BACKGROUND & AIMS: OBJECTIVES:To evaluate the effectiveness and safety of risperidone in children and adolescents with bipolar disorder characterized by aggression and mania, despite treatment with mood stabilizers. METHODS:A retrospective chart review of patients seen in an outpatient pediatric mood disorders clinic over an 18-month period was performed. Data were extracted from charts of patients who had a diagnosis of bipolar disorder with aggression that was uncontrolled on a mood stabilizer; as a result, these patients had risperidone added to their regimen. RESULTS:Four boys (aged 7-15 years) and two girls (aged 8 and 14 years) were treated with risperidone (mean dosage, 0.85 mg/day) for 3-16 months. Aggressive behavior improved in all patients after risperidone was started and remained improved for the duration of follow-up. Other symptoms of mania also improved. Risperidone was generally well tolerated. Sedation and akathisia were reported in one patient. CONCLUSIONS:The addition of risperidone to a mood stabilizer may improve aggression and other symptoms of mania in pediatric patients with bipolar disorder who do not respond adequately to a mood stabilizer alone. The long-term efficacy and safety of this regimen should be evaluated in a controlled clinical trial.

背景与目标： 目的：评估利培酮在以情绪低落为特征的双相情感障碍儿童和青少年中的有效性和安全性，尽管使用了情绪稳定剂进行了治疗。
方法：对在门诊儿科情绪障碍诊所接受治疗的18个月内的患者进行回顾性图表审查。数据是从诊断为躁郁症的躁郁症患者的图表中提取的，这些患者的情绪稳定剂无法控制；结果，这些患者的方案中增加了利培酮。
结果：四个男孩（7-15岁）和两个女孩（8和14岁）接受利培酮（平均剂量0.85 mg /天）治疗3-16个月。开始使用利培酮后所有患者的攻击行为均得到改善，并在随访期间保持改善。躁狂症的其他症状也有所改善。利培酮通常耐受良好。据报道一名患者出现镇静和静坐不全。
结论：在情绪稳定剂中加入利培酮可能会改善躁郁症儿科患者的攻击性和躁狂症的其他症状，这些患者不能单独对情绪稳定剂产生足够的反应。该方案的长期疗效和安全性应在对照临床试验中进行评估。

BACKGROUND & AIMS: :Data from the EMBLEM Study, a 2-year, prospective, observational study of health outcomes associated with acute treatment of patients experiencing a manic/mixed episode of bipolar disorder, was used to compare the effectiveness of olanzapine monotherapy versus risperidone monotherapy, and to investigate whether the treatment effects were similar to those reported in a 3-week, randomized controlled trial assessing the same treatments. Symptom severity measures included the Young Mania Rating Scale (YMRS), the 5-item Hamilton Depression Rating Scale, and the Clinical Global Impression-Bipolar Disorder Scale. A total of 245 EMBLEM inpatients were analyzed with YMRS >or=20: olanzapine (n=209), risperidone (n=36). Both the treatment groups had similar improvements in YMRS from baseline to 6 weeks, but there was a significantly greater improvement in 5-item Hamilton Depression Rating Scale in the olanzapine group. There was a similar improvement in Clinical Global Impression-Bipolar Disorder Scale in both the groups and the occurrence of treatment-emergent adverse events and weight gain did not differ between the treatment groups. The EMBLEM results partly support those of the randomized controlled trial, which suggests olanzapine and risperidone have similar improvements in mania but that olanzapine monotherapy may be more effective than risperidone monotherapy in the treatment of depressive symptoms associated with mania. Limitations include differences in study design, patient population, and length of follow-up.

背景与目标： ：来自EMBLEM研究的数据是一项为期2年的前瞻性，观察性研究，涉及与躁狂/躁狂混合发作的躁郁症患者急性治疗相关的健康结局，用于比较奥氮平单药治疗与利培酮单药治疗的有效性，并且调查治疗效果是否与评估相同治疗的3周随机对照试验中报道的效果相似。症状严重程度包括年轻躁狂量表（YMRS），5项汉密尔顿抑郁量表和临床总体印象-双相情感障碍量表。共有245名EMBLEM住院患者接受YMRS≥20的分析：奥氮平（n = 209），利培酮（n = 36）。从基线到第6周，两个治疗组的YMRS均有相似的改善，但奥氮平组的5项汉密尔顿抑郁量表的改善显着更大。两组的临床总体印象-双相情感障碍量表都有相似的改善，并且在治疗组之间出现治疗紧急不良事件和体重增加的情况没有差异。 EMBLEM结果部分支持随机对照试验的结果，该结果表明奥氮平和利培酮在躁狂症方面有相似的改善，但奥氮平单一疗法在治疗与躁郁症相关的抑郁症状方面可能比利培酮单一疗法更有效。局限性包括研究设计，患者人群和随访时间的差异。

