(4.1±1.2)分下降至治疗终点的(2.5±1.1)分(P＜0.01),PSP总分由基线的(58.6±14.9)分提高至治疗终点的(74.5±13.4)分(P＜0.01).发生率＞5％的不良反应有:锥体外系反应(39.0％)、失眠(6.5％)和过度镇静(5.5％),ESRS总分由基线的(13.0±2.1)分下降至治疗终点的(12.6±1.6)分(P＜0.01).平均体质量治疗终点较基线增加(0.2±3.5)kg (P ＜0.05).结论 换用可变剂量帕利哌酮缓释片对既往抗精神病药疗效不佳或耐受性不佳的非急性期精神分裂症患者疗效肯定,并具有较好安全性和耐受性.     

帕利哌酮与阿立哌唑治疗精神分裂症的临床疗效

目的探讨帕利哌酮缓释片与阿立哌唑常释片治疗精神分裂症的临床疗效。方法选取于我院就诊的精神分裂症患者171例,随机分为对照组和实验组,对照组采用阿立哌唑治疗,实验组采用帕利哌酮进行治疗,比较2组PANSS评分、TESS评分和有效率。结果 2组治疗后2周、4周、6周、8周以及12周的PANSS和TESS评分差异具有统计学意义(P0.05)。2组临床疗效差异有统计学意义(P0.05)。结论帕利哌酮是安全有效的抗精神类药物,起效快,不良反应少,值得临床推广。     

棕榈酸帕利哌酮对女性精神分裂症疗效与安全性的研究

目的探讨棕榈酸帕利哌酮对女性精神分裂症的疗效与安全性。方法对112例患者根据性别分为研究组(女性)和对照组(男性),用棕榈酸帕利哌酮注射,首次剂量150mg,间隔8天100mg,之后每月1次,可变剂量75 mg^150 mg。采用阳性与阴性症状量表(PANSS)、临床总体印象量表疾病严重程度分量表(CGI-S)评定患者精神症状与疗效的变化;副作用量表(TESS)、实验室、血生化变化评价安全性。在治疗前与治疗1周、4周、8周、16周末评定。结果两组患者PANSS、CGI-S评分在治疗1、4、8、16周末均降低,与治疗前比较,差异均有显著性(P<0.05);34例出现EPS与胆碱能反应,10例月经紊乱。结论棕榈酸帕利酮注射后1周即起效,4~8周达到可靠疗效,易发生EPS与胆碱能反应,导致女性月经紊乱,不影响继续使用,可获得满意的临床疗效,为长期治疗提供了新选择。     

帕利哌酮缓释片治疗急性精神分裂症的疗效及安全性分析

目的探讨帕利哌酮缓释片治疗急性精神分裂症的临床疗效及安全性。方法选取我院2015-07-2016-05诊治的急性精神分裂症患者74例为研究对象,并遵照随机抽签方式分组,治疗组(n=37)应用帕利哌酮缓释片,对照组(n=37)口服利培酮片,对比2组临床疗效及不良反应发生率。结果 (1)治疗组治疗总有效率为97.3%,高于对照组的78.4%(P0.05);(2)治疗组不良反应事件发生率为10.8%,低于对照组的46.0%(P0.01);(3)治疗组治疗后PANSS总分是(44.1±3.5)分,低于对照组的(67.7±5.6)分(P0.01)。结论帕利哌酮缓释片治疗急性精神分裂症的临床疗效显著,安全性较高,可作为急性精神分裂症患者首选治疗药物。     

氯氮平联合帕利哌酮治疗难治性精神分裂症疗效及不良反应研究

目的 探讨氯氮平联合帕利哌酮治疗难治性精神分裂症的临床疗效及安全性。方法 应用阳性和阴性综合征量表（PANSS）及治疗中需处理的不良反应症状量表（TESS）对单用氯氮平治疗的难治性精神分裂症患者（82例）分别于治疗前后进行评分,将单用氯氮平治疗无效的32例患者改用氯氮平联合帕利哌酮治疗,并用PANSS及TESS量表评定联合治疗前后的疗效及不良反应。结果 联合治疗患者在治疗后第8、12周末PANSS总分及各因子分均较治疗前下降（P〈0.05）,治疗后第12周末有效率为48.62%。单用氯氮平治疗不良反应发生率（62.5%）高于联合治疗（37.5%）（P〈0.05）,流涎、心动过速、体质量增加不良反应发生率高于联合治疗（P〈0.01）,而泌乳素升高的不良反应发生率低于联合治疗（P〈0.05）。结论 氯氮平联合帕利哌酮治疗难治性精神分裂症疗效显著,不良反应较轻,但应用中注意泌乳素水平。     

