Risperidone and cognitive function in children with disruptive behavior disorders.

BACKGROUND: Effects of risperidone on cognitive function in children with disruptive behavior disorders (DBDs) and subaverage intelligence quotient (IQ) were assessed. METHODS: Data from two 6-week, double-blind, placebo-controlled studies (n = 228) were combined, as were three 1-year, open-label studies (n = 688). Patients with DBDs and subaverage IQ, 5 to14 years, received placebo or risperidone .02 to .06 mg/kg/day. Cognitive measures included the Continuous Performance Task (CPT) and Verbal Learning Test for Children (VLT-C). Efficacy was assessed using the Nisonger Child Behavior Rating Form (NCBRF). Adverse events were collected via spontaneous report; sedation was assessed using visual analog scale. RESULTS: Improvements on the NCBRF Conduct Problem subscale were significantly greater for risperidone- versus placebo-treated patients (-15.8 vs. -6.4, p < .0001) in short-term studies; significant reductions were observed in long-term studies (-16.3, p < .0001). No overall decline and some significant improvement in attention (CPT) and memory (VLT-C) were noted regardless of treatment in short-term studies. VLT-C improved significantly (p < .0001) for both groups, with no difference between treatment groups. Improvements in memory (VLT-C) and attention (CPT) were noted in long-term studies. Somnolence/sedation did not affect cognitive function. CONCLUSIONS: Cognitive function was not altered by risperidone in short-term studies and was maintained or improved with one year of treatment in children with DBDs and subaverage IQ, potentially representing age-appropriate gains.     

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.     

Risperidone exerts potent anti-aggressive effects in a developmentally immature animal model of escalated aggression.

BACKGROUND: Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27-57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. METHODS: Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05-1.0 mg/kg, intraperitoneally). RESULTS: Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1-.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3-1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. CONCLUSIONS: These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression.     

利培酮治疗首发精神分裂症

为观察利培酮治疗首发精神分裂症的有效性及安全性 ,采用口服利培酮治疗 2 0例首发精神分裂症住院患者 ,疗程 8周 ,以PANSS评定疗效 ,TESS观察副反应。结果 :显效率 40 % ,有效率 75 % ,起效时间为 1周。说明利培酮能有效地治疗首发精神分裂症 ,对阳性、阴性症状都有效 ,副反应小 ,安全性高。     

利培酮与氯氮平治疗首发精神分裂症的对照研究

目的：比较利培酮和氯氮平治疗首发精神分裂症的有效性和安全性。方法：６０例ＢＰＲＳ总分≥４０分,符合ＣＣＭＤ－２－Ｒ精神分裂症诊断标准的患者,随机分为两组进行对照研究,分别给予利培酮和氯氮平口服治疗,以ＢＰＲＳ减分率为疗效评定指标,以ＴＥＳＳ评价副反应指标。结果：利培酮治疗首发精神分裂症疗效肯定,８周末有效率为９０％,与氯氮平相仿。利培酮在治疗１周后起效,焦虑、抑郁和迟滞等症状群起效更早,明显早于氯氮平。剂量较小者锥体外系副反应轻,其它不良副反应发生率和严重程度均较氯氮平少而轻。结论：利培酮是治疗精神分裂症有效、安全的一线抗精神病药物     

精神分裂症患儿利司培酮治疗前后血清瘦素和白细胞介素-1β变化的意义

目的探讨精神分裂症患儿利司培酮治疗前后血清瘦素和白细胞介素-1β(IL-1β)水平的变化及意义。方法观察组31例精神分裂症患儿,利司培酮治疗前和治疗8周后分别测量身高、体质量以计算体质量指数(BMI),用放射免疫法检测其空腹血清瘦素和IL-1β。选取31例健康儿童作为对照组。结果观察组治疗后BMI、血清瘦素水平均明显上升,与治疗前相比差异均有显著性(P均<0.05);观察组血清IL-1β水平在治疗前与对照组相比明显增高,治疗后明显下降,与治疗前相比差异有显著性(P<0.05)。结论首发精神分裂症患儿血清IL-1β水平明显升高,利司培酮治疗后易出现药源性肥胖,低IL-1β水平可能是瘦素抵抗的原因之一。     

阿立哌唑治疗精神分裂症的多中心随机双盲对照试验

目的:评价阿立哌唑治疗精神分裂症的疗效及安全性。方法:采用多中心随机双盲双模拟、阳性药平行对照的方法。以利司哌酮(昔名利培酮)为对照,受试者分别口服阿立哌唑10~30 mg.d-1与利司哌酮2~6 mg.d-1,疗程42 d。结果:共收集精神分裂症病人222例,其中阿立哌唑组111例与利司哌酮组111例。治疗结束时,2组PANSS总分与BPRS总分较治疗前均显著降低(P<0.01);PANSS总分减分率阿立哌唑组(65±s28)%,利司哌酮组为(67±26)%,差异无显著意义(P>0.05)。临床总有效率:阿立哌唑组为77.0%,利司哌酮组为79.2%,2组比较差异无显著意义(P>0.05)。阿立哌唑组常见的不良反应为:静坐不能、震颤、失眠、心动过速,不良反应较利司哌酮组少。结论:阿立哌唑治疗精神分裂症的疗效与利司哌酮相似,不良反应较利司哌酮为少,是一种安全而有效的抗精神病药。     

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.     

利培酮与氯氮平治疗精神分裂症各30例的比较

比较利培酮与氯氮平治疗精神分裂症的疗效和不良反应。方法 :男性精神分裂症 6 0例 ,分为利培酮组 30例 [年龄 (2 8±s 6 )a ,病程 (5 .7± 1.6 )a],氯氮平组 30例 [年龄 (2 8± 7)a ,病程 (5 .1± 1.6 )a],利培酮组给利培酮 ,开始 1～ 2mg·d- 1,2wk内加至 6～ 8mg·d- 1,氯氮平组给氯氮平 ,开始 5 0～10 0mg·d- 1,2wk内加至 30 0～ 4 0 0mg·d- 1,8wk为一个疗程。采用简明精神病量表 (BPRS)和副反应量表 (TESS)评定疗效和不良反应。结果 :利培酮与氯氮平组治疗精神分裂症总有效率均为 90 %(P >0 .0 5 ) ,2组治疗前、后BPRS评分差异有非常显著意义 (P <0 .0 1) ,2组治疗后TESS评分差异有显著意义 (P <0 .0 5 )。结论 :利培酮组与氯氮平组治疗精神分裂症疗效相当 ,但利培酮不良反应少。