BACKGROUND & AIMS: PURPOSE:Intraoperative floppy iris syndrome (IFIS) has been strongly associated with intake of selective a1 adrenergic blockers, particularly tamsulosin. Intraoperative floppy iris syndrome has also been linked to the use of other drugs with some a antagonist activity. METHODS:We identified patients on long-term treatment with the antipsychotic agent risperidone who showed typical features of IFIS during cataract surgery. RESULTS:We report 3 eyes in 2 patients taking risperidone in which typical features of IFIS were noted during cataract surgery. CONCLUSIONS:Risperidone is a widely prescribed drug in psychiatric practice and has a-blocking actions as well as strong affinity for serotonin 2A receptors. Ophthalmologists should be aware of the possible association with IFIS when performing cataract surgery on patients taking risperidone.

背景与目标： 目的：术中软性虹膜综合症（IFIS）与选择性a1肾上腺素能阻滞剂（尤其是坦索罗辛）的摄入密切相关。术中软性虹膜综合症也与使用其他具有拮抗作用的药物有关。
方法：我们确定长期接受抗精神病药利培酮治疗的患者在白内障手术期间表现出IFIS的典型特征。
结果：我们报告了2名服用利培酮的患者中有3只眼，其中白内障手术期间注意到IFIS的典型特征。
结论：利培酮是在精神病学实践中被广泛处方的药物，具有阻断作用以及对5-羟色胺2A受体的强亲和力。眼科医师应在接受利培酮治疗的患者进行白内障手术时意识到与IFIS的可能联系。

BACKGROUND & AIMS: OBJECTIVES:Second-generation antipsychotics (SGAs) increase appetite and weight, leading toward a metabolic syndrome. Risperidone and aripiprazole, the most widely used pediatric SGAs, have been studied predominantly in short-term clinical trials, where risperidone leads to a rapid weight increase and aripiprazole to a slower one, while long-term effects are not yet elucidated. Factors that may influence weight gain are likewise not clarified, although baseline weight, previous SGA exposure, pubertal status, and type of SGA have been suggested as moderators. We analyzed weight gain induced by risperidone and aripiprazole in a sample of pediatric outpatients enrolled into a 2-year observational study. METHODS:We assessed at several time points their body mass index (BMI)-Z scores (age and sex-corrected and referred to national norms). We used hierarchical mixed-effects modeling to design BMI-Z trajectories and observed the effects of several variables on determining them. RESULTS:The study group comprised of 127 patients, predominantly males (79%), of 12.6 years on average, treated with risperidone (81%) and aripiprazole (19%) for disruptive behavioral symptoms in patients with and without neurodevelopmental disorders. Overall, BMI-Z was 1.2 at first and 1.4 at last visit (no significant change). We could design four weight-change trajectories, determined by the factors: drug (risperidone/aripiprazole) and age status (children/adolescent). Additional factors not retained in the model but possibly explanatory include the previous duration of SGA treatment and a progressive patient-selection effect due to dropouts in this observational study. Risperidone treatment was associated with trends of BMI-Z increase in children and decrease in adolescents. Aripiprazole treatment was associated with significant BMI-Z increase, higher in children than in adolescents. Results are probably due to longer previous drug exposure in adolescents. CONCLUSIONS:Children were at risk of weight gain more than adolescents, for both risperidone and, of note, aripiprazole. Adolescents and patients with long previous drug exposure tend to reach stable BMI-Z, although in the range between excessive weight and obesity.

背景与目标： 目的：第二代抗精神病药（SGA）会增加食欲和体重，从而导致新陈代谢综合症。利培酮和阿立哌唑是最广泛使用的儿科SGA，主要是在短期临床试验中进行研究，其中利培酮导致体重迅速增加，阿立哌唑的体重增加较慢，而长期作用尚不清楚。尽管基线体重，先前的SGA暴露，青春期状态和SGA类型已被建议作为缓和剂，但仍未阐明可能影响体重增加的因素。我们分析了利培酮和阿立哌唑在一项为期2年的观察性研究中的儿科门诊样本中引起的体重增加。
方法：我们在几个时间点评估他们的体重指数（BMI）-Z得分（年龄和性别校正并参考国家规范）。我们使用分层混合效应建模来设计BMI-Z轨迹，并观察了几个变量对确定它们的影响。
结果：该研究组由127名患者组成，平均为男性（79％），平均为12.6岁，接受利培酮（81％）和阿立哌唑（19％）治疗具有和不具有神经发育障碍的患者的破坏性行为症状。总体而言，BMI-Z初次访问时为1.2，最后一次访问时为1.4（无明显变化）。我们可以设计四个由体重决定的体重变化轨迹：药物（利培酮/阿立哌唑）和年龄状态（儿童/青少年）。该模型中未保留的其他因素，但可能是解释性的，包括先前的SGA治疗持续时间以及由于该观察性研究中的辍学而导致的逐步患者选择效应。利培酮治疗与儿童BMI-Z升高和青少年BMI-Z升高趋势相关。阿立哌唑治疗与BMI-Z显着增加有关，儿童中的BMI-Z高于青少年。结果可能是由于青少年以前接触药物的时间更长。
结论：利培酮和阿立哌唑的患儿体重增加的风险均比青少年高。青少年和长期吸毒的患者倾向于达到稳定的BMI-Z，尽管介于体重过多和肥胖之间。

