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.     

A case of local anesthetic toxicity that wasn’t: lipid rescue from self-administered benzodiazepine overdose in labor

A 32-year-old G2P1 woman presented for induction of labor at term. Her past medical history included polysubstance use disorder and methadone maintenance, scant prenatal care, morbid obesity, and intimate partner violence. Her induction was progressing smoothly until the acute onset of altered mental status near to the time of delivery, several minutes after a clinician-administered epidural local anesthetic bolus for significant pain. Given concern about local anesthetic systemic toxicity, lipid emulsion was administered and resulted in an immediate and drastic clinical response. The epidural infusion bag and pump system were evaluated and found to be correct and there was no clinical suspicion of an intravascular epidural catheter. The woman remained stable and was transferred to the postpartum unit, where she experienced a similar episode of altered mental status approximately 12 h postpartum. This episode self-resolved and she was managed conservatively. Shortly after this event, it was discovered that the patient had been self-administering benzodiazepines throughout the course of her labor, in addition to her hospital staff-administered medications. Presumably, her intrapartum altered mental status was a result of self-administered benzodiazepine that was then “rescued” with lipid emulsion. This case illustrates the potential for lipid emulsion as a reversal agent for medications other than local anesthetics.     

A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine

We have assesed the pharmacokinetic and pharmacodynamic interaction between fluvoxamine, a serotonin reuptake inhibitor, and alprazolam, a triazolobenzodiazepine.Healthy men took fluvoxamine maleate daily for 10 days (50 mg on days 1–3, 100 mg on days 4–10) (n=20), 1 mg of alprazolam four times daily for four days (days 7–10 of the study period) (n=20), or a combination of the two (n=20), according to a parallel study design. Alprazolam and fluvoxamine concentrations were measured in serial plasma samples by HPLC and gas chromatography respectively, and psychomotor performance and memory were assessed on days 1, 7, and 10.Fluvoxamine increased plasma alprazolam concentrations by 100%. The mean apparent half-life of alprazolam was increased from 20 h to 34 h after fluvoxamine co-administration.The increased plasma concentrations of alprazolam resulted in significantly greater reductions in psychomotor performance evident on day 10. Mean fluvoxamine plasma concentrations were about 25% lower in those who took the combination than in those who took only fluvoxamine; this was more likely due to heterogeneity between the treatment groups than to an effect of alprazolam.The dosage of alprazolam should be reduced during co-administration with fluvoxamine.     

Comparative pharmacokinetics and pharmacodynamics of lorazepam,alprazolam and diazepam

The contribution of differential absorption-distribution pharmacokinetics to drug activity can be partially determined by comparing simultaneous estimates of drug serum level with pharmacodynamic effects. In the present paper we have contrasted the effects of clinically equipotent doses of lorazepam, alprazolam, and diazepam on the performance of tracking and digit symbol substitution tasks. Eight young males were tested for 12 h after ingesting the drug. The three benzodiazepines and placebo were administered to each subject according to a balanced double-blind Latin square design. A model is presented that describes the relationship between drug concentration and the degree of impairment across time after the final peak effect. Exponential rate constants were determined for each drug using a Marquardt nonlinear fit of the pooled data. Basically, the constants relate offset serum drug values to the impairment curves at a time when serum-brain equilibrium is assumed to have occurred. The values indicate markedly rapid acute tolerance for alprazolam and diazepam but relatively little acute tolerance for lorazepam. Whether these constants reflect adaptation or differential association-dissociation receptor rate constants cannot be determined, but they do highlight the need to consider receptor kinetics as an important factor in benzodiazepine pharmacodynamics.     

