Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model

Background Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.     

Generalization testing with atypical and typical antipsychotic drugs in rats trained to discriminate 5.0 mg/kg clozapine from vehicle in a two‐choice drug discrimination task

Clozapine (CLZ) drug discrimination is used as a preclinical model to evaluate compounds for putative atypical antipsychotic properties. In rats, a 1.25 mg/kg CLZ training dose appears to have greater pharmacological specificity for atypical antipsychotic drugs than the traditional 5.0 mg/kg CLZ training dose; however, methodological differences among studies have precluded a direct comparison between these training doses. In the present study, rats were trained to discriminate a 5.0 mg/kg CLZ dose from vehicle in a two‐choice drug discrimination task using methods similar to those in a previous study from our laboratory that used a 1.25 mg/kg CLZ training dose. Clozapine produced full substitution (≥80% CLZ‐lever responding) for itself at the training dose (5.0 mg/kg). The atypical antipsychotics olanzapine, quetiapine, and ziprasidone also produced full substitution for 5.0 mg/kg CLZ, whereas the atypical antipsychotics risperidone and sertindole produced partial substitution (≥60% CLZ‐lever responding). The typical antipsychotic, thioridazine, produced full substitution for the 5.0 mg/kg CLZ training dose, but the typical antipsychotics chlorpromazine, fluphenazine, and haloperidol failed to substitute for clozapine. In a subgroup of 1.25 mg/kg CLZ‐trained rats, ziprasidone produced strong partial substitution (73.0 % CLZ‐lever responding) for the 1.25 mg/kg CLZ training dose. Based on these findings, some atypical antipsychotic drugs (i.e., quetiapine and ziprasidone) produce full substitution only for the 5.0 mg/kg CLZ training dose, whereas other atypical antipsychotic drugs (i.e., sertindole and risperidone) produce full substitution only for the 1.25 mg/kg CLZ training dose. Thus, both of these training doses are important for the screening of putative atypical antipsychotic drugs with the clozapine drug discrimination assay. Drug Dev. Res. 64:55–65, 2005. © 2005 Wiley‐Liss, Inc.     

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.     

齐拉西酮注射液治疗躁狂发作激越症状的研究

目的：以氟哌啶醇注射液为对照,评价齐拉西酮注射液治疗躁狂发作急性期激越患者的疗效及安全性。方法：符合ICD-10双相I型躁狂发作诊断标准的患者70例,随机分配到齐拉西酮注射液治疗组（试验组）和氟哌啶醇注射液治疗组（对照组）各35例,对患者进行基线评价,以及肌注治疗后的2、12、24、48和72h的评价。采用PANSS兴奋因子量表评价主要疗效,采用副反应症状量表（TESS量表）评定药物的不良反应。结果：两组72h时试验组总有效率为71．43％,对照组总有效率为68．57％。药物治疗72h后与基线比较,试验组PANSS兴奋因子得分减分平均为（11．32±4．15）分,对照组PANSS兴奋因子得分减分平均为（11．76±4．23）分。两组主要疗效指标差异无统计学意义（P〉0．05）。试验组锥体外系不良反应较对照组明显减少,TESS量表评分在治疗前后差异无统计学意义（P〉0．05）;对照组出现锥体外系不良反应较多,治疗前后差异有统计学意义（P〈0．05）。结论：甲磺酸齐拉西酮注射液可快速有效控制躁狂发作的激越症状,疗效与氟哌啶醇注射液相当,但安全性更高。     

齐拉西酮治疗急性期精神分裂症患者的疗效和安全性

目的探讨齐拉西酮治疗急性期精神分裂症住院患者的有效性和安全性。方法于治疗前、治疗1、2、4和8周后,以临床疗效总评量表（CGI）、个人与社会表现量表（PSP）及阳性和阴性症状量表（PANSS）评定急性期精神分裂症患者精神症状和社会功能;于治疗前和治疗8周后,以包含7个认知领域（词语流畅、抽象／执行功能、信息处理速度、工作记忆、学习、延迟回忆和运动功能）的神经心理成套测验评定患者认知功能。结果与治疗前相比,患者治疗8周后的CGI、PANSS、PSP评分具有统计学差异（P〈0．05）;与治疗前相比,患者治疗8周后神经认知评定中WAIS-Ⅲ符号搜索、RBANS即刻记忆、语言和总分具有统计学差异（P〈0．05）。结论齐拉西酮治疗急性期精神分裂症疗效好,且不良反应较轻。     

