创伤后应激障碍药物治疗进展

目的:综述近期国外药物治疗创伤后应激障碍(PTSD)的进展情况.方法:检索国外相关研究报道归纳综述.结果:多种药物对PTSD有效,苯二氮(艹卓)类药物(BZ)起效快,应激早期应用可预防PTSD的发生,但长期应用易导致依赖,停药出现戒断反应,并损害认知功能;选择性5-羟色胺再摄取抑制剂(SSRIs)在疗效和安全性方面被认为"最好",其他新型抗抑郁药和非BZ类抗焦虑药疗效较好,不良反应轻,是治疗PTSD较有前途的药物;三环类抗抑郁剂(TCAs)和单胺氧化酶抑制剂(MAOIs)疗效肯定,但不良反应较多.结论:不同种类药物对PTSD的作用机制不同,一种药物无效时可选用其他不同种类的药物,SSRIs抗抑郁药可作为一线用药,其他新型抗抑郁药和非BZ类抗焦虑药疗效较好,值得推广,TCAs和MAOIs应慎用.     

创伤后应激障碍药物治疗新进展及临床评价

目的:通过回顾药物治疗创伤后应激障碍(PTSD)的研究进展,以评价各类药物治疗PTSD的疗效和安全性.方法:通过查阅近期国内外相关文献进行评价.结果与结论:应激早期应用苯二氮()类药(BZ)可预防PTSD的发生,但长期应用易导致依赖,停药出现戒断症状,损害认知功能,三环类抗抑郁药和单胺氧化酶抑制剂疗效肯定,但不良反应较多,逐渐被安全有效的新型抗抑郁药特别是选择性5-羟色胺再摄取抑制剂所取代.近年来抗惊厥药和非典型抗精神病药治疗PTSD取得一定的疗效.     

社交焦虑障碍的药物治疗

社交焦虑障碍是常见的焦虑障碍之一.目前临床常用治疗药物主要有选择性5-羟色胺再摄取抑制剂(SSRI)、选择性5-羟色胺和去甲肾上腺素再摄取抑制剂(SSNRI)及苯二氮(艹卓)类药物等.本文综述药物治疗近况.     

失眠的治疗药物疗效与应用策略

治疗失眠的药物研究及失眠的治疗方法近年来取得很大的进展。失眠的治疗药物主要有苯二氮艹卓类药物和非苯二氮艹卓类药物（如吡唑嘧啶类、吡咯环酮类、咪唑吡啶类、GABA受体激动药及其再摄取抑制药等）以及其他有助于睡眠的药物（包括抗焦虑药物、抗抑郁药物、褪黑素及激素类药物）等;新型催眠药物的研制为失眠的治疗提供了新的选择。临床应根据失眠的不同形式和病因选择不同治疗药物;失眠的药物治疗应个体化,使用最低有效剂量、短期给药;对于慢性失眠,目前采用＂按需治疗＂方法正在取代持续使用镇静催眠药物。     

5-氯-2-甲氨基二苯酮的制备

由5-氯-2-氨基二苯酮(简称氨基酮)制成其N-单甲基物(Ⅰ)为生产二氮杂(艹卓)类安眠镇静药和抗焦虑药的重要中间体,也是制备非二氮杂(艹卓)类如甘氨酰芳胺(Glyanilides)类药物的重要原料。     

舒乐安定引起遗尿一例

舒乐安定(Surazepam;Estazolam)又名三唑氯安定,系苯并二氮杂(艹卓)类的新型抗焦虑药,其倦眠作用比安定(Diazepam)强5倍,临床应     

半个世纪的争议——苯二氮()类药物临床应用50年

上个世纪50年代,苯二氮(艹卓)类药物进入临床使用,由于此类药物高效、安全、耐受性良好,目前苯二氮(艹卓)类药物已成为抗焦虑和失眠领域应用最广泛的药物。根据统计,全球有超过5000万人服用苯二氮(艹卓)类药物。苯二氮(艹卓)类药物目前仍是失眠和抗焦虑的一线治疗药物。 然而,由于许多原因,苯二氮(艹卓)类药物只是用于短期的抗焦虑及失眠的治疗,这是因为人们担心长期使用     

扎来普隆的研究现状和应用前景

扎来普隆(zaleplon)是一种吡唑并嘧啶类化合物,属于新型非苯二氮艹卓类镇静催眠药,用于失眠的短效治疗。与苯二氮艹卓类的传统镇静催眠药不同,它选择性作用于BZ_1(ω_1)受体,无其它镇静催眠药所具有的诸多不良反应,且半衰期短,疗效好,无蓄积作用。 1 作用机理 在中枢神经系统中存在两种苯二氮艹卓受体亚型(BZ_1/BZ_2或ω_1/ω_2),BZ_1受体主要位于与镇静作用有关的大脑区     