西酞普兰与阿普唑仑治疗广泛性焦虑症的对照研究

目的探讨西酞普兰治疗广泛性焦虑症的临床疗效及安全性。方法将52例广泛性焦虑症患者随机分配至西酞普兰组及阿普唑仑组各26例，西酞普兰治疗剂量为20-40mg／d，阿普唑仑为1．2-2．4mg／d，观察时间均为4周。疗效评定采用Hamilton焦虑量表(HAMA)及焦虑自评量表(SAS)。安全性评价应用TESS、实验室检查及查体。结果西酞普兰组显效率为69％，有效率为88％，阿普唑仑组显效率65％，有效率为85%；两者疗效相当；西酞普兰组不良反应较阿普唑仑组少且轻微，病人依从性好。结论西酞普兰是一种安全、有效的抗焦虑药。     

Double-Blind Study of Alprazolam, Diazepam, Clonidine, and Placebo in the Alcohol Withdrawal Syndrome: Preliminary Findings

Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the α₂-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam ( n = 6), the α₂-receptor agonist clonidine ( n = 7), the benzodiazepine alprazolam (that is also purported to have α₂-receptor agonist properties) ( n = 6), and placebo ( n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its α₂-receptor agonist properties.     

A comparative study of the psychological effects of DN-2327, a partial benzodiazepine agonist,and alprazolam

The effects of single oral doses of DN-2327 (DN, 2 mg or 3 mg), a newly developed partial benzodiazepine receptor agonist, and alprazolam (APZ, 0.8 mg), a full receptor agonist, on psychomotor function and short-term memory were assessed using three psychometric tests: letter cancellation, visual vigilance and Sternberg's memory scanning task. Twelve healthy male volunteers participated in this study. Randomized, double-blind, cross-over test sessions were conducted at 2-week intervals. Both 3 mg DN and 0.8 mg APZ increased the time to completion of the letter cancellation task at 3 h after administration, but neither had any effect on accuracy of response. In the visual vigilance task, which required relatively intense concentration and continuous attention, both the number of errors and reaction times to correct responses significantly increased from 1.5 to 3.5 h after administration of 3 mg DN and at 3.5 h after administration with 0.8 mg APZ. DN at 2 mg also significantly increased the number of errors from 1.5 to 3.5 h after administration, but it did not affect reaction times. In the memory scanning task, 3 mg DN, but not 2 mg DN or APZ, significantly increased overall reaction times at 2 h after administration. These performance deficits paralleled the time-course changes in serum concentrations of both drugs and appeared to be associated with the hypnotic-sedative effects of the drugs tested. These findings did not support those of previous preclinical studies of DN, indicating superiority of DN over conventional full benzodiazepine agonists/anxiolytics in terms of adverse behavioral consequences.     

Treatment of depressive outpatients with lorazepam,alprazolam, amytriptyline and placebo

This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline. While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups.     

万拉法新与阿普唑仑治疗广泛性焦虑临床对照研究

目的比较万拉法新与佳乐安定的抗焦虑效果和副作用。方法符合CCMD-3广泛性焦虑诊断标准的123例患者，随机分为研究组和对照组；用HAMA评定症状变化，用TESS评定副作用，疗程6周。结果治疗组显好率、有效率分别为76．9％、92．30％，对照组分别为72．41％、89．66％，两组总有效率接近。治疗组副反应恶心、头痛、口干、嗜睡等较多见。结论万拉法新治疗广泛性焦虑效果较好、副反应轻微。     

阿米替林并阿普唑仑按需治疗慢性失眠症效果

目的观察阿米替林与阿普唑仑联合按需治疗慢性失眠症的临床效果。方法慢性失眠症病人78例,随机分成对照组40例,治疗组38例,分别采取连续或按需口服阿米替林与阿普唑仑;采用匹兹堡睡眠指数（PSQI）和副反应量表（TESS）评价疗效和不良反应。结果持续治疗和按需治疗的疗效相近,治疗过程中无反跳现象及撤药反应。结论阿米替林与阿普唑仑联合按需治疗慢性失眠症安全有效,可减少阿普唑仑的日用量,降低阿普唑仑耐药性和副作用的发生。