BACKGROUND & AIMS: :Treatment of Alzheimer's disease sometimes uses combinations of drugs because dementia is frequently associated with behavioral symptoms. Risperidone and donepezil are both metabolized through cytochrome P450 2D6 and 3A4, raising the possibility of drug interactions with combination therapy. The objective of this study was to determine whether significant drug interactions occur with concomitant administration of donepezil and risperidone. In an open-label, three-way crossover study, 24 healthy men were randomly assigned to receive 0.5 mg of risperidone twice daily, 5 mg of donepezil once daily, or both drugs for 14 consecutive days, followed by a 21-day washout period. The treatment ratios of AUC and associated 90% confidence intervals (CIs) for risperidone active moiety, defined as risperidone plus 9-hydroxyrisperidone (ratio = 110.2%; 90% CI = 103.7-117.2), and for donepezil (ratio = 97.1%; 90% CI = 90.0-103.6) were within the 80% to 125% of bioequivalence range. The treatment ratios of Cmax and associated 90% CIs for risperidone active moiety (ratio = 114.6%; 90% CI = 107.0-122.8) and for donepezil (ratio = 96.1%; 90% CI = 90.0-102.6) were also within the bioequivalence range. Therefore, no significant pharmacokinetic differences occurred in either risperidone active moiety or donepezil when given alone or in combination. Adverse events (predominantly headache, nervousness, and somnolence) were minor and comparable for all treatment groups. The results indicate that no clinically meaningful drug interactions occurred between risperidone 1 mg daily and donepezil 5 mg daily at steady state, and therefore no dosage adjustment is required when both drugs are combined with the dosage regimen studied. Additional investigations are warranted to determine the potential for interactions in elderly patients with dementia who may eliminate risperidone and donepezil more slowly and thus be more vulnerable to clinical drug interactions than the young healthy subjects examined in this study.

背景与目标： ：阿尔茨海默氏病的治疗有时会结合使用药物，因为痴呆症经常与行为症状相关。利培酮和多奈哌齐均通过细胞色素P450 2D6和3A4代谢，增加了药物与联合疗法相互作用的可能性。这项研究的目的是确定在与多奈哌齐和利培酮同时给药时是否发生显着的药物相互作用。在一项开放式，三方交叉研究中，随机分配24名健康男性，使其每天连续两次接受0.5 mg利培酮，每天一次5 mg的多奈哌齐或两种药物连续14天，随后为期21天的清除期。定义为利培酮加9-羟基利培酮的比例的利培酮活性部分的AUC和相关的90％置信区间（CIs）的治疗比率（比率= 110.2％; 90％CI = 103.7-117.2）和多奈哌齐（比率= 97.1％; 90％CI = 90.0-103.6）在生物等效性的80％到125％之间。利培酮活性成分（比率= 114.6％; 90％CI = 107.0-122.8）和多奈哌齐（比率= 96.1％; 90％CI = 90.0-102.6）的Cmax和相关90％CI的治疗率也在生物等效性之内范围。因此，单独或组合使用时，利培酮活性成分或多奈哌齐均未发生明显的药代动力学差异。不良事件（主要是头痛，神经质和嗜睡）轻微，在所有治疗组中均具有可比性。结果表明，稳定状态下每天1mg利培酮和5mg每天多奈哌齐之间没有发生临床上有意义的药物相互作用，因此，当两种药物与所研究的剂量方案联合使用时，无需调整剂量。与本研究中检查的年轻健康受试者相比，有必要进行额外的研究以确定老年痴呆症患者的相互作用潜力，这些老年痴呆症患者可能较慢地消除利培酮和多奈哌齐，因此更容易受到临床药物相互作用的影响。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the safety and efficacy of risperidone augmentation of lithium in preschool-onset bipolar disorder (BD) among youth who insufficiently respond to lithium monotherapy. METHOD:Thirty-eight subjects between the ages of 4 and 17 years (mean age = 11.37 +/- 3.8 years) with onset of BD in preschool years (manic or mixed episode) entered this 12-month trial. All subjects received lithium monotherapy. Patients who failed to adequately respond to lithium monotherapy after 8 weeks and those who relapsed after an initial response were given risperidone augmentation for up to 11 months. The Young Mania Rating Scale (YMRS) was the primary outcome measure. Response was defined as a > or =50% decrease from baseline. Additional data were collected on diagnostic comorbidity, family history, number of hospitalizations, perinatal risk factors, history of physical or sexual abuse, Child Depression Rating Scale-Revised (CDRS-R), Clinical Global Impression (CGI) scale for BD (CGI-BP), Children's Global Assessment Scale (C-GAS), and adverse medication effects. RESULTS:Of the 38 subjects treated with lithium monotherapy, 17 responded, whereas 21 required augmentation with risperidone. Response rate in the youths treated with lithium + risperidone was 85.7% (n = 18/21). Significant predictors of inadequate response to lithium monotherapy requiring augmentation were: (1) attention-deficit/hyperactivity disorder (ADHD), (2) severity at baseline, (3) history of sexual or physical abuse, and (4) preschool age. Combination treatment of lithium and risperidone was found to be safe and well tolerated. CONCLUSIONS:A substantial proportion of youth with a history of preschool-onset BD treated with lithium were either nonresponders or partial responders. Subsequent augmentation of lithium with risperidone in these cases was well tolerated and efficacious. Potential predictors of lithium nonresponse identified in this study may guide the choice of medications earlier in the treatment process.

