丁螺环酮和阿普唑仑治疗广泛性焦虑研究

目的：比较国产丁螺环酮和阿普唑仑治疗广泛性焦虑的疗效和不良反应。方法：对78例广泛性焦虑按照就医顺序分为两组，分别服用丁螺环酮(38例)和阿普唑仑(40例)。疗程6周。于治疗前及治疗第1、2、4、6周末进行汉密尔顿焦虑量表(HAMA)及副反应量表(TESS)评定疗效和不良反应。结果：丁螺环酮和阿普唑仑的疗效相仿，丁螺环酮的不良反应少且轻微，无过度镇静和肌肉松弛作用，不产生药物依赖。结论：丁螺环酮是治疗广泛性焦虑较为理想的药物。     

Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo

This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week, placebo-controlled trial of alprazolam and imipramine (n = 126). Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment. Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4. At endpoint, the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance. This relationship was not evident for completers, suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced.     

国产曲唑酮治疗焦虑症的疗效分析

目的观察国产曲唑嗣对焦虑症的疗效。方法选择我院符合CCMD-3诊断标准的焦虑症病例90例（男27例，女60例，脱落3倒），随机分3组，每组30例，分别用国产曲唑酮100～200mg／d，po，阿普唑仑1．6mg／d，po，劳拉西泮2mg／d，po，共观察4周。结果国产曲唑酮组的总有效率基本与其他2组相仿（P〉0．05），仅第4周优于阿普唑仑组（P〈0．05）。HAMA减分率与第1周阿普唑仑组及各周劳拉西泮组差别元显著意义（P〉0．05），但与第2周、第4周阿普唑仑组比较差别有显著和非常显著意义（P〈0．05或P〈0．01）。药物副作用少而轻，以胃肠道不适和困倦感为主，仅3例分别出现头痛、头晕伴烦躁不安、焦虑症状加重而退出实验。结论国产曲唑酮是有效的抗焦虑药物，且副作用小。     

Depletion of brain norepinephrine: differential influence on anxiolyic treatment effects

Rationale: Previous studies have demonstrated that anxiolytic-like anticonflict effects can be produced by either (1) acute administration of traditional anti-anxiety compounds (benzodiazepines or barbiturates) or (2) chronic administration of tricyclic (TCA) or monoamine oxidase inhibitor (MAOI) antidepressants. Objective: The present study determined the effects of noradrenergic neuronal depletion on these distinct anticonflict treatments. Methods: After 3 weeks of training in a repeated measures drink suppression conflict paradigm, water-restricted rats consumed 11–14 ml water/session (unpunished responding) and accepted 25–40 shocks/session (punished responding) during control (i.e., non-drug) 10-min test sessions. The noradrenergic neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride; 65 mg/kg, IP] or its vehicle (saline; 1 ml/kg) was administered after 3 weeks of conflict testing. Conflict behavior was then evaluated for 8 weeks post-treatment. In separate groups of DSP4- and vehicle-pretreated subjects, the effects of acute administration (10-min pretreatment) of phenobarbital (5–40 mg/kg) or alprazolam (0.3–2.5 mg/kg) were determined. In a third experiment, the effects of chronic treatment with the TCA desipramine (DMI; 5 mg/kg, twice daily for 8 weeks) or the non-selective MAOI phenelzine (4.0 mg/kg, twice daily for 8 weeks) on conflict behavior were determined in additional groups of DSP4- or vehicle-pretreated subjects. Results: DSP4 treatment produced a modest yet statistically significant decrease in punished responding (i.e., anxiogenic-like effect) relative to vehicle controls. DSP4 pretreatment did not alter the anticonflict effects of acute alprazolam or phenobarbital treatment. In contrast, DSP4 treatment completely abolished the anticonflict effects produced by chronic DMI or chronic phenelzine treatment. Conclusions: Thus, noradrenergic neuronal integrity appears to be required for the anxiolytic-like effects of chronic antidepressant treatment, but not for the anxiolytic-like effects of acute treatment with barbiturates and benzodiazepines. Received: 6 August 1998/Final version: 16 October 1998     

Influence of ethanol on the metabolism of alprazolam.

Background: Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown.

Research design and methods: The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. In silico molecular docking was applied to analyze the change in the CYP3A4–alprazolam-binding conformation when ethanol was coadministered with alprazolam.

Results: Compared with alprazolam administered alone (2 mg/kg), the C_max of alprazolam increased when ethanol was simultaneously administered at 3 g/kg. The concentrations of alprazolam significantly increased by 39%, 17%, 105%, and 642% at 5, 10, 30, and 120 min intervals in the brain when coadministered with ethanol, respectively. Molecular docking results suggested that the conformation of CYP3A4 with alprazolam changed when ethanol was bound to the SER119 residue, which seems critical in the process of CYP3A4–alprazolam binding.

