西酞普兰与阿普唑仑治疗广泛性焦虑症对照研究

目的：探讨西酞普兰治疗广泛性焦虑症的临床疗效。方法：将66例广泛性焦虑症患者随机分为两组,西酞普兰组34例,阿普唑仑组32例。西酞普兰组治疗剂量40～60 mg/d,阿普唑仑组为2.4～3.6 mg/d,观察时间均为6周。治疗前与治疗第1、2、4、6周末采用HAMA、SAS、TESS评定临床疗效和副反应。结果：两组疗效相当,差异无统计学意义（P〉0.05）;阿普唑仑组起效时间快,但远期疗效差于西酞普兰组;西酞普兰组副反应明显少于阿普唑仑组（P〈0.05）。结论：西酞普兰治疗广泛性焦虑疗效肯定,依从性好。     

中医辨证论治结合心理疗法治疗失眠45例

目的:观察中医辩证论治结合心理疗法治疗失眠的临床疗效.方法:将90例失眠症患者随机分为治疗组和对照组各45例,治疗组予中医辨证论治结合心理疗法治疗;对照纽予西药阿普唑仑治疗,疗程均为1月.比较两组疗效且用AIS评测治疗后第1、2、3、4周睡眠质量.结果:①治疗1周后两组AIS评分较治疗前明显下降(P<0.05);治疗2...     

丁螺环酮治疗老年焦虑症临床对照研究

目的探讨丁螺环酮治疗老年焦虑症的疗效及安全性。方法68例老年焦虑症患者随机分为两组,分别给予丁螺环酮和阿普唑仑治疗,疗程6周。使用汉密尔顿焦虑量表（HAMA）评定疗效,利用治疗中出现的症状量表（TESS）和实验室检查评价不良反应。结果丁螺环酮与阿普唑仑疗效相当,不良反应丁螺环酮较阿普唑仑少而轻。结论丁螺环酮治疗老年焦虑症疗效好,不良反应少,值得临床推广。     

Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice

Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72 h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25 mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.     

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide

Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for four weeks, each separated by a two-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol. Received: 28 August 2000 / Accepted in revised form: 12 December 2000     

氟西汀与阿普唑仑治疗慢性失眠症的对照研究

目的探索氟西汀对慢性失眠症的治疗是否有效,同时比较氟西汀与阿普仑对慢性失眠症的治疗效果。方法将84例符合慢性失眠症诊断标准的患者随机分为氟西汀治疗组和阿普唑仑治疗组。采用匹兹堡睡眠质量指数（PSQI）及睡眠日记对睡眠质量进行评定。结果治疗的第1天、第8天,阿普唑仑组患者睡眠状况显著改善,而氟西汀组则无明显变化;治疗的第15天,氟西汀组患者睡眠状况显著改善,睡眠各项指标与治疗前及阿普唑仑组相比,差异具有统计学意义,而阿普唑仑组患者的睡眠状况又恢复到治疗前水平;治疗结束时及治疗结束后3个月,氟西汀组患者的睡眠状况依然好于治疗前及阿普唑仑组,差异具有统计学意义。结论氟西汀可以有效治疗慢性失眠症,远期效果好于阿普唑仑。     

Effect of the pregnane-related GABA-active steroid alphaxalone on mice performance in the staircase test

We evaluated the modulatory effect of the GABA-active neurosteroid alphaxalone on the staircase test behavior of mice. Results were compared with the benzodiazepine alprazolam, the GABA_A agonist muscimol and the peripheral steroids corticosterone and progesterone. Alphaxalone and alprazolam reduced rearing activity in a dose-dependent manner, at doses that did not suppress climbing. The rearing-suppression effect of alprazolam, but not of alphaxalone, was blocked by the benzodiazepine antagonist flumazenil. No such dissociation between the effect on rearing and climbing was obtained with muscimol, and both activities were suppressed, in a flumazenil-insensitive pattern, at high doses. Corticosterone and progesterone did not affect the behavior of the mice. The lack of sensitivity of both phenobarbital and alphaxalone to flumazenil indicates that neither agents act via the benzodiazepine recognition site at the GABA_A receptor complex.     

Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder

The efficacy and safety of alprazolam and buspirone for treating generalized anxiety disorder (GAD) were compared in a 6-week, double-blind, randomized, placebo-controlled study of 94 outpatients. Mean daily doses at the end of the study were 1.9 mg alprazolam and 18.7 mg buspirone. As judged by the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Physician's Global Improvement Scale, and other efficacy scales, alprazolam and buspirone were similar in efficacy, but more effective than placebo, for treating anxiety and depression symptoms in these patients. Clinically important differences were noted between drugs in the onset of effect, with alprazolam producing rapid and sustained improvement within the first week of treatment and buspirone producing more gradual, continuous improvement throughout the study. Significantly more buspirone-treated than alprazolam-treated patients failed to complete the study, primarily because of side effects or inefficacy. No clinically important differences were noted between alprazolam and buspirone in side effects, vital signs, or laboratory test results. Alprazolam-treated patients most frequently reported central nervous system-related side effects (drowsiness and sedation), while buspirone-treated patients most frequently reported gastrointestinal system-related side effects (appetite disturbances and abdominal complaints).     

The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: Psychopharmacological validation

Several lines of evidence have established that performance during the initial steps of acquisition on a shuttle-box avoidance task is an anxiety-mediated behavior (i.e., the differences between strains selectivity bred for emotionality; the effects of postnatal handling; the course of the corticosterone response and behavioral measures of fear during acquisition). The present study was carried out to add pharmacological evidence to that view by testing the action of anxiogenic and anxiolytic drugs. Single 40-trial sessions with mild shocks (0.4 mA-0.6 mA) were used. In the first experiments the action of sodium pentobarbital (1.25, 2.5 and 5 mg/kg) and three benzodiazepines (diazepam, 2 and 4 mg/kg; alprazolam, 1, 1.25 and 1.5 mg/kg and adinazolam, 1, 2, 4 and 6 mg/kg) were tested. The last two experiments tested a possible proanxiety action of Ro 15-4513 (2, 5 and 10 mg/kg) and FG 7142 (5, 10 and 15 mg/kg), two partial inverse agonists of benzodiazepine receptors, which previous data had suggested to be anxiogenic. The results showed that the measure of acquisition of a two-way active avoidance is a sensitive mean for detecting either anxiolytic or anxiogenic effects of drugs, independently of their effects on locomotor activity, thus suggesting that such test could be a valid model of anxiety in animals.     

Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects

The relationships between alprazolam and metabolite concentrations and CNS effects were determined in a double-blind placebo controlled four-way crossover trial in 16 normal male volunteers. Active drug treatments consisted of 4-day regimens of 4 mg alprazolam PO daily as 2 mg bid., 1 mg qid, and 0.25 mg each hour. On days 1 and 4, the kinetics, sedative and psychomotor effects were evaluated. Plasma concentrations of the 4- and α-hydroxy metabolites of alprazolam were less than 10% of unchanged alprazolam levels on both days. Accumulation of these metabolites and alprazolam was dependent on alprazolam half-life (11.6 h). Acute and chronic tolerance to the sedative and psychomotor effects was observed with all active drug treatments. All alprazolam treatments resulted in significantly greater sedation than placebo on days 1 and 4. However, on day 4, sedation was 16–36% less than observed on day 1, despite plasma concentrations 1.4–2.76 times the day 1 concentrations. Sedation from alprazolam was reduced in each successive study phase, suggesting a tolerance which was sustained during the 10-day washout between phases. By day 4, psychomotor performance was not different from placebo, indicating more complete development of tolerance than occurred for the sedative effect. Sedation and psychomotor impairment on day 1 were greatest with 2 mg alprazolam bid. During the initiation of therapy, the patient will likely experience less sedation and psychomotor impairment with smaller, more frequent doses. Since tolerance develops to these effects, the advantage of more frequent dosing regimen dissipates by the 4th day.