背景与目标： 目的：本研究的目的是评估对锂单药治疗反应不佳的年轻人在学龄前发作的双相情感障碍（BD）中使用利培酮增强锂的安全性和有效性。
方法：38名年龄在4至17岁（平均年龄= 11.37 /-3.8岁），学龄前BD发作（躁狂或混合发作）的受试者参加了这个为期12个月的试验。所有受试者均接受锂单药治疗。在8周后对锂单药治疗没有充分反应的患者以及在初次反应后复发的患者给予利培酮增强治疗长达11个月。青年躁狂症评定量表（YMRS）是主要的结局指标。响应定义为与基线相比下降>或= 50％。收集了以下数据：诊断合并症，家族病史，住院次数，围产期危险因素，身体或性虐待史，修订的儿童抑郁量表（CDRS-R），BD的临床总体印象量表（CGI） BP），儿童全球评估量表（C-GAS）和药物不良反应。
结果：在接受锂单药治疗的38位受试者中，有17位有效，而21位需要使用利培酮进行增强。锂利培酮治疗的年轻人的缓解率为85.7％（n = 18/21）。对需要增加使用锂的单药治疗反应不足的重要预测因素包括：（1）注意缺陷/多动障碍（ADHD），（2）基线严重程度，（3）性或身体虐待史以及（4）学龄前儿童。锂和利培酮的联合治疗被发现是安全且耐受性良好的。
结论：相当一部分有锂治疗的学龄前性BD病史的青年是无反应者或部分反应者。在这些情况下，随后使用利培酮增加锂的耐受性和疗效良好。在这项研究中确定的锂无反应的潜在预测因素可能会在治疗过程的早期指导药物的选择。

BACKGROUND & AIMS: :Risperidone is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the cytochrome P450 enzymes CYP2D6 and 3A4. Its antipsychotic effect is assumed to be related to the active moiety, that is, the sum of risperidone and 9-hydroxyrisperidone. Both risperidone and 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp), a transport protein involved in drug absorption, distribution, and elimination. The aim of the present study was to evaluate the influence of polymorphisms in genes encoding CYP3A5 and P-gp (ABCB1) on the steady-state plasma levels of risperidone, 9-hydroxyrisperidone, and the active moiety, taking CYP2D6 genotype status into account. Forty-six white patients with schizophrenia treated with risperidone (1-10 mg/d) in monotherapy for 4-6 weeks were genotyped, and their plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. Dose-corrected plasma concentrations (C/D) of risperidone, 9-hydroxyrisperidone, and active moiety showed up to 68-, 9-, and 10-fold interindividual variation, respectively. Six patients carried 1 CYP3A5*1 allele and therefore were likely to express the CYP3A5 enzyme. The CYP3A5 genotype did not influence risperidone, 9-hydroxyrisperidone, or active moiety C/Ds. The CYP2D6 genotype in these 46 patients was again associated with risperidone C/D (P = 0.001) but not with 9-hydroxyrisperidone C/D or active moiety C/D, as previously shown by our group in 37 of these patients. Patients homozygous for the ABCB1 3435T/2677T/1236T haplotype had significantly lower C/Ds of 9-hydroxyrisperidone (P = 0.026) and active moiety (P = 0.028) than patients carrying other ABCB1 genotypes. In conclusion, our results confirmed the significant effect of CYP2D6 genotype on the steady-state plasma levels of risperidone and showed that ABCB1 polymorphisms have a moderate effect on those of 9-hydroxyrisperidone and the active moiety.