帕利哌酮缓释片治疗急性精神分裂症疗效及安全性的对照研究

Objective The study was designed to evaluate the efficacy and safety of flexible doses of paliperidone extended-release tablets (paliperidone ER) (3 -12) mg/d comparing with olanzapine (5 -15)mg/d in acute hospitalized patients with schizophrenia. Methods All 288 hospitalized patients with DSM-Ⅳ schizophrenia were randomized into paliperidone ER ( n = 143 ) or olanzapine ( n=145 ) treatment in a 6-week, multicenter, double-blind, parallel-group study. The primary efficacy measure was the total score changes of the Positive and Negative Syndrome Scale (PANSS). Clinical Global Impression (CGI),response rate and Visual Analogue Scale (VAS) were adopted as secondary efficacy measures. Results Both paliperidone ER and olanzapine groups demonstrated a significant improvement in total PANSS score (P<0.001). The PANSS total score in paliperidone ER group was reduced (32.3 ± 17.1) at end point,and olanzapine group (34.1 ± 17.4). There was no statistically significant difference between the two groups (P =0.369) after 6-week treatment. There were no statistical differences between two groups in CGI,response rate and VAS sleep quality assessments by the end of the treatment. The common adverse events were extrapyramidal symptoms, insomnia, constipation and prolactin increasing in paliperidone ER group,and somnolenee, EPS, abnormal liver function and abnormal lipid metabolism in olanzapine group.Conclusion Paliperidone ER and olanzapine are similarly effective in significantly improving the symptoms of inpatient with acute schizophrenia. Paliperidone ER demonstrates a favorable safety profile with fewer somnolence, abnormal liver function and abnormal lipid metabolism comparing with olanzapine.     

喹硫平单药治疗精神分裂症急性发作的疗效和安全性研究

目的评价喹硫平600～750mg/d单药治疗精神分裂症急性发作的疗效和安全性。方法采用多中心、前瞻性、单组、开放性研究。对124例精神分裂症急性发作的住院患者予喹硫平600～750mg/d单药治疗,观察时间为24周。疗效指标为阳性与阴性综合征量表（PANSS）评分变化,蒙哥马利抑郁量表（MADRS）、Pittsburgh睡眠质量指数（PSQI）及大体评定量表（GAS）的评分。安全性指标包括不良事件的评估、实验室检查和生命体征等。结果终点时PANSS总分减分值为54.47,与基线相比差异有统计学意义（P〈0.01）。研究终点时,患者的有效率为77.4%（96/124）,缓解率为58.1%（72/124）。MADRS、PSQI和GAS各时点评分改变与基线的差异均有统计学意义（P均小于0.01）。PANSS总分、阳性、阴性及兴奋因子分自第1周起即明显下降,减分值分别为10.33、3.52、2.11及3.33（P均小于0.01）;此后访视点各评分继续减少。最常见的不良事件为便秘（23.3%）、一过性肝功能异常（14.7%）、心动过速（12.4%）、嗜睡（10.9%）和失眠（10.1%）,无药物相关的严重不良事件发生。结论喹硫平600～750mg/d单药治疗急性精神分裂症安全有效,可改善激越、阳性症状、阴性症状、抑郁症状、睡眠和总体功能。     

Safety and tolerability of deltoid and gluteal injections of paliperidone palmitate in schizophrenia

Paliperidone palmitate is an investigational, injectable atypical antipsychotic. The safety and tolerability of initiating treatment with paliperidone palmitate via deltoid versus gluteal injections given once monthly, and of switching injection sites, in adults with stable schizophrenia were assessed. In this crossover trial, stable outpatients (N = 252) were randomly assigned 1:1:1 to 3 dose groups (paliperidone palmitate 50, 75, or 100 mg eq.) and 2 treatment sequences (blinded to dose): deltoid muscle (period 1 [13 weeks]) followed by gluteal muscle (period 2 [12 weeks]) or the reverse. The intent-to-treat analysis set had 249 patients: mean age = 43 (SD: 12.8) years; 57% men, 81% white, baseline mean Positive and Negative Syndrome Scale (PANSS) total score = 56 (SD: 11.5). A total of 170 (68%) patients completed the study, with a similar proportion completing each treatment sequence. The incidence of systemic treatment-emergent adverse events (TEAEs) was similar between the 2 injection sites across doses during period 1 (deltoid [D]: 61% to 67%; gluteus [G]: 58% to 65%), and during the last 8 weeks of the 2 study periods (DG: 32% to 45% [period 1], 29% to 42% [period 2]; GD: 31% to 40% [period 1], 30% to 41% [period 2]). During the first treatment week, median plasma paliperidone concentrations were higher with treatment initiation in the deltoid muscle compared with the gluteal muscle. At apparent steady state, there was little difference in plasma paliperidone concentrations between the deltoid and gluteus sites for a given dose. Local tolerability was slightly better with gluteal injections. Patient preference for injection sites differed between geographical regions, e.g. patients from the US preferred deltoid to gluteal sites. The most common (≥ 5% overall) TEAEs were: (period 1) insomnia, anxiety, headache, and agitation; and (period 2) insomnia, psychotic disorder, weight increased, and tachycardia. Paliperidone palmitate treatment was tolerated, irrespective of injection site, and thus could offer the choice of administration into either the deltoid or gluteal muscle to meet patient and physician preference.     