国产齐拉西酮与维思通治疗精神分裂症的对照研究

目的 探讨国产齐拉西酮治疗精神分裂症的疗效和安全性.方法 将71例精神分裂症住院患者随机分为齐拉西酮治疗组(5例)和维思通治疗组(36例),于治疗前和治疗第1、2、4、6w末采用阳性与阴性症状量表(PANSS)评定患者的疗效,以治疗中需处理的不良反应症状量表(TESS)评定患者的副反应.结果 71例患者均完成6周观察.在治疗第6周末,齐拉西酮组有效率88.6%,显效率60.0%;维思通组有效率86.1%,显效率61.1%,两组患者疗效(x2=0.180,P=0.981)方面的差异未达到统计学显著程度,但齐拉西酮对阴性症状的改善优于维思通.齐拉西酮组不良反应少、严重程度轻,很少引起锥体外系反应、体重增加.结论 齐拉西酮是一种安全有效的抗精神病药,尤其有助于阴性症状的改善.     

利培酮喹硫平齐拉西酮对首发精神分裂症患者代谢指标的影响

目的：探讨利培酮、喹硫平、齐拉西酮对首发精神分裂症患者代谢指标的影响。方法将120例首发精神分裂症患者按随机数字表法分为3组,分别口服利培酮、喹硫平、齐拉西酮治疗,观察12周。于治疗前后采用阳性与阴性症状量表评定临床疗效,同时检测血压、腰围及空腹血糖、三酰甘油、高密度脂蛋白胆固醇水平的变化,统计各时点代谢综合征发生率。结果治疗后利培酮组总有效率为89．2％、喹硫平组为88．9％、齐拉西酮组为86．5％,3组间比较差异无显著性（P＞0．05）。治疗4周末起利培酮组、喹硫平组腰围、三酰甘油、空腹血糖水平较治疗前显著升高,治疗12周末3组腰围、三酰甘油、空腹血糖水平均较治疗前显著升高（ P＜0．05或0．01）,利培酮组、喹硫平组高密度脂蛋白胆固醇水平较治疗前显著下降（P＜0．05）;治疗各时点利培酮组与喹硫平组腰围、三酰甘油水平及代谢综合征发生率均显著高于齐拉西酮组（ P＜0．05或0．01）。结论利培酮、喹硫平、齐拉西酮治疗首发精神分裂症疗效均显著,总体疗效相当,但对患者机体代谢均存在不同程度的影响,其中利培酮、喹硫平最为明显,齐拉西酮影响较小。     

齐拉西酮对男性精神分裂症临床疗效及生活质量的影响

目的：探讨齐拉西酮对男性精神分裂症患者临床疗效及生活质量的影响。方法将66例男性精神分裂症患者随机分为两组,每组33例,研究组口服齐拉西酮治疗,对照组口服利培酮治疗,观察10周。于治疗前后采用简明精神病评定量表评定临床疗效,副反应量表评定不良反应,生活质量综合评定问卷评定生活质量。结果治疗后两组简明精神病评定量表评分均较治疗前显著下降（P＜0．01）,两组间评分比较差异均无显著性（P＞0．05）。两组不良反应较轻微,研究组总体不良反应发生率以及锥体外系反应、体质量增加发生率显著低于对照组（P＜0．05）。治疗10周末研究组生活质量综合评定问卷总分及身体健康、心理健康维度分显著高于对照组（ P＜0．05或0．01）。结论齐拉西酮治疗男性精神分裂症疗效显著且与利培酮相当,不良反应发生率低、治疗依从性好,有利于提高患者的生活质量。     

Atypical antipsychotic drugs: Part II

This is the second of two columns on atypical antipsychotic drugs. Part II discusses olanzapine, quetiapine, and ziprasidone.