背景与目标： ：利培酮主要通过细胞色素P450酶CYP2D6和3A4代谢成其活性代谢物9-羟基利培酮。假定其抗精神病作用与活性部分有关，即利培酮和9-羟基利培酮的总和。利培酮和9-羟基利培酮都是P-糖蛋白（P-gp）的底物，P-gp是一种涉及药物吸收，分布和消除的转运蛋白。本研究的目的是在考虑CYP2D6基因型状态的情况下，评估CYP3A5和P-gp（ABCB1）编码基因多态性对利培酮，9-羟基利培酮和活性成分的稳态血浆水平的影响。对46例接受利培酮（1-10 mg / d）单一治疗4-6周的精神分裂症白人患者进行基因分型，并测定其血浆中利培酮和9-羟基利培酮的浓度。利培酮，9-羟基利培酮和活性部分的剂量校正血浆浓度（C / D）分别显示高达68倍，9倍和10倍的个体差异。 6名患者携带1个CYP3A5 * 1等位基因，因此可能表达CYP3A5酶。 CYP3A5基因型不影响利培酮，9-羟基利培酮或活性部分C / D。 CYP2D6基因型在这46例患者中再次与利培酮C / D相关（P = 0.001），但与9-羟基利培酮C / D或活性成分C / D不相关，正如我们小组中先前在这些患者中的37名所示。与携带其他ABCB1基因型的患者相比，纯合ABCB1 3435T / 2677T / 1236T单倍型的患者的9-羟基利培酮（C = 0.026）和活性部分（P = 0.028）的C / D显着降低。总之，我们的结果证实了CYP2D6基因型对利培酮的稳态血浆水平具有显着影响，并表明ABCB1多态性对9-羟基利培酮和活性成分的中度影响中等。

BACKGROUND & AIMS: BACKGROUND:Alzheimer's dementia (AD) occurs in 6 - 8% of persons older than 65 years. The prevalence increases to 30% among those 85 years or older. Among AD patients, the incidence of psychosis is 30 - 50%. Safe and appropriate use of psychotropic agents is a relevant clinical concern for this population. OBJECTIVE:This review addresses risks and potential benefits when risperidone is used for treating AD-associated psychosis. METHODS:Through literature review and clinical experience, the authors discuss the clinical efficacy, safety, and regulatory issues concerning risperidone treatment for this group of patients. CONCLUSION:Despite concerns about safety, risperidone remains a popular therapeutic choice for AD patients with psychosis. Subsets of these patients with more severe agitation and aggression may experience greater behavioral benefit.

背景与目标： 背景：阿尔茨海默氏痴呆症（AD）发生在6至8％的65岁以上的人群中。在85岁以上的人群中，患病率上升到30％。在AD患者中，精神病的发生率为30-50％。安全和适当使用精神药物是该人群的相关临床问题。
目的：本文综述了利培酮用于治疗AD相关性精神病的风险和潜在收益。
方法：通过文献综述和临床经验，作者讨论了有关利培酮治疗此组患者的临床疗效，安全性和监管问题。
结论：尽管担心安全性，利培酮仍然是AD精神病患者的流行治疗选择。这些躁动和攻击更为严重的患者亚群可能会获得更大的行为益处。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :We evaluated the inhibitory effects of the atypical antipsychotic drug risperidone on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Risperidone suppressed Kv currents in reversible and concentration-dependent manners with an apparent half-maximal effective concentration (IC50 value) of 5.54 ± 0.66 μM and a slope factor of 1.22 ± 0.07. The inactivation of Kv currents was significantly accelerated by risperidone. The rate constants of association and dissociation for risperidone were 0.25 ± 0.01 μM-1s-1 and 1.36 ± 0.14 s-1, respectively. Application of risperidone shifted the steady-state activation curve in the positive direction and the inactivation curve in the negative direction, suggesting that the risperidone-induced inhibition of Kv channels was mediated by effects on the voltage sensors of the channels. Application of train pulses at 1 and 2 Hz led to a progressive increase in the blockage of Kv currents by risperidone. In addition, the recovery time constants from inactivation were extended in the presence of risperidone, indicating that risperidone inhibited Kv channels in a use (state)-dependent manner. Pretreatment with the Kv1.5 subtype inhibitor reduced the inhibitory effects of risperidone on Kv channels. However, pretreatment with a Kv2.1 or Kv7.X subtype inhibitor did not affect the inhibitory effects of risperidone. Risperidone induced vasoconstriction and membrane depolarization. Based on these results, we conclude that risperidone inhibits Kv channels in a concentration-, time-, and state-dependent manners. Our results should be taken into consideration when using risperidone to study the kinetics of K+ channels in vascular smooth muscle.