Effects of paliperidone extended release on functioning level and symptoms of patients with recent onset schizophrenia: An open-label,single-arm,flexible-dose, 12-months follow-up study

Abstract

Background: Response to antipsychotic treatment is better in the early stages of schizophrenia. Aims: The primary objective of this non-randomized, single-arm, multicenter clinical trial was to explore the response to treatment and safety of a flexible dose of paliperidone (mean = 6.42 mg/day) in patients with recent onset schizophrenia (< 3 years after the first episode/hospitalization). Methods: Severity of clinical symptoms was evaluated by the Positive and Negative Syndrome Scale (PANSS), functioning was assessed using the Global Assessment of Functioning (GAF) scale and the Personal and Social Performance Scale (PSP). Results: In a total of 85 patients enrolled, 80 patients were eligible. Total PSP score at baseline (50.2 ± 11.6) increased at all visits. Total PSP score was 65.4 ± 12.1 at month 12 (P < 0.001). GAF scores were significantly higher at all visits compared with baseline (P = 0.001). It was 62.4 ± 12.5 with an increase of 42.9% at month 12 (P < 0.001). PANSS Positive and Negative subscales and General psychopathology subscale scores showed significant reductions beginning with month 3 and were 11.9 ± 3.8 (29.3%; P < 0.001), 13.7 ± 5.6 (27.3% P < 0.001) and 27.8 ± 7.1 (23.2%; P < 0.001) at month 12, respectively. Twelve patients (14.3%) had a serious adverse event. The most common adverse events were insomnia (17.9%), nausea (8.3%), akathisia (4.8%), anxiety (4.8%) and depression (4.8%). Body weight values at the end of the study were significantly higher compared with baseline. Conclusion: The present study demonstrates that flexible dose of paliperidone resulted in a significant improvement in functioning and reduction in symptoms in patients with recent onset schizophrenia.     

帕利哌酮与氟哌啶醇治疗精神分裂症患者的随机对照研究

目的:探讨帕利哌酮缓释片对急性期精神分裂症患者精神病性症状、认知功能、生活质量及社会功能改善作用。方法:以开放、随机的方法将60例门诊急性期精神分裂症患者分为两组,分别给予帕利哌酮和氟哌啶醇治疗,疗程16周。分别于治疗前及治疗8、12、16周采用阳性与阴性症状量表(PANSS)评估精神症状,采用威斯康星卡片分类测验(WCST)、持续性操作测验(CPT)、成人韦氏智力量表(WAIS)中的数字广度测验评估认知功能,采用生活质量和满意度自评问卷(Q-LES-Q)评估生活质量,采用个人和社会功能量表(PSP)评估社会功能;并进行组间比较。结果:治疗后两组各时点PANSS评分明显低于治疗前(P均0.01),两组间比较差异无统计学意义。治疗后帕利哌酮组WCST、CPT成绩明显好于治疗前及氟哌啶醇组(P0.05或P0.01);Q-LES-Q评分较治疗前明显提高(F=8.71,P0.01),且治疗第12及16周时明显高于氟哌啶醇组(t=2.58,2.84;P均0.01)。治疗后两组PSP评分明显高于治疗前,且帕利哌酮组明显高于氟哌啶醇组(P0.05或P0.01)。结论:帕利哌酮和氟哌啶醇对精神分裂症急性期精神症状的改善作用相当,但帕利哌酮对患者的认知功能、生活质量及社会功能也有较好的改善作用。     

Effects of acute paliperidone palmitate treatment in subjects with schizophrenia recently treated with oral risperidone

Objective

To examine efficacy and safety of acute treatment with paliperidone palmitate in subjects with schizophrenia whose disease remained symptomatic despite recent treatment with oral risperidone.

