精神分裂症患者服用氨磺必利后血药浓度与临床疗效的关系

目的 探讨氨磺必利对治疗精神分裂症患者血药浓度与临床疗效之间的相关性,从而确定氨磺必利更安全、有效的治疗剂量.方法 对90例单一使用氨磺必利治疗精神分裂症的患者,于治疗前及治疗后2、4、8周采用高效液相色谱法测定血药浓度,同时采用阳性与阴性症状量表（PANSS）、治疗中出现的症状量表（TESS）分别评定疗效和不良反应,并进行相关性分析.结果 加标血浆氨磺必利10、400、100μg·mL-1的日内变化回收率分别为100.18%、97.53%、97.71%,日内、日间差RSD均低于8%（n=6）;相同剂量不同性别、年龄患者的血药浓度无明显统计学意义（P＞0.05）.氨磺必利（1日800～1200mg）治疗2、4、8周后的血药浓度分别为220.39±142.56nmol·L-1、310.24±154.98nmol·L-1和336.36±104.25nmol·L-1.氨磺必利的血浓度与临床疗效有明显的相关性.结论 氨磺必利治疗精神分裂症时,其剂量在1日800～1200mg,血药浓度在220～336nmol·L-1时更安全有效.     

氨磺必利与利培酮治疗首发精神分裂症的随机双盲双模拟平行对照试验

目的：探讨氨磺必利与利培酮治疗精神分裂症的疗效及安全性。方法：采用随机、双盲、双模拟、平行对照试验方法,将34例符合诊断标准的首发精神分裂症患者随机分为氨磺必利组和利培酮组,每组17例。氨磺必利和利培酮的治疗剂量分别为800～1 200 mg·d~（-1）和2～6 mg·d~（-1）。疗程均为8周。于治疗前及治疗第1,2,4,8周末采用阳性和阴性症状评定量表（PANSS）评定疗效,采用治疗中出现的症状量表（TESS）及实验室检查来评价安全性。结果：治疗后第2,4,8周末,两组PANSS总分较治疗前均显著降低（P〈0.05）;氨磺必利组和利培酮组总有效率分别为88.2%和82.4%,差异无统计学意义（P〉0.05）。两组不良反应发生率比较差异亦无统计学意义（P〉0.05）。结论：氨磺必利和利培酮对治疗精神分裂症的疗效相当,不良反应轻,值得临床应用。     

不同剂量阿立哌唑对氨磺必利致女性精神分裂症患者催乳素升高的影响

目的:探讨小剂量阿立哌唑对氨磺必利所致血清催乳素升高的影响。方法:随机选择门诊和住院的148例女性精神分裂症患者以氨磺必利治疗8周,随机分为氨磺必利组(对照组)、氨磺必利+5mg阿立哌唑组(研究组1)和氨磺必利+10mg阿立哌唑组(研究组2),每组61例,继续治疗8周;分别于治疗前和治疗8周末、16周末行阳性与阴性症状量表(PANSS)评分、测定血清催乳素(Prol)水平,于治疗8周末、16周末行副反应量表(TESS)评分,比较治疗前后各测量值的变化。结果:治疗8周末、16周末3组PANSS评分均较治疗前明显下降(P0.001),16周末两研究组均较对照组明显下降(P=0.039、P=0.029);3组TESS评分在治疗8周末、16周末组间差异均无统计学意义(P0.05)。3组催乳素治疗后均大幅上升,组内比较差异均有显著性(P0.001);治疗16周末组间差异有统计学意义(P=0.047),其中研究组2与对照组比较差异有统计学意义(P=0.012)。结论:10mg阿立哌唑可能会提高氨磺必利治疗女性精神分裂症患者的疗效、降低催乳素水平,但不会减少副作用。     

Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine functions in healthy volunteers

Rationale In a previous study in healthy volunteers, the anti-Parkinsonian drug pramipexole caused sedation and pupil dilatation, consistent with the stimulation of inhibitory D₂/D₃ autoreceptors on the ventral tegmental area dopaminergic neurones. The sedation may be related to the removal of the dopaminergic excitation of the locus coeruleus (via the meso-coerulear pathway), whereas the pupil dilatation may be due to the removal of the dopaminergic excitation of the Edinger–Westphal nucleus (via a putative meso-pupillomotor pathway).Objectives We investigated the hypothesis that amisulpride, a D₂/D₃ receptor antagonist, would have effects opposite to those of pramipexole on alertness, pupillary and endocrine functions.Materials and methods Pramipexole (0.5 mg), amisulpride (50 mg), and their combination were administered to 16 healthy males in a balanced, cross-over, double-blind design. Tests included measures of alertness (Pupillographic Sleepiness Test, critical flicker fusion frequency, visual analogue scales), pupillary functions (resting pupil diameter, light and darkness reflex responses), non-pupillary autonomic functions (heart rate, blood pressure, salivation, core temperature), and endocrine functions [blood concentrations of prolactin, growth hormone (GH) and thyroid stimulating hormone (TSH)]. Data were analysed by ANOVA.Results Pramipexole reduced alertness and pupillary light reflex response amplitude, tended to reduce core temperature, reduced prolactin levels and increased GH levels. Amisulpride reduced pupil diameter, increased the amplitude of the light reflex response and prolactin and TSH levels.Conclusions The opposite effects of pramipexole and amisulpride on alertness, pupillary function and pituitary hormone levels are consistent with their interactions with inhibitory D₂/D₃ receptors on VTA neurones and in the tuberoinfundibular system.     

A Double-blind,Randomised Comparative Trial of Amisulpride Versus Olanzapine in the Treatment of Schizophrenia: Short-term Results at Two Months

Summary

Objective: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.

Design and setting: A multinational, double-blind randomised clinical trial.

Patients and treatment:Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800?mg/d) or olanzapine (5-20?mg/d).

Main outcome measures: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.

Results: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7?±?3.9?kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9?±?3.2?kg, p?<?0.0001).

Conclusions: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.     

氨磺必利与舒必利治疗成年女性精神分裂症临床对比探讨

目的：探讨成年女性精神分裂症应用氨磺必利与舒必利的效果，以丰富临床治疗经验。方法随机选择该院2013年6月-2014年6月接收并确诊的精神分裂症的成年女性患者100例，根据入院治疗顺序随机分成对照组与观察组各50例，对照组通过舒必利治疗，观察组则通过氨磺必利予以治疗，经8周治疗后，统计两组患者的治疗总有效率及不良反应发生率，并将结果进行对比。结果经治疗后，患者的临床症状均有明显的改善与缓解，观察组治疗的总有效率为86.00%，对照组的为84.00%，比较差异无统计学意义(P>0.05)；另外，经治疗后，两组的PANSS评分都显著低于治疗前的评分(P<0.05)，但两组治疗后的PNASS评分比较差异无统计学意义(P>0.05)。观察组中5例治疗期间出现不良反应，不良反应率10.00%，对照组中13例不良反应，不良反应率26.00%，两组对比差异具有统计学意义(P<0.05)。结论成年女性精神分裂症应用氨磺必利与舒必利治疗效果相当，但是舒必利的不良反应率偏高，在临床治疗中应谨慎用药。     

氨磺必利的药理学进展与临床应用评价

目的:介绍抗精神病新药氨磺必利的药理学研究进展与临床应用概况,并评价其疗效,以指导临床正确、合理地个体化选择用药。方法:对近期国内外相关文献进行分析与评价。结果:氨磺必利具有较强的抗精神病作用,低剂量时缓解阴性症状,高剂量时治疗阳性症状,具有较高的临床疗效和较好的耐受性。结论:氨磺必利可作为治疗精神分裂症的一线药物应用于临床。     

Amisulpride-induced hyperprolactinemia is reversible following discontinuation

BACKGROUND: Although amisulpride is considered to be a prolactin-raising atypical antipsychotic drug, a limited number of studies have documented the extent of its prolactin-elevating properties. In the present study the effect of amisulpride on plasma levels of prolactin and the reversibility of this untoward side effect were investigated. METHODS: 17 patients with various diagnoses received amisulpride (50-800 mg/day) or a combination of amisulpride plus other medication as needed. Plasma prolactin was determined 26.7+/-9.4 days (range: 13-50 days) after initiation of treatment and in 3 cases after a much longer period, and 14-51 days following its withdrawal. RESULTS: All patients on amisulpride had hyperprolactinemia (mean+/-S.D. prolactin levels: 62.5+/-33.0 ng/ml) with females exhibiting considerably higher prolactin levels than males. Following amisulpride discontinuation prolactin levels were significantly (p<000) reduced (mean+/-S.D. prolactin levels: 12.3+/-6.7 ng/ml). No significant correlation was detected between prolactin levels and either amisulpride dosage or duration of administration. CONCLUSION: Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation.     

Effects of (−)-OSU6162 and ACR16 on motor activity in rats,indicating a unique mechanism of dopaminergic stabilization

Dopaminergic stabilizers can be defined as drugs that stimulate or inhibit dopaminergic signalling depending on the dopaminergic tone. (-)-OSU6162 and ACR16 appear to possess such a profile. They have been proposed to act as partial dopamine receptor agonists or as antagonists with preferential action on dopaminergic autoreceptors. Previous studies have shown either stimulation or inhibition of behaviour in response to (-)-OSU6162 and ACR16, which has been suggested to reflect their dual effects on dopaminergic signalling. The aims of the present work are to (1) examine the relation between behavioural response to these drugs and activity baseline, and (2) test the suggested mechanisms of action by means of close comparisons with the known partial D2-receptor agonists (-)-3-PPP and aripiprazole, and the D2 autoreceptor preferring antagonist amisulpride with respect to effects on behaviour. From the results of these experiments it can be concluded that: (1) The direction of the response to (-)-OSU6162 and ACR16 is dependent on activity baseline, which in turn, under physiological conditions, is determined primarily by test arena size of and degree of habituation to the environment. (2) The effects of (-)-OSU6162 and ACR16 cannot be explained on the basis of either partial dopamine receptor agonism or preferential dopamine autoreceptor antagonism. Nevertheless, the current data suggest at least two different D2-receptor-associated targets which mediate opposite effects on activity. This result fits in with a mechanism proposed from a recent in vitro study, according to which (-)-OSU6162 has a dual action on dopamine D2 receptors, (a) an allosteric effect causing an enhanced response to dopamine, and (b) the previously proposed orthosteric effect antagonizing the action of dopamine.     

氨磺必利与奥氮平治疗精神分裂症的随机对照研究

目的 比较氨磺必利与奥氮平治疗精神分裂症的疗效与安全性.方法 将80例精神分裂症患者,随机分为氨磺必利组和奥氮平组,各40例,疗程8周.采用阳性与阴性症状量表(PANSS)、临床疗效总评量表(CG1)及治疗中出现的症状量表(TESS)分别评定疗效和不良反应.结果 经过8周治疗,氨磺必利组和奥氮平组显效率分别为65.8％和71.8％,两组疗效差异无统计学意义(P＞0.05).治疗后第8周末氨磺必利组阴性症状分较奥氮平组减少更显著(P＜0.05).安全性方面,氨磺必利组、奥氮平组不良反应总发生率分别为44.7％(17/38)和53.8％(21/39),差异无统计学意义(P＞0.05).氨磺必利组泌乳或月经紊乱发生率高于奥氯平组(P＜0.05),奥氮平组便秘和体重增加发生率高于氨磺必利组(P＜0.05).其他不良反应发生率差异无统计学意义(P均＞0.05).结论 氨磺必利和奥氮平对精神分裂症的疗效相当,不良反应轻,值得临床应用.