背景与目标： ：我们评估了非典型抗精神病药利培酮对兔冠状动脉平滑肌细胞电压依赖性钾离子（Kv）通道的抑制作用。利培酮以可逆和浓度依赖性方式抑制Kv电流，表观最大有效浓度（IC50值）为5.54±0.66μM，斜率系数为1.22±0.07。利培酮显着加速了Kv电流的失活。利培酮的缔合和解离速率常数分别为0.25±0.01μM-1s-1和1.36±0.14s-1。利培酮的应用使稳态激活曲线向正方向移动，而灭活曲线向负方向移动，这表明利培酮诱导的Kv通道抑制作用是通过对通道电压传感器的影响来介导的。施加1和2 Hz的脉冲脉冲会导致利培酮对Kv电流的阻滞作用逐渐增加。另外，在存在利培酮的情况下延长了失活的恢复时间常数，这表明利培酮以使用（状态）依赖的方式抑制了Kv通道。用Kv1.5亚型抑制剂预处理可降低利培酮对Kv通道的抑制作用。但是，用Kv2.1或Kv7.X亚型抑制剂预处理不会影响利培酮的抑制作用。利培酮引起的血管收缩和膜去极化。基于这些结果，我们得出结论，利培酮以浓度，时间和状态依赖性方式抑制Kv通道。当使用利培酮研究血管平滑肌中K通道的动力学时，应考虑我们的结果。

BACKGROUND & AIMS: :Risperidone is a potent antagonist of both dopamine (D2) and serotonin (5-HT2) receptors, demonstrating improvement of both positive and negative symptoms and a lower propensity for inducing extrapyramidal symptoms (EPS) than typical neuroleptics. Its most common side-effects, found in the Canadian multi-centre trial (Chouinard et al., 1993), were agitation, anxiety, insomnia, EPS, headache and nausea, in order of frequency. With regard to endocrine effects, risperidone causes an increase in prolactin levels similar to that of other neuroleptics (Claus et al., 1992). In open clinical trials (De Cuyper, 1991), the overall incidence of risperidone-induced endocrine side-effects was quite low: 2.9 % for amenorrhoea and 1-2% for galactorrhoea. However, it is assumed that the incidence can vary depending upon the characteristics of patients and the drug regimen, i.e. dosage and titration schedule. In our experience, hyperolactinaemia is likely to occur when prescribing risperidone to female or first-onset psychotic patients: we are reporting 5 cases of risperidone-induced hyperprolactinaemia with these characteristics.

背景与目标： ：利培酮是多巴胺（D2）和5-羟色胺（5-HT2）受​​体的有效拮抗剂，与典型的精神安定药相比，具有积极和消极症状的改善，诱发锥体外系症状（EPS）的可能性更低。在加拿大的多中心试验中（Chouinard等，1993）发现，其最常见的副作用是躁动，焦虑，失眠，EPS，头痛和恶心（按频率排序）。关于内分泌作用，利培酮引起的催乳素水平增加，类似于其他精神安定药（Claus et al。，1992）。在公开的临床试验中（De Cuyper，1991），利培酮引起的内分泌副作用的总发生率很低：闭经为2.9％，乳汁为1-2％。但是，假定发病率可以根据患者的特征和药物治疗方案，即剂量和滴定时间表而变化。根据我们的经验，当向女性或初次发作的精神病患者开具利培酮处方时，可能会发生高泌乳素血症：我们报告了5例具有这些特征的利培酮引起的高催乳素血症。

BACKGROUND & AIMS: OBJECTIVE:To examine whether subjective well-being and craving for cannabis were different in patients with schizophrenia or related disorders treated with either olanzapine or risperidone. METHOD:A 6-week, double-blind, randomized trial of olanzapine and risperidone was carried out in 128 young adults with recent onset schizophrenia or related disorders. Primary efficacy measures were the mean baseline-to-endpoint change in total scores on the Subjective Well-Being under Neuroleptics scale, the Obsessive-Compulsive Drug Use Scale, the Drug Desire Questionnaire, and the cannabis use self-report. An analysis of covariance was used to test between-group differences. RESULTS:Estimated D(2) receptor occupancy did not differ between olanzapine (n = 63) and risperidone (n = 65). Similar improvements in subjective well-being were found in both groups. In the comorbid cannabis-using group (n = 41, 32%), a similar decrease in craving for cannabis was found in both treatment conditions. CONCLUSIONS:Both olanzapine and risperidone were associated with improved subjective well-being. No evidence was found for a differential effect of olanzapine or risperidone on subjective experience or on craving for cannabis in dosages leading to comparable dopamine D(2) occupancy. CLINICAL TRIAL REGISTRATION NUMBER:ISRCTN46365995.