Methods

Post hoc analysis of a 13-week, double-blind, placebo-controlled study of subjects with symptomatic schizophrenia randomized to paliperidone palmitate 39, 156, or 234 mg (25, 100, or 150 mg equivalents of paliperidone) or placebo. Paliperidone palmitate subjects received a 234-mg day 1 dose, followed by their assigned dose on day 8 and monthly thereafter. Subjects treated with oral risperidone within 2 weeks before randomization regardless of duration were included. Assessments: PANSS, CGI-S, PSP scores; AEs. ANCOVA models with LOCF methodology evaluated treatment group differences.

Results

216 subjects received prior oral risperidone (paliperidone palmitate 39 mg, n = 53; 156 mg, n = 58; 234 mg, n = 48; placebo, n = 57). Median prior risperidone use was 22 days. Significant improvement was observed with paliperidone palmitate 156-mg or 234-mg versus placebo in least-squares mean (SE) score change at end point in PANSS total (156 mg, −15.8 [3.0], p = 0.0001; 234 mg, −17.6 [3.2], p = 0.0001), CGI-S (156 mg, −0.9 [0.2], p = 0.0068; 234 mg, −1.1 [0.2], p = 0.0003), and PSP (156 mg, 10.7 [2.3], p = 0.0061; 234 mg, 12.9 [2.4], p = 0.0009). Most common AEs (≥ 10%) in any paliperidone palmitate group were insomnia, anxiety, and headache.

Conclusions

In subjects with schizophrenia who recently received oral risperidone but who remained symptomatic, acute treatment with monthly doses of 156-mg and 234-mg paliperidone palmitate significantly improved clinical symptoms, global illness ratings, and functioning compared with placebo, with no unexpected safety findings.     

利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射治疗精神分裂症急性激越症状疗效和安全性的研究

目的 比较利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射(以下简称肌注)对精神分裂症急性激越症状的疗效和安全性,以及由氟哌啶醇肌注换利培酮口服(以下简称换药组)对急性期疗效的影响.方法 205例伴有急性激越症状的精神分裂症患者按随机数字表方法分为利培酮口服液组(104例)和氟哌啶醇肌注组(101例).研究分为急性激越症状疗效评价(治疗前5 d)和换药后急性期疗效评估(治疗6周)2个阶段.以阳性和阴性症状量表兴奋因子(PANSS-EC)及阳性和阴性症状量表(PANSS)总分作为主要疗效评价指标.安全性评估采用锥体外系副反应量表(Simpson-Angus Rating Scale,SAS)和静坐不能评定量表(Barnes Akathisia Scale,BAS)评定锥体外系症状、记录不良事件和实验室检查.结果 治疗前5 d利培酮口服液组和氟哌啶醇肌注组的急性激越症状都有明显改善(P＜0.01),2组间疗效差异无统计学意义(P＞0.05);利培酮口服液组合作程度好于氟哌啶醇肌注组(P＜0.05),锥体外系不良反应低于氟哌啶醇肌注组(P＜0.05).由氟哌啶醇肌注换利培酮口服后,治疗6周末口服组和换药组疗效及总体不良事件发生率比较差异均无统计学意义(P均＞0.05),但锥体外系不良反应换药组高于口服组,差异有统计学意义(P＜0.05).结论 利培酮口服液合用氯硝西泮口服治疗精神分裂症急性激越症状与氟哌啶醇肌注疗效相当,但利培酮口服液合作程度好,锥体外系不良反应发生率低.由氟哌啶醇肌注换利培酮口服对急性期疗效无明显影响.     

Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics

OBJECTIVE The Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study assessed the efficacy and tolerability of quetiapine (Seroquel?) in patients with schizophrenia switched from treatments providing suboptimal outcomes. METHODS This was an international, open-label, non-comparative study, designed with titration to 400 mg/day quetiapine over 7 days, then flexible dosing (300-750 mg/day) for 11 weeks. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS); Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores; and the Calgary Depression Scale for Schizophrenia (CDSS). Clinical benefit and tolerability were also assessed. RESULTS The mean modal dose of quetiapine was 505 mg/day; 509 patients switched to quetiapine from olanzapine (13%), risperidone (11%), conventional antipsychotics (37%) and combinations of antipsychotics (28%), amongst others. Significant decreases in CGI Severity of Illness and PANSS scores and a significant improvement in CDSS score resulted from the switch (all P&lt;0.001 versus baseline). There were significant reductions in extrapyramidal symptoms (EPS) on the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS) (both P&lt;0.001 versus baseline) and a low incidence of EPS-related adverse events (4.7%). CONCLUSION Results indicate that switching to quetiapine was clinically beneficial for patients with poor efficacy or intolerable side effects on their previous antipsychotic medication.     

