Sex-related elevation in cortisol during chronic treatment with alprazolam associated with enhanced cognitive performance

Objective There is evidence of more widespread use and abuse of benzodiazepines (BZPs) among elderly women. However, factors underlying this observation are poorly understood but could be related to more intense withdrawal reactions, which are a major risk factor for continued BZP use. We previously reported elevations in interdose morning plasma cortisol levels in healthy elderly individuals after chronic treatment with alprazolam, possibly consistent with increased hypothalamic–pituitary–adrenal (HPA) axis activity and drug withdrawal. In this study, we examined sex-related differences in this population. Method Twenty-five cognitively intact healthy elderly (13 women and 12 men) participated in a parallel, double-blind, placebo-controlled study that included a group that received acute and chronic (3 weeks) treatment with alprazolam (0.5 mg b.i.d.). Results Elderly women, but not men, experienced significant elevations in interdose morning plasma cortisol levels over 3 weeks of chronic treatment with alprazolam (0.5 mg b.i.d.) compared to placebo. In addition, higher morning plasma cortisol levels were significantly associated with better cognitive performance but not with higher plasma drug levels or greater degree of tolerance development to an acute alprazolam challenge. Conclusion Elderly females experienced a greater interdose activation of the HPA axis during treatment with therapeutic doses of alprazolam than men, which could be related to drug withdrawal.     

Alterations of GABAA receptor subunit mRNA levels associated with increases in punished responding induced by acute alprazolam administration: an in situ hybridization study

Changes in the mRNA encoding α1, α2, β2 and γ2 subunits of the GABA_A receptor associated with the anxiolytic effects of alprazolam were measured in 20 brain regions using in situ hybridization techniques. Compared to non-punished controls, punishment decreased α1 mRNA levels in two nuclei of the amygdala, the cerebral cortex, and the mediodorsal thalamic nucleus and decreased α2 mRNA levels in the hippocampus. Punishment increased β2 mRNA levels in ventroposterior thalamic nucleus and γ2 mRNA levels in the CA2 area of the hippocampus. All of these effects were reversed when alprazolam increased punished responding, while alprazolam alone had no effect on either non-punished responding or GABA_A receptor subunit regulation in these brain regions. Some brain regions that were unaffected by punishment were altered by alprazolam plus punishment. These results demonstrate that punishment and alprazolam can produce reciprocal changes in the mRNA levels for some subunits of the GABA_A receptor. These changes may alter GABAergic synaptic inhibition by altering the density of GABA_A receptors or their efficacy to bind drugs. They suggest that the underlying mechanisms by which drugs affect behavior can depend upon the conditions under which behavior is assessed.     

丁螺环酮治疗广泛性焦虑症的临床双盲对照研究

目的证实国产丁螺环酮治疗广泛性焦虑的疗效和安全性。方法用随机双盲对照治疗广泛性焦虑１５例,其中丁螺环酮９例,阿普唑仑对照组６例。结果显效率分别为７７．８％及６６．７％,二者差异无显著性（Ｐ＞０．０５）,用开放治疗２４例,显效率６２．５％。结论国产盐酸丁螺环酮抗焦虑作用肯定,副作用轻微     

Intravenous alprazolam challenge in normal subjects

Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the ₂ adrenore-ceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo. Alprazolam reduced ACTH and cortisol while increasing growth hormone. There was a transient reduction in plasma norepinephrine and only modest effects on cardiovascular parameters. Subjects became quite sedated after intravenous alprazolam. This pharmacodynamic profile resembles that previously reported for traditional benzodiazepines, although alprazolam may be a more potent stimulator of growth hormone release. Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonidine, alprazolam has relatively little effect on plasma catecholamine and cardiovascular parameters. This suggests that ₂ mechanisms do not play a primary role in alprazolam's mode of action. Since alprazolam infusion affects three different measures (ACTH/cortisol, growth hormone, and plasma norepinephrine) thought to be dysregulated in depression, challenge with intravenous alprazolam may prove to be a useful probe in affective disorders.     

阿普唑仑治疗肠易激综合征的临床疗效观察

目的观察阿普唑仑治疗肠易激综合征的临床疗效。方法将90例肠易激综合征患者随机分为观察组与对照组,每组各45例。对照组给予常规药物进行治疗,观察组在此基础上,加用阿普唑仑,治疗周期均为4周,治疗结束后评价治疗效果。结果观察组临床总有效率为86.67%,对照组临床总有效率为57.78%,两组间疗效差异显著,具有统计学意义(P<0.05)。结论阿普唑仑治疗肠易激综合征的临床疗效确切,值得推广使用。     

Cognitive, psychomotor and actual driving performance in healthy volunteers after immediate and extended release formulations of alprazolam 1 mg