背景与目标： 目的：研究用奥氮平或利培酮治疗的精神分裂症或相关疾病患者的主观幸福感和对大麻的渴望是否不同。
方法：对128名患有近期精神分裂症或相关疾病的年轻人进行了为期6周的双盲，随机试验的奥氮平和利培酮。主要疗效指标是在抗精神病药量表，强迫性药物使用量表，药物欲望调查表和大麻使用自我报告下，主观幸福感总得分的平均基线到终点变化。协方差分析用于检验组间差异。
结果：奥氮平（n = 63）和利培酮（n = 65）之间的估计D（2）受体占有率没有差异。两组的主观幸福感都有类似的改善。在合并使用大麻的组（n = 41，32％）中，在两种治疗条件下都发现了对大麻的渴望减少。
结论：奥氮平和利培酮均与主观幸福感改善有关。没有证据表明奥氮平或利培酮对主观经验或对大麻的渴望导致可比的多巴胺D（2）占有量有差异。
临床试验注册号：ISRCTN46365995。

BACKGROUND & AIMS: :The antipsychotics haloperidol and risperidone are widely used in the therapy of schizophrenia. The former drug mainly acts on the dopamine (DA) D(2) receptor whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly in the neurons of striatal and limbic structures. Recent evidence suggests that neurotrophins might also be involved in antipsychotic action in the central nervous system (CNS). We have previously reported that haloperidol and risperidone significantly affect brain nerve growth factor (NGF) level suggesting that these drugs influence the turnover of endogenous growth factors. Brain-derived neurotrophic factor (BDNF) supports survival and differentiation of developing and mature brain DA neurons. We hypothesized that treatments with haloperidol or risperidone will affect synthesis/release of brain BDNF and tested this hypothesis by measuring BDNF and TrkB in rat brain regions after a 29-day-treatment with haloperidol or risperidone added to chow. Drug treatments had no effects on weight of brain regions. Chronic administration of these drugs, however, altered BDNF synthesis or release and expression of TrkB-immunoreactivity within the brain. Both haloperidol and risperidone significantly decreased BDNF concentrations in frontal cortex, occipital cortex and hippocampus and decreased or increased TrkB receptors in selected brain structures. Because BDNF can act on a variety of CNS neurons, it is reasonable to hypothesize that alteration of brain level of this neurotrophin could constitute one of the mechanisms of action of antipsychotic drugs. These observations also support the possibility that neurotrophic factors play a role in altered brain function in schizophrenic disorders.

背景与目标： ：抗精神病药氟哌啶醇和利培酮广泛用于精神分裂症的治疗。前一种药物主要作用于多巴胺（DA）D（2）受体，而利培酮结合到DA和5-羟色胺（5HT）受体上，特别是在纹状体和边缘结构的神经元中。最近的证据表明，神经营养蛋白也可能参与中枢神经系统（CNS）的抗精神病作用。我们以前曾报道氟哌啶醇和利培酮显着影响脑神经生长因子（NGF）的水平，表明这些药物影响内源性生长因子的周转率。脑源性神经营养因子（BDNF）支持发育中和成熟的脑DA神经元的存活和分化。我们假设用氟哌啶醇或利培酮治疗会影响脑BDNF的合成/释放，并通过将氟哌啶醇或利培酮添加到食物中29天后测量大鼠脑区的BDNF和TrkB来检验这一假设。药物治疗对大脑区域的重量没有影响。但是，这些药物的长期服用改变了BDNF的合成或脑内TrkB免疫反应性的释放和表达。氟哌啶醇和利培酮都显着降低额叶皮质，枕叶皮质和海马中的BDNF浓度，并减少或增加选定脑结构中的TrkB受体。由于BDNF可以作用于多种CNS神经元，因此有理由假设这种神经营养蛋白的脑水平改变可能构成抗精神病药的作用机制之一。这些观察结果也支持神经营养因子在精神分裂症疾病的脑功能改变中起作用的可能性。

BACKGROUND & AIMS: :The objective of the study is to investigate whether dopamine D2 receptor occupancy by risperidone and plasma levels over time can account for therapeutic efficacy and the latency period to response. Thirty-eight examinations with (123)I-IBZM single photon emission computed tomography were performed on 22 patients with schizophrenia, at diagnosis, 48 h after starting risperidone treatment and at a stable dose. Risperidone plasma levels were determined and psychopathologic evaluations (Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale) were carried out. No differences in the striatal/occipital (S/O) ratio or plasma levels were found between examinations at the 48-h time point and when a stable dose level had been established, so these parameters could not account for the latency period required for clinical response. D2 receptor occupancy at 48 h correlated positively with clinical improvement after 2 weeks of treatment. Therefore, if these results are confirmed, D2 receptor occupancy at the beginning of treatment with risperidone may be a predictor of subsequent clinical response.

背景与目标： ：该研究的目的是调查利培酮和血浆中多巴胺D2受体的占有率随时间的推移是否可以解释治疗效果和反应的潜伏期。对22例精神分裂症患者进行了38项（123）I-IBZM单光子发射计算机断层扫描检查，诊断时，开始使用利培酮治疗后48小时且剂量稳定。确定利培酮的血浆水平，并进行心理病理学评估（简明精神病评定量表，阳性和阴性综合征量表）。在48小时的时间点和建立稳定剂量水平后的两次检查之间，没有发现纹状体/枕骨（S / O）比或血浆水平存在差异，因此这些参数无法解释临床所需的潜伏期回复。治疗2周后，D2受体在48小时的占有率与临床改善呈正相关。因此，如果这些结果得到证实，利培酮治疗开始时D2受体的占有率可能是随后临床反应的预测指标。

BACKGROUND & AIMS: :Risperidone (RSP) and its major active metabolite, 9-hydroxy-risperidone (paliperidone, PALI), are substrates of the drug transporter P-glycoprotein (P-gp). The goal of this study was to examine the in vitro effects of RSP and PALI on P-gp-mediated transport. The intracellular accumulation of rhodamine123 (Rh123) and doxorubicin (DOX) were examined in LLC-PK1/MDR1 cells to evaluate P-gp inhibition by RSP and PALI. Both compounds significantly increased the intracellular accumulation of Rh123 and DOX in a concentration-dependent manner. The IC(50) values of RSP for inhibiting P-gp-mediated transport of Rh123 and DOX were 63.26 and 15.78 microM, respectively, whereas the IC(50) values of PALI were >100 microM, indicating that PALI is a less potent P-gp inhibitor. Caco-2 and primary cultured rat brain microvessel endothelial cells (RBMECs) were utilized to investigate the possible influence of RSP on intestinal absorption and blood-brain barrier (BBB) transport of coadministered drugs that are P-gp substrates. RSP, 1-50 microM, significantly enhanced the intracellular accumulation of Rh123 in Caco-2 cells by inhibiting P-gp activity with an IC(50) value of 5.87 microM. Following exposure to 10 microM RSP, the apparent permeability coefficient of Rh123 across Caco-2 and RBMECs monolayers was increased to 2.02 and 2.63-fold in the apical to basolateral direction, but decreased to 0.37 and 0.21-fold in the basolateral to apical direction, respectively. These data suggest that RSP and PALI, to a lesser extent, have a potential to influence the pharmacokinetics and hence the pharmacodynamics of coadministered drugs via inhibition of P-gp-mediated transport. However, no human data exist that address this issue. In particular, RSP may interact with its own active metabolite PALI by promoting its brain concentration through inhibiting P-gp-mediated efflux of PALI across endothelial cells of the BBB.

背景与目标： ：利培酮（RSP）及其主要活性代谢物9-羟基-利培酮（paliperidone，PALI）是药物转运蛋白P-糖蛋白（P-gp）的底物。这项研究的目的是检查RSP和PALI对P-gp介导的转运的体外作用。在LLC-PK1 / MDR1细胞中检查了若丹明123（Rh123）和阿霉素（DOX）的细胞内蓄积情况，以评估RSP和PALI对P-gp的抑制作用。两种化合物均以浓度依赖性方式显着增加Rh123和DOX的细胞内积累。 RSP抑制P-gp介导的Rh123和DOX转运的IC（50）值分别为63.26和15.78 microM，而PALI的IC（50）值> 100 microM，表明PALI是一种较弱的P -gp抑制剂。 Caco-2和原代培养的大鼠脑微血管内皮细胞（RBMEC）用于研究RSP对共同给药的P-gp底物的肠道吸收和血脑屏障（BBB）转运的可能影响。 1-50 microM的RSP通过抑制P-gp活性以5.87 microM的IC（50）值显着增强Caco-2细胞中Rh123的细胞内积累。暴露于10 microM RSP后，Rh123在Caco-2和RBMECs单层的表观通透性系数在根尖到基底外侧方向分别增加到2.02和2.63倍，但在根尖到基底外侧方向分别降低到0.37和0.21倍，分别。这些数据表明，RSP和PALI在较小程度上具有通过抑制P-gp介导的转运来影响共同给药药物的药代动力学和药效学的潜力。但是，不存在解决此问题的人员数据。特别是，RSP可能通过抑制P-gp介导的PALI跨BBB内皮细胞的流出而促进其脑部集中，从而与其自身的活性代谢产物PALI相互作用。