Conclusions: Ethanol might increase the toxicity of alprazolam by inhibiting the activity of CYP3A4, although other pharmacokinetic processes may be affected. Ethanol could change the conformation of CYP3A4 and affect alprazolam binding.     

万拉法新与丁螺环酮和阿普唑仑治疗焦虑症的对照研究

目的:比较万拉法新与丁螺环酮和阿普唑仑治疗焦虑症的疗效和副反应。方法:将符合CCMD-3焦虑症诊断标准的门诊病人59例,随机分为3组,分别采用万拉法新、丁螺环酮和阿普唑仑治疗,疗程6周。于疗前及疗后1、2、4、6周末分别以HAMD-A、CGI-1、TESS评定。结果:万拉法新其疗效与丁螺环酮和阿普唑仑相近,起效虽稍慢阿普唑仑,但中长期疗效更持久更稳定,没有严重副反应和成瘾性。结论:万拉法新是安全有效的抗焦虑药。     

米氮平治疗失眠症的临床疗效分析

目的 探究米氮平治疗失眠症的疗效.方法 选取我院2012年1月-2013年1月治疗失眠症状患者66例.随机分为对照组与研究组,每组33例.对照组口服阿普唑仑.研究组在此基础上加用米氮平,疗程均为4周.疗效采用匹兹堡睡眠质量指数（PSQI）及夜间睡眠与日间睡眠时间比值进行评定并采用副反应量表（TESS）判定不良反应.结果 研究组总有效率为72.72%高于对照组45.45%,两组比较差异有统计学意义（P＜0.05）.比较两组患者PSQI评分,研究组评分治疗后优于对照组,两组比较差异有统计学意义（P＜0.05）.4周后研究组TESS量表得分（4.04±0.88）分,对照组得分（3.89±1.07）分,两组比较差异无统计学意义（P＞0.05）.两组患者不良反应发生率比较差异无统计学意义（P＞0.05）.结论 阿普唑仑与米氮平联合使用,有效快速控制失眠症状,同时不良反应亦不明显大于单药使用,适合临床推广.     

阿普唑仑和氟西汀治疗顽固性功能性胃肠病的疗效比较

目的比较阿普唑仑和氟西汀治疗功能性胃肠病(FGID)的疗效,并探讨抗焦虑药和抗抑郁药在治疗FGID中的作用和地位。方法在常规疗法基础上,分别联用阿普唑仑和氟西汀治疗323例顽固性功能性消化不良(FD)和肠易激综合征(IBS)8周,并与单用常规疗法对照,评测其治疗前后消化道症状和焦虑、抑郁自评量表积分变化。结果阿普唑仑组和氟西汀组的消化道症状有效率分别为50. 9 %和55. 6 % (P=0. 552),均显著高于常规疗法的22. 4 % (P<0. 001);便秘主导型IBS消化道症状有效率三组差异无统计学意义(P=0. 990);阿普唑仑组和氟西汀组FD和腹泻主导型IBS原有精神异常患者和无精神异常患者的消化道症状有效率分别为58. 3 %和50. 8 %,差异无统计学意义(P=0. 328);阿普唑仑组和氟西汀组治疗前后焦虑自评量表(SAS)总分差值比较无统计学意义(P=0. 067),抑郁自评量表(SDS)总分差值比较则氟西汀组优于阿普唑仑组(P<0. 001)。结论阿普唑仑和氟西汀均能改善FGID的消化道症状,疗效与症状类别有关,与目前是否存在精神异常无关。     

万拉法新与阿普唑仑治疗广泛性焦虑症对照研究

目的：验证万拉法新治疗广泛性焦虑的疗效及不良反应。方法：68例广泛性焦虑症按就医顺序分为两组，分别用万拉法新及阿普唑仑进行治疗，疗程6周，于治疗前及治疗后第1、2、4、6周末进行汉密顿焦虑量表（HAMA）、焦虑自评量表（SAs）、副反应量表（TESS）评定疗效及不良反应。结果：万拉法新和阿普唑仑两药疗效相仿，万拉法新不良反应少而轻微。结论：万拉法新是治疗广泛性焦虑症较为理想的药物。     

加味酸枣仁合剂治疗广泛性焦虑症对照研究

目的:观察加味酸枣仁合剂治疗广泛性焦虑症的临床疗效和安全性。方法:将195例广泛性焦虑症患者随机分为研究组(加味酸枣仁合剂治疗)98例和对照组(阿普唑仑治疗)97例,疗程6周,于疗前、及治疗后第1、2、4、6周末采用Hamil- ton焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应。结果:两组疗效相似,加味酸枣仁合剂组总有效率为65．3％;阿普唑仑组总有效率69．1％,两组无统计学差异;加味酸枣仁合剂的不良反应以胃肠道症状为主,阿普唑仑的不良反应以嗜睡为主。结论:加味酸枣仁合剂用于治疗广泛性焦虑症安全有效。