Rationale Alprazolam extended-release (XR) is approved for the treatment of panic disorder. This sustained formulation is absorbed in a delayed manner and is therefore expected to produce fewer and less severe side effects than its immediate release equivalent (alprazolam IR). The effect of alprazolam XR on potentially dangerous daily activities, such as driving a car, is expected to be less as compared to alprazolam IR. Objectives The present study was designed to compare the effects of alprazolam XR (1 mg) and alprazolam IR (1 mg) on actual driving ability and cognitive function. Method Eighteen healthy volunteers (aged 20–45 years) participated in a double-blind, placebo-controlled, three-way crossover study. At 4 h post-dose, subjects performed a standardized driving test on a primary highway in normal traffic. Cognitive and psychomotor tests were assessed 1, 2.5, and 5.5 h post-dose. Memory functioning was measured only 1 h after administration. Results Both formulations severely impaired driving performance between 4 and 5 h after administration. The magnitude of impairment in the driving test observed with alprazolam XR was about half that observed with alprazolam IR. Laboratory test results were in line with the driving data. Conclusions The acute impairing effects of alprazolam XR 1 mg on driving and psychomotor functions were generally less, as compared to its immediate-release equivalent, but still of sufficient magnitude to increase the risk of becoming involved in traffic accidents.     

西酞普兰与阿普唑仑治疗广泛性焦虑障碍对照研究

目的 探讨西酞普兰(喜太乐)治疗广泛性焦虑障碍的临床疗效.方法 将64例广泛性焦虑障碍患者分成2组,每组32例.研究组口服西酞普兰治疗,对照组口服阿普唑仑治疗,观察4周,于治疗前及治疗2、4周末采用救密顿焦虑量表(HAMA)评定临床疗效,于治疗4周后用TESS评定不良反应.结果 治疗结束时2组HAMA评分均较治疗前显著下降(P＜0.01),2组间比较差异无统计学意义(P＞0.05).治疗4周后研究组总有效率为75.00％,对照组总有效率为78.12％,2组比较无统计学意义(P＞0.05);治疗4周后研究组较对照组不良反应少于对照组(P＜0.05).结论 西酞普兰治疗广泛性焦虑障碍疗效显著,与阿普唑仑相当,且不良反应较阿普唑仑少,可作为治疗广泛性焦虑障碍的一线用药.     

阿普唑仑加氟哌噻吨美利曲辛治疗AECOPD并焦虑的疗效观察

目的:观察阿普唑仑加氟哌噻吨美利曲辛治疗AECOPD并焦虑的临床疗效。方法:将86例住院治疗慢性阻塞性肺疾病急性加重期并焦虑患者随机分为治疗组和对照组各43例。两组患者均给予常规治疗,包括氧疗、抗感染、祛痰、平喘、静脉推注甲基强的松龙等。对照组为常规治疗。治疗组在常规治疗基础上加用口服阿普唑仑0.4mg,1次/睡前,氟哌噻吨美利曲辛10.5 mg口服,1次/d。两组患者均连续治疗14d。结果:两组患者治疗后FVC、FEV1及FEV1/FVC与治疗前比较,均明显改善,治疗前后比较差异有统计学意义(P<0.05,或P<0.01);治疗后治疗组患者的FVC、FEV1及FEV1/FVC均明显优于对照组,差异有统计学意义(P<0.05)。治疗后治疗组患者的HAMA和HAMD均明显优于对照组,差异有统计学意义(P<0.05)。结论:通过用抗焦虑抑郁药物阿普唑仑加氟哌噻吨美利曲辛对痰量不多、不粘稠、易咳出且二氧化碳无高的AECOPD患者干预后,能改善焦虑抑郁状态,控制病情,提高临床疗效。     

枣连安神散配合阿普唑仑治疗肌萎缩侧索硬化症伴焦虑60例

目的 观察枣连安神散配合阿普唑仑治疗肌萎缩侧索硬化症伴焦虑的临床疗效。方法 将120例患者随机分为治疗组和对照组,每组60例。两组均予肌萎缩侧索硬化症常规治疗措施及阿普唑仑,治疗组同时加服枣连安神散;两组疗程均为4周,观察焦虑临床疗效及汉密尔顿焦虑量表（HAMA）、焦虑自评量表（SAS）评分变化情况。结果 治疗组、对照组总有效率分别为91．7％和83．3％;组间焦虑临床疗效比较,差异有统计学意义（P〈0．05）。两组治疗前后组内比较,HAMA和SAS积分差异均有统计学意义（P〈0．05）;组间治疗后比较,HAMA和SAS积分差异均有统计学意义（P〈0．05）。结论 枣连安神散配合阿普唑仑是肌萎缩侧索硬化症伴焦虑的有效治疗方法。