10种抗精神病药物对多巴胺D2受体占有率的模拟分析

目的 模拟分析10种抗精神病药物氟哌啶醇（haloperidol）、舒必利（sulpiride）、美哌隆（melperone）、氯氮平（clozapine）、喹硫平（quetiapine）、利培酮（risperidone）、齐拉西酮（ziprasidone）、瑞莫必利（remoxipride）、氨磺必利（amisulpride）、雷氯必利（raclopride）口服给药后在人体内对多巴胺D₂受体（DRD₂）占有的时间过程。方法 通过对10种抗精神病药物的口服给药和静脉给药的药动学数据模拟计算获取建模的药动学（PK）参数;通过已发表的文献数据计算获取10种抗精神病药物的结合动力学（BK）参数和细胞内DRD₂受体合成动力学（TK）参数;基于获取的PK、BK、TK参数建立10种抗精神病药物的DRD₂受体占有率数学计算模型（PK-BK-TK模型）。结果 已上市的9种（不包含雷氯必利）抗精神病药物在临床推荐剂量下对DRD₂的最大受体占有率均在65%以上,预测的DRD₂受体占有率曲线与其临床药效持续时间有良好的一致性;雷氯必利的合理给药剂量为2mg。结论 利用PK-BK-TK数学模型能准确预测抗精神病药物口服后在人体内对DRD₂受体的占有过程。该模型可为评估化合物在体内拮抗DRD₂受体的活性与潜在毒性提供一种新的研究思路和方法。     

氨磺必利与利培酮治疗精神分裂症对照研究

目的：观察氨磺必利治疗精神分裂症的临床疗效与安全性。方法将60例首发精神分裂症患者,随机分为氨磺必利组30例,利培酮组30例,疗程8周。采用阳性与阴性症状量表（ PANSS ）评定疗效,采用副反应量表（ TESS ）评定治疗中出现的不良反应。结果氨磺必利组的治疗总有效率为83.33%,利培酮组为80.00%,两组疗效差异无统计学意义（ P＞0.05）;氨磺必利组的体重增加明显少于利培酮组（ P〈0.05）。结论氨磺必利与利培酮治疗精神分裂症疗效相当,且氨磺必利引起体重增加数例明显较少,值得临床推广。     

国产氨磺必利与丙咪嗪治疗迟滞性抑郁症的临床对照研究

目的探讨国产氨磺必利治疗迟滞性抑郁症的疗效和安全性。方法将162例迟滞性抑郁患者随机分为观察组(国产氨磺必利)和对照组(丙咪嗪),治疗12周后对疗效、不良反应发生率、治疗依从性及随访1年复发率等数据进行组间比较及统计学分析。结果观察组研究对象的痊愈率和总有效率分别为39.0%和91.4%与对照组的38.3%和88.9%进行组间比较,观察组具有一定优势,但差异无统计学意义(P>0.05);随访1年复发率的比较中,观察组优于对照组,且差异有统计学意义(P<0.05);观察组研究对象的不良发应率为14.8%,低于对照组的23.5%,且差异有统计学意义(P<0.05);在治疗依从性的比较中,观察组显著高于对照组,且差异有统计学意义(P<0.05)。结论国产氨磺必利在迟滞性抑郁症的治疗中具有疗效显著,安全性高,复发率低,治疗依从性高等优势,具有重要的临床价值,适于临床推广使用。     

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.     

氨磺必利与奥氮平治疗女性精神分裂症对照研究

目的：探讨氨磺必利与奥氮平治疗女性精神分裂症的临床疗效和安全性。方法将50例女性精神分裂症患者随机分为两组,研究组口服氨磺必利治疗,对照组口服奥氮平治疗,观察6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。结果治疗2周末起两组阳性与阴性症状量表总分及各因子分均较治疗前呈持续性下降（ P＜0.05或0.01）,治疗6周末研究组显效率59.1％、有效率81.8％,对照组分别为65.2％、86.9％,两组比较差异无显著性（P＞0．05）。两组总体不良反应发生率比较差异无显著性（P＞0．05）,但不良反应表现形式有所不同。结论氨磺必利治疗女性精神分裂症疗效显著且与奥氮平相当,安全性高,依从性好。     

Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation

Abstract

Objectives. Previous publications demonstrated substitute benzamides as effective agents in treatment of clozapine-induced sialorrhea (CIS). The aim of this study was to compare efficacy of amisulpride and moclobemide (both from the substitute benzamide group) in controlling, or at least minimizing, CIS. Methods. The study was designed as a 6-week, two-center, fixed-dose, comparison study of 400 mg/day of amisulpride versus 300 mg/day of moclobemide as an adjunctive treatment in 53 schizophrenia and schizoaffective disorder patients (diagnosed according to DSM-IV) suffering from CIS. The patients were treated with each medication during 2 weeks, followed by a washout period of 2 weeks. Primary outcome measures included the reduction in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Secondary outcomes included the Positive and Negative Syndrome Scale (PANSS), Manic State Assessment Scale, and Extrapyramidal Symptom Rating Scale (ESRS). Results. Both amisulpride and moclobemide were very effective in reducing CIS. Almost 74% of patients treated with amisulpride and 83% of patients treated with moclobemide showed some level of improvement on NHRS. Only in one patient treated with amisulpride, CIS worsened. Conclusions. Both medications were safe and effective as treatment of CIS. Although moclobemide exceeded amisulpride in antisalivation activity, treatment of CIS with amisulpride leads to improvement in psychotic symptoms.     

2019—2022年漯河市中心医院西城分院抗精神病药的使用情况分析

目的 分析漯河市中心医院西城分院2019—2022年抗精神病药物的用药情况,为临床合理用药提供参考。方法 采用回顾性研究方法,对漯河市中心医院西城分院2019—2022年抗精神病药物的销售金额、用药频度（DDDs）、排序比（B/A）和日均费用（DDC）进行统计分析。结果 抗精神病药物的销售金额先增长后下降,非典型抗精神病药物销售金额占比始终较高;DDDs呈逐年上涨趋势,阿立哌唑和奥氮平一直占据销售金额和DDDs的前2位;DDC值变化较大,奥氮平、氨磺必利等高价品种的DDC值下降明显,而一些低价品种DDC则略有上涨;氨磺必利、奥氮平和阿立哌唑的B/A值变动较大,2022年所有抗精神病药物B/A值均接近1。结论 该院抗精神病药的使用情况较为合理,临床治疗以疗效好、不良反应少的非典型抗精神病药为主,特别是阿立哌唑和奥氮平,使用频度最高。氨磺必利和喹硫平用药频度增幅明显。     

高效液相色谱法测定人血浆中氨磺必利的浓度

目的：建立测定人血浆中氨磺必利浓度的高效液相色谱法。方法：以Diamonsil^TM C18（150mm×4．6mm，5μm）为色谱柱，流动相为0．03mol·L^-1磷酸二氢钾（调pH6．4）-乙腈（82：18），流速为1．0mL·min^-1，柱温40℃，检测波长为275mm。以醋酸乙酯-二氯甲烷（80：20）为提取剂。结果：氨磺必利1000．0，400．0，10．0μg·L^-1 3种质量浓度平均回收率分别为97．63％，98．71％，100．29％，日内、日间差RSD均低于8％（n=5）；分析方法的最低检测浓度为10．0μg·L^-1；线性范围10．0～1000．0μg·L^-1。回归方程C=136．03 F-3．25，r=0．9996（n=9）。结论：本法灵敏、准确、简单、快速，可用于临床血药浓度监测和药动学研究。