草酸艾司西酞普兰联合氨磺必利治疗抑郁症的效果和安全性研究

目的探讨氨磺必利联合草酸艾司西酞普兰治疗抑郁症的有效性和安全性。方法采用随机数字表法将符合《国际疾病分类(第10版)》(ICD-10)抑郁症诊断标准的78例抑郁症患者分为草酸艾司西酞普兰组(对照组,n=40)和草酸艾司西酞普兰联合氨磺必利组(研究组,n=38),疗程8周。于治疗前和治疗后第2、4、6、8周末采用汉密尔顿抑郁量表17项版(HAMD-17)评定疗效,采用副反应量表(TESS)评定安全性和不良反应。结果治疗2周后,两组HAMD-17总评分比较差异有统计学意义(P0.01)。治疗4周后,研究组HAMD-17焦虑躯体化因子评分、体重因子评分、阻滞因子评分及总评分均较对照组低(P0.05或0.01)。两组总有效率差异有统计学意义(χ2=2.734,P0.01)。研究组与对照组口干、恶心、呕吐及便秘的发生率差异有统计学意义(P0.01)。结论在抑郁症的临床治疗过程中,相对于单用草酸艾司西酞普兰,联合用药可能会更有效地改善躯体症状,减轻早期消化道不良反应,加快起效时间。     

氨磺必利与利培酮治疗精神分裂症的疗效及不良反应的比较研究

目的：比较和研究氨磺必利与利培酮治疗精神分裂症的临床疗效和不良反应。方法：将118例精神分裂症患者随机分为研究组和对照组,研究组（n=59）给予氨磺必利,起始剂量0．2evd,每日2次;对照组（n=59）给予利培酮,起始剂量1mevd,每日1次。1周内氨磺必利加至0．9～1．2eva,利培酮加至3～6mevd,然后根据病情需要及不良反应情况进行调整。治疗时间为8周,采用阳性与阴性症状量表（PANSS）和副反应量表（TESS）评定其疗效和不良反应。结果：研究组总有效率为88．14％,对照组总有效率为84．75％,两组有效率相比较,差异没有显著性（≯=0．289,P=0．600）,PANSS量表中阳性症状评分,研究组（13．49±1．60）与对照组（13．65±1．78）相比较无明显差异（P〉0．05）;但阴性症状评分中研究组为（12．69±1．86）,明显优于对照组（17．99±1．81）（P〈0．05）,副反应量表TESS中研究组治疗后行为表现、化验、神经系统、自主神经系统、心血管系统及总评A与对照组相应指标相比较,差异有统计学意义（P〈0．05）。研究组的体重增加显著少于对照组（P〈0．05）。结论：氨磺必利治疗精神分裂症总体疗效明显优于利培酮,且体重增加显著减少。     

氨磺必利治疗精神分裂症40例临床疗效初探

目的探讨氨磺必利治疗精神分裂症患者的临床疗效。方法选择符合条件的精神分裂症患者40例,阳性亚型组以≥400mg/d为起始剂量,阴性亚型组以100～300mg/d为起始剂量的氨磺必利治疗10周,疗效评定采用阳性与阴性量表（PANSS）。结果治疗结束时,痊愈5.1%,显效69.2%,有效25.6%,PANSS量表总分及分量表分与治疗前比较均有显著性差异。结论氨磺必利对精神分裂症的阳性及阴性症状均有疗效,且以较低剂量即能明显改善阴性症状为突出特点。     

Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia

Amisulpride is a clinically effective antipsychotic drug in a broad dose range with low propensity for extrapyramidal symptoms (EPS). Daily doses and plasma levels of amisulpride were analyzed within a large-scale therapeutic drug monitoring (TDM) survey to find plasma level ranges for optimized treatment under naturalistic conditions. Data of 378 schizophrenic patients treated with amisulpride (100-1550 mg) were included (40% female). Amisulpride plasma levels were analyzed at steady state; assessment comprised improvement (CGI-I) and side-effects, particularly EPS. For detection of cut-off values regarding non-response or EPS, receiver operating characteristics (ROC) curves were applied and the area under the ROC curve (AUC) was calculated. Amisulpride daily doses (594+/-262 mg) and plasma levels (315+/-277 ng/ml) were significantly correlated (r=0.53; P<0.0001). Patients with non-response to amisulpride (8.9%) had significantly (P<0.05) lower plasma levels (248+/-291 ng/ml) than patients with at least moderate improvement (316+/-253 ng/ml) despite comparable amisulpride doses (628+/-253 vs. 590+/-263 mg). Patients with EPS (14.6%) had significantly (P<0.05) higher amisulpride plasma levels (377+/-290 ng/ml) than patients without EPS (305+/-274 ng/ml) despite similar doses in both groups (595+/-266 vs. 594+/-246 mg). ROC analyses revealed significant predictive properties of amisulpride plasma levels (P<0.05) for non-response (AUC=0.65+/-0.05) and EPS (AUC=0.62+/-0.05), respectively. Daily amisulpride doses did not significantly predict non-response or EPS. Optimal amisulpride plasma level values to avoid non-response and EPS were 100 or 320 ng/ml, respectively. Analysis of clinical utility revealed that blood levels must be analyzed in 7 patients until one patient benefits from the TDM procedure by avoiding non-response or EPS. Although our results were mainly explorative, TDM of amisulpride seems very useful for clinical decision making.     

舒肝解郁胶囊联合氨磺必利治疗肝脾不和型精神分裂症的临床疗效观察

目的　探讨舒肝解郁胶囊联合氨磺必利治疗肝脾不和型精神分裂症的临床疗效。方法　选取2019年3月至2021年3月在三门峡市康复医院确诊的85例肝脾不和型精神分裂症患者,简单随机将其分为观察组和对照组。将采用氨磺必利治疗的42例患者纳入对照组,将采用舒肝解郁胶囊联合氨磺必利治疗的43例患者纳入观察组,均持续治疗6周。观察组男23例,女20例,年龄（40.35±6.17）岁;对照组男18例,女24例,年龄（41.27±6.24）岁。评估观察组和对照组患者治疗后的临床疗效,比较两组患者治疗前后的中医症候积分及治疗期间的不良反应发生率。计量资料组间比较采用独立样本t检验,组内治疗前后比较采用配对t检验,计数资料采用χ²检验。结果　观察组治疗有效率为95.35%（41/43）,高于对照组80.95%（34/42）（P<0.05）。治疗6周后,观察组胁腹胀痛、食少纳呆及神疲懒言症候积分分别为（2.08±0.28）分、（1.96±0.37）分及（2.17±0.21）分,低于对照组的（2.23±0.22）分、（2.17±0.24）分及（2.32±0.27）分（均P<0.05）。观察组患者治疗期间不良反应发生率为13.95%（6/43）与对照组的9.52%（4/42）比较差异无统计学意义（P>0.05）。结论　舒肝解郁胶囊联合氨磺必利治疗可以明显提高肝脾不和型精神分裂症患者的临床疗效。     

Potentiation of prepulse inhibition of the startle reflex in rats: pharmacological evaluation of the procedure as a model for detecting antipsychotic activity