Efficacy,safety, and tolerability of the low glycemic index treatment in pediatric epilepsy

Purpose: To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy. Methods: A retrospective chart review was performed on patients initiating the LGIT at the Massachusetts General Hospital between January 2002 and June 2008. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistries, side effects, and anthropometrics were collected. Initiation of the LGIT was done in an outpatient setting. Patients were educated by a dietitian to restrict foods with high glycemic index and to limit total daily carbohydrates to 40–60 g. Change in seizure frequency was assessed at 1‐, 3‐, 6‐, 9‐, and 12‐month follow‐up intervals. Results: Seventy‐six children were included in the study. Eighty‐nine percent had intractable epilepsy (≥3 antiepileptic drugs). A greater than 50% reduction from baseline seizure frequency was observed in 42%, 50%, 54%, 64%, and 66% of the population with follow‐up available at 1, 3, 6, 9, and 12 months, respectively. Increased efficacy was correlated with lower serum glucose levels at some time points, but not with β‐hydroxybutyrate (BOHB) changes or ketosis status at any time point. Only three patients reported side effects (transient lethargy). Blood urea nitrogen (BUN) was elevated in approximately one‐third of follow‐up laboratory studies. No significant changes were seen in body mass index (BMI) or BMI z‐score at any follow‐up interval. The most cited reason for treatment discontinuation was the restrictiveness of the diet, in 18 patients (24%). Conclusion: The LGIT was associated with reduced seizure frequency in a large fraction of patients, with limited side effects.     

Systematic review of the efficacy and tolerability of Clozapine in the treatment of youth with early onset schizophrenia

BackgroundThe use of clozapine (CLZ) for treatment-resistant schizophrenia is well established in adults. However, it is seldom used in youth with early onset schizophrenia (EOS) largely because of lack of clarity about its risk benefit ratio. This review synthesises and evaluates available evidence regarding the efficacy and tolerability of CLZ in EOS with the aim to assist clinical decision-making.MethodsWe conducted a systematic review of the primary literature on the clinical efficacy and adverse drug reactions (ADRs) observed during CLZ treatment in EOS. We also identified relevant practice guidelines and summarised current guidance.ResultsCLZ showed superior efficacy than other antipsychotics in treating refractory EOS patients; short-term clinical trials suggest an average improvement of 69% on the Brief Psychiatric Rating Scale that was sustained during long-term follow-up (up to 9 years). No fatalities linked to CLZ treatment were reported. Sedation and hypersalivation were the most common complaints, reported by over 90% of patients. Other common ADRs (reported in 10-60% of patients) were enuresis, constipation, weight gain, and non-specific EEG changes. Less common ADRs (reported in 10-30% of patients) were akathisia, tachycardia and changes in blood pressure. Neutropenia was reported in 6–15% of cases but was usually transient while agranulocytosis was rare (< 0.1%). Seizures were also uncommon (< 3%). Metabolic changes were relatively common (8–22%) but emergent diabetes was not frequently observed (< 6%). Overall the rate of discontinuation was low (3–6%). Current guidelines recommend the use of CLZ in EOS patients who have failed to respond to two adequate trials with different antipsychotics and provide detailed schedules of assessments to evaluate and assess potential ADRs both prior to initiation and throughout CLZ treatment.ConclusionAvailable data although limited in terms of number of studies are consistent in demonstrating that CLZ is effective and generally safe in the treatment of refractory EOS provided patients are regularly monitored     

A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia

This double-blind, multicenter study aimed to investigate the efficacy and safety of aripiprazole 10, 15 or 20 mg/day versus placebo. Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were randomized to once-daily aripiprazole 10, 15 or 20 mg/day or placebo for 6 weeks. The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total score (last observation carried forward). Patients with no improvement by Week 3 (Clinical Global Impression-Global Improvement score > or =4) could transfer to open-label aripiprazole 20mg/day. In total, 420 patients were randomized to placebo (n = 108); aripiprazole 10 mg/day (n = 106); 15 mg/day (n = 106); or 20 mg/day (n = 100). Of these, 142 patients (34%) completed 6 weeks of treatment, 131 (31%) discontinued to receive open-label aripiprazole, and 147 (35%) for other reasons. Aripiprazole 10, 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures, including PANSS Total, Positive and Negative scores, and the CGI-Severity of Illness score. Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day. All three doses were well tolerated. Overall, aripiprazole was not associated with clinically meaningful differences in extrapyramidal symptoms, prolactin or weight changes versus placebo. Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia.