Amisulpride is an “atypical” antipsychotic associated with low weight gain

Rationale It is possible that amisulpride, with its unique receptor binding profile, is not associated with significant weight gain, a serious side effect of most atypical antipsychotic drugs. While most atypicals have a high affinity for both dopamine and serotonin receptors, amisulpride has only dopamine receptor action.Objectives To analyse the weight gain associated with amisulpride.Methods A pooled database of prospective randomised amisulpride studies was analysed. The mean weight gain after 10 weeks of treatment was estimated by regression analysis.Results Eleven studies with a total of 1422 patients were pooled, providing 1392 patients who were eligible for evaluation. In the main analysis of all effective doses (50–1200 mg/day) the mean weight gain associated with amisulpride at 10 weeks was 0.8 kg, 95% CI (0.48–1.18). Linear regression showed no dependence of weight gain on daily dose levels (P=0.7). When patients with mean daily doses below 400 mg/day were excluded in a sensitivity analysis, the mean weight gain at ten weeks was again 0.80 kg, 95% CI (0.47–1.16) with n=874. The mean weight gain at study endpoints in 1-year studies was 1.4 kg, 95% CI (0.85–1.90), n=548.Conclusion Amisulpride is an atypical antipsychotic associated with low weight gain.     

Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology – a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist

The benzamide amisulpride (ASP) is a selective D₂-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D₂-like, D₁-like and 5-HT₂ receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D₁-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi-center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: −42%; FPX: −32%) and SAPS (ASP: −78%; FPX: −65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D₁-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability. Received: 12 May 1997/Final version: 22 September 1997     

Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol

Amisulpride is a substituted benzamide with high selectivity for dopaminergic D₂ and D₃ receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism. Received: 13 December 1996/Final version: 12 March 1997     

维持治疗期间不同剂量氨磺必利对精神分裂症认知功能及临床疗效的影响

目的:探讨维持治疗期间不同剂量氨磺必利对精神分裂症认知功能及远期疗效的影响。方法:采用2012年3月-2013年3月在我院住院采用氨磺必利治疗并获得临床痊愈的精神分裂症患者,共96例。随机分为全剂量组和半剂量组,急性期治疗3个月后,全剂量组(46例)维持原治疗剂量600~800mg/d;半剂量组(50例)给予原治疗量的一半作维持量300~400mg/d,纳入病例在出院后持续随访1年,采用韦氏成人智力量表(WAIS)、临床记忆量表评价认知功能,采用阳性与阴性症状量表(PANSS)、大体评定量表(GAS)来衡量评价临床疗效。结果:1年随访后两组认知功能比较差异显著,WAIS量表:言语智商、操作智商、总智商(t=6.1276,3.2526,5.1423;P<0.05);记忆量表:联想学习、图像自由回忆、人像特点回忆及记忆商数(t=3.0972,3.3938,3.0565,2.8937;P<0.05)。两组临床疗效比较:PANSS总分(t=3.6915,P<0.05);GAS量表评分(t=9.5153,P<0.05);1年累计缓解率分别为82.2%和60.4%(χ2=5.32,P<0.05);复发率分别为15.22%和34.00%(χ2=4.51,P<0.05)。副作用发生率分别为45.65%和34.00%(χ2=1.36,P>0.05)。结论:采用氨磺必利全治疗剂量维持治疗对认知功能改善明显,远期疗效较好、复发率较少。     

氨磺必利治疗抑郁症的临床对照研究

目的 探讨氨磺必利治疗抑郁症的有效性及安全性.方法 选择符合ICD-10抑郁症诊断标准的患者43例,随机分为氨磺必利组(研究组)21例和帕罗西汀组(对照组)22例,均治疗8周.于治疗前及治疗后第1、2、4、6、8周末采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效,以及治疗中需处理的不良反应症状量表(TESS)评定不良反应.结果 治疗后第1、2、4、6、8周末两组HAMD、HAMA评分均较治疗前显著降低(P＜0.01);治疗后第1、2周末研究组HAMD、HAMA评分显著低于对照组(P＜0.05),治疗后第4、6、8周末两组HAMD、HAMA评分比较无显著性差异(P＞0.05),研究组不良反应发生率52.38％,对照组不良反应发生率50.00％,两组相比无统计学意义(P＞0.05).结论 氨磺必利治疗抑郁症的疗效、安全性与帕罗西汀相当.     

氨磺必利与利培酮治疗首发精神分裂症的对照研究

目的比较氨磺必利与利培酮治疗首发精神分裂症的疗效和安全性。方法按就诊先后顺序将首发精神分裂症患者分为研究组和对照组,分别给予氨磺必利和利培酮治疗8周。于治疗前及治疗后第4、8周末采用阳性与阴性综合征量表（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）评定患者的不良反应。结果治疗后第4、8周末,两组PANSS量表总分及分量表评分较治疗前均有显著降低（P〈0．05,P〈0．01）;研究组有效率93．8％,显效率71．9％;对照组有效率为90．6％,显效率68．8％,两组比较无显著性差异（P〉0．05）。研究组和对照组药物不良反应均较少。结论氨磺必利是一种安全有效的抗精神病药物,对治疗首发精神分裂症疗效与利培酮相当。     

Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine

Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups.     

氨磺必利治疗精神分裂症的疗效和安全性

目的 探讨氨磺必利治疗精神分裂症的疗效和安全性.方法 对45例成人精神分裂症患者进行为期12用的氨磺必利系统治疗,在治疗期间定期进行PANSS,TESS,CGI评定以及血常规、生化系列、心电图检查.结果 治疗前后PANSS,CGI评分均有显著性差异(P＜0.000).最常见的不良反应是EPS和催乳素升高.结论 氨磺必利能有效治疗精神分裂症,无严重不良反应,安全性高.     

氨磺必利在精神分裂症中的研究进展

氨磺必利作为第二代抗精神病药物,在治疗精神分裂症阳性和阴性症状,以及抗抑郁方面都有明确的疗效.本文就临床应用、作用机制、药代动力学特点、不良反应等方面对其作一综述.     

Identification of photodegradation product of amisulpride by ultra-high-pressure liquid chromatography-DAD/ESI-quadrupole time-of-flight-mass spectrometry

Photostability of amisulpride under UVA irradiation in methanol solution was investigated and structural elucidation of its photodegradation products was performed. For the purpose of the quantitative and qualitative analysis of amisulpride and the stress degradation products elucidation, the reversed phase UHPLC-DAD system coupled with accurate mass hybrid ESI-Q-TOF mass spectrometer was used. During one run (10 min) with the use of auto MS/MS mode all essential data for the determination of photodegradation kinetics and for the structural formulas elucidation of the products was collected. Four degradation products were found and their masses with high accuracy (0.53-3.05 ppm) and formulas were obtained - 258.0666 (C₁₀H₁₄N₂O₄S), 367.1564 (C₁₇H₂₅N₃O₄S), 341.1412 (C₁₅H₂₃N₃O₄S) and 385.1665 (C₁₇H₂₇N₃O₅S). For all the analyzed compounds MS/MS fragmentation spectra were obtained (collision energy 19.8-26.1 V) allowing structural elucidation of unknown degradation products and indicating photodegradation pathways of amisulpride. UHPLC-DAD/ESI-Q-TOF system was found to be a powerful analytical tool for the fast and accurate stability analysis of pharmaceutical substances.