Prepulse inhibition (PPI) of the startle reflex – whereby presentation of a weak prepulse preceding a startling pulse diminishes the amplitude of the startle reflex – is disrupted by dopamine (DA) agonists; this disruption can be reversed by antipsychotics. There are also some indications in the literature that a few antipsychotics (most notably clozapine and haloperidol) may, on their own, have effects opposite to those of DA agonists, i.e. may enhance PPI. In order to explore these antipsychotic-induced potentiations of PPI more thoroughly, we assessed, in Sprague-Dawley rats, the effects of IP administration of various clinically effective antipsychotics in a PPI procedure with levels of PPI (ranging from 5 to about 40%) low enough to facilitate detection of PPI-potentiating effects of drugs. Both clozapine (5–20 mg/kg) and haloperidol (0.25–1 mg/kg) robustly and dose-dependently potentiated PPI. A similar effect was not seen with risperidone (0.1–1 mg/kg) or with the three substituted benzamides amisulpride (10–60 mg/kg), raclopride (0.1–3 mg/kg) and remoxipride (1–10 mg/kg). As risperidone is known to have prominent 5-HT₂ antagonistic activity, these results do not indicate a role for 5-HT₂ receptors in the clozapine and haloperidol PPI-enhancing effects. The absence of effects with the benzamides and with risperidone, at doses with known anti-dopaminergic activity, suggests that DA antagonist activity is not involved. The demonstration that prazosin (3–20 mg/kg), a non-antipsychotic with α₁ adrenoceptor antagonistic properties, dose-dependently potentiated PPI indicates that α₁ receptors might mediate the clozapine and haloperidol PPI-enhancing activity. Additionally, the finding that diazepam (1–10 mg/kg) did not enhance, but on the contrary reduced PPI, argues against a sedation- or general depressant-mediated effect of clozapine, haloperidol and prazosin. The negative results with four clinically active antipsychotics (risperidone and the benzamides), and the positive result with the non-antipsychotic prazosin, indicate that this PPI-enhancing procedure has poor predictive validity as a screening tool for potential antipsychotics. Received: 14 November 1996/Final version: 6 February 1997     

Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI

BACKGROUND: Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D(2/3) blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. METHODS: Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. RESULTS: Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. CONCLUSIONS: Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.     

氨磺必利与齐拉西酮对精神分裂症的随机、开放性对照研究

目的：比较氨磺必利与齐拉西酮在治疗精神分裂症的疗效和不良反应。方法：将78例符合标准的成年精神分裂症患者随机分为两组,氨磺必利组（n=38）口服氨磺必利治疗;齐拉西酮组（n=40）口服齐拉西酮治疗。观察8周。于治疗前以及治疗后第2周、第4周、第8周末,用PANSS量表评定临床效果,用不良反应量表（TESS）评定不良反应。结果：治疗结束时,两组PANSS评分较入组时均有显著降低（P〈0.05）,两组组间比较,无明显差异（P〉0.05）,两者不良反应较少两组间比较无明显差异（P〉0.05）。结论：氨磺必利与齐拉西酮对精神分裂症的治疗安全有效,氨磺必利对情感症状较齐拉西酮有更好的治疗效果。     

氨磺必利与利培酮治疗精神分裂症患者的对照研究

目的：比较氨磺必利与利培酮治疗精神分裂症患者疗效与不良反应。方法：140例符合中国精神障碍分类与诊断标准第3版精神分裂症诊断标准的患者随机分为两组,每组70例：分别给予氨磺必利与利培酮治疗8周,采用阳性与阴性量表（PANss）评定疗效,治疗中出现的症状量表（TESS）评定不良反应。结果：治疗8周后氨磺必利组治愈率34．3％,有效率77．1％,利培酮治愈率32．9％,有效率32．9％,两组疗效比较无显著性差异（P〉O．05）;氨磺必利组不良反应发生率41．43％,利培酮组发生率为45．7％,两组比较无显著性差异（P〉0．05）。结论：氨磺必利与利培酮治疗精神分裂症的疗效和不良反应相似,需根据患者具体情况选择合适的药物。     

文拉法辛联合氨磺必利治疗重度抑郁症的疗效及安全性研究

目的探究文拉法辛联合氨磺必利治疗重度抑郁症患者的临床效果与安全性。方法选取2018年11月至2019年11月本院收治的重度抑郁症患者50例作为研究对象,采用随机列表法分为两组,各25例。对照组采用文拉法辛治疗,研究组在对照组基础上采用氨磺必利治疗,比较两组临床治疗效果与安全性。结果研究组治疗有效率高于对照组,差异有统计学意义(P<0.05)。治疗后,两组患者抑郁自评量表评分(self-rating depression scale,SDS)均有所降低,且研究组低于对照组,差异有统计学意义(P<0.05)。治疗后,两组患者白细胞介素-18(IL-18)水平均降低,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组不良反应发生率低于对照组,差异有统计学意义(P<0.05)。结论采用文拉法辛联合氨磺必利治疗重度抑郁症患者,可有效提升患者治疗效果与安全性,对于患者具有积极意义,值得推广应用。