盐酸丁螺环酮的研究现状

盐酸丁螺环酮是自30年前苯二氮(艹卓)类药物(BDZ)被采用以来,美国开发并用于临床的第一个非BDZ类抗焦虑药物,它具有和BDZ类药物相当的抗焦虑作用,但无催眠、抗痉挛和肌松弛效应,被称为“选择性抗焦虑剂”。它还属于抗抑郁药。在对盐酸丁螺环酮的近30年的实验研究和临床运用中,人们对它的化学结构、药效学、药代动力学、剂型研究等方面都有了不断深入和日臻完善的认识。作者拟就其上述几个方面做一简要综述。     

治疗精神疾病的药物

治疗精神疾病可用许多种药物,但常难于作出选择。本文根据临床对照试验的结果及医师的经验和意见作一介绍。 治疗焦虑的药物 焦虑是精神综合征(如抑郁或精神病)的一种症状,该综合征的特异性疗法通常比使用非特异性抗焦虑药(如苯二氮(艹卓)类)有效。需要药物治疗且与较特异的综合征无关的焦虑通常用一个苯二氮(艹卓)类药物治疗。虽然地西泮(安定,Valium)、氯氮(艹卓)(Librium)、阿普唑仑(Xandax)、氯氮(艹卓)酸     

帕罗西汀的临床应用进展

帕罗西汀是一种选择性 5 羟色胺再摄取阻滞药 ,为抗抑郁新药 ,具有疗效好、不良反应少等特点 ,一些大型临床研究证实它还可用于治疗惊恐发作、广泛性焦虑症、社交焦虑症、强迫症、失眠症、经前期综合征、早泄等其他疾病     

Triple uptake inhibitors: therapeutic potential in depression and beyond

Drugs that interfere with the uptake and/or metabolism of biogenic amines have been used to treat depression for > 4 decades. Early medications such as tricyclic antidepressants and monoamine oxidase inhibitors are effective but possess many side effects that limit their usefulness. Selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) are the results of rational design to find drugs that are as effective as the tricyclic antidepressants, but with more selectivity towards a single monoamine transporter. The SSRI class of drugs, which includes fluoxetine, paroxetine and sertraline, were previously viewed as the agents of choice for treating major depression. Recently, inhibitors of both serotonin and noradrenaline uptake ('dual uptake inhibitors'; SSRI/SNRI such as venlafaxine, duloxetine and milnacipran) have gained acceptance in the market. However, neither the SSRIs nor the SSRI/SNRI are fully satisfactory due to a delayed onset of action, low rate of response and side effect that can affect compliance. An important recent development has been the emergence of the triple uptake inhibitors (SSRI/SNRI/selective dopamine reuptake inhibitor), which inhibit the uptake of all three neurotransmitters that are most closely linked to depression: serotonin, noradrenaline and dopamine. Preclinical studies and clinical trials indicate that a drug inhibiting the uptake of all three of these neurotransmitters could produce a more rapid onset of action and possess greater efficacy than traditional antidepressants. This review discusses the evolution of biogenic amine-based therapies, the emerging strategies involved in the design and synthesis of novel triple uptake inhibitors as antidepressants and the therapeutic potential of triple uptake inhibitors.     

The Selective Serotonin Reuptake Inhibitor Paroxetine, but not Fluvoxamine, Decreases Methamphetamine Conditioned Place Preference in Mice

Monoamine transporters are the main targets of methamphetamine (METH). Recently, we showed that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), decreased METH conditioned place preference (CPP), suggesting that serotonin transporter (SERT) inhibition reduces the rewarding effects of METH. To further test this hypothesis, in the present study we investigated the effects of additional SSRIs, paroxetine and fluvoxamine, on METH CPP in C57BL/6J mice. In the CPP test, pretreatment with 20 mg/kg paroxetine abolished the CPP for METH, whereas pretreatment with 100 mg/kg fluvoxamine prior to administration of METH failed to inhibit METH CPP. These results suggest that paroxetine, a medication widely used to treat depression, may be a useful tool for treating METH dependence. Further, these data suggest that molecules other than the SERT [such as G protein-activated inwardly rectifying K+ (GIRK) channels] whose activities are modulated by paroxetine and fluoxetine, but not by fluvoxamine, are involved in reducing METH CPP by paroxetine and fluoxetine.     

Comparison of the anticholinergic effects of the serotonergic antidepressants,paroxetine, fluvoxamine and clomipramine

Paroxetine, a selective serotonin reuptake inhibitor, shows relatively high affinity for muscarinic acetylcholine receptors compared to other selective serotonin reuptake inhibitors. To determine whether paroxetine has anticholinergic effects in vivo, we examined the effects of paroxetine on oxotremorine-induced tremor, spontaneous defecation and passive avoidance performance using mice and compared the results with those using fluvoxamine, another selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant with serotonin selectivity. The potency of antidepressant activity as determined in the tail suspension test was paroxetine>fluvoxamine>clomipramine. Paroxetine and clomipramine inhibited oxotremorine-induced tremor, reduced spontaneous defecation and impaired passive avoidance performance, while fluvoxamine did not have similar effects. A comparison of ED(50) values showed that the ratio of anticholinergic effect to antidepressant activity was fluvoxamine, >3.2; paroxetine, 2.1-2.6; clomipramine, <0.8. These results suggest that paroxetine may induce fewer adverse anticholinergic effects than clomipramine, but more than fluvoxamine.     

Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug. A mean terminal elimination half-life of approximately 24 hours permits once daily administration. Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders. Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn. Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents. Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants. Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents. Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability. In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide. Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.     

Nonhormonal alternatives for the treatment of hot flashes

OBJECTIVE: To review the literature on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin for the treatment of hot flashes. DATA SOURCES: A MEDLINE search (January 1966-July 2003) was conducted to identify English-language literature available on the treatment of hot flashes that focused on clonidine, venlafaxine, selective serotonin reuptake inhibitors, and gabapentin. These articles, relevant abstracts, and additional references listed in articles were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA SYNTHESIS: In women unable or unwilling to take hormonal therapies, several nonhormonal alternatives have been evaluated in small controlled and uncontrolled trials. Oral and transdermal formulations of clonidine are moderately effective in reducing hot flashes. Results of studies evaluating venlafaxine, paroxetine, and gabapentin suggest greater reductions in hot-flash frequency and severity compared with those of clonidine. Fluoxetine appears to display a modest benefit compared with paroxetine, although no comparative trials have been conducted. Most women studied in these trials had a history of breast cancer, and many were taking concurrent tamoxifen. All of these agents were fairly well tolerated. CONCLUSIONS: Clonidine, venlafaxine, paroxetine, fluoxetine, and gabapentin are nonhormonal agents that have demonstrated efficacy in small controlled and uncontrolled trials in reducing hot flashes and should be considered in patients unwilling or unable to take hormonal therapies.     

Treatment benefits of duloxetine in major depressive disorder as assessed by number needed to treat

The efficacy of an antidepressant typically is assessed by comparing it with placebo using a validated rating scale. This type of analysis, however, does not translate well to the clinical settings. For clinicians, a more meaningful measure is the number needed to treat (NNT). The objective of this analysis is to assess the efficacy of duloxetine in terms of NNT. Data were obtained from nine clinical trials designed to assess the efficacy and safety of duloxetine as a treatment for major depressive disorder. These studies examined 8-9 weeks of acute treatment with duloxetine. NNT estimates were determined for duloxetine, selective serotonin reuptake inhibitor comparators from six multi-dose studies, and for duloxetine in patients > or =65 years of age. The NNT was based on the Hamilton Depression Rating Scale (HAMD17) for response and remission, and improvements defined by the Clinical Global Impression (CGI) were estimated and compared. The NNT was favorable for both duloxetine and selective serotonin reuptake inhibitor compared with placebo. The patients receiving duloxetine had NNT for HAMD17 response of 6.0, remission 7-9, and CGI-defined improvement 6-7 by 8 weeks. The NNTs for selective serotonin reuptake inhibitors (fluoxetine or paroxetine, 20 mg/day) were around 7 for response, 11 for remission, and 8 for CGI-defined improvement. The NNTs in the elderly were similar. The NNT for several measures of efficacy including remission consistently demonstrated the treatment benefits of duloxetine as well as of fluoxetine and paroxetine compared with placebo.     

Female Sexual Stimulation During Antidepressant Treatment

Three women with several diagnoses, including depression and psychosis, personality disorder, attention deficit hyperactivity disorder, alcohol abuse, and physical disease, were treated with selective serotonin reuptake inhibitors (fluoxetine, paroxetine, fluvoxamine). One patient was prescribed paroxetine in addition to methylphenidate. While receiving these agents, two women experienced undesirable sexual arousal and the third had increased sexual desire, arousal, and hypersexuality.     

The 5-HT(1A) receptor antagonist robalzotan completely reverses citalopram-induced inhibition of serotonergic cell firing.

5-HT(1A) receptor antagonists have been suggested to increase the efficacy of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors in the treatment of depression by enhancing the increase in brain 5-HT induced by 5-HT reuptake blockade. Here, the novel 5-HT(1A) receptor antagonist robalzotan [(R)-3-N, N-dicyclobutylamino-8-fluoro-3, 4-dihydro-2H-1-benzopyran-5-carboxamide hydrogen (2R, 3R) tartrate monohydrate] (12.5, 25, 50, 100 microg/kg, i.v.) was found to completely reverse the acute inhibitory effect of citalopram (300 microg/kg i.v.) or paroxetine (100 microg/kg, i.v.) on the activity of 5-HT neurons in the dorsal raphe nucleus in rats. Robalzotan (5, 50 microg/kg, i.v.) by itself increased the firing rate of the majority of 5-HT cells studied. The present results suggest that robalzotan may indeed augment the increases in 5-HT output induced by selective 5-HT reuptake inhibitors by antagonizing the feedback inhibition of 5-HT cell firing produced by such drugs. Thus, robalzotan may be effective by enhancing the action of selective 5-HT reuptake inhibitors or as monotherapy in the treatment of depression.     

Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients

Impaired cognitive functioning is often associated with major depressive disorder (MDD). Moreover, a number of agents used to treat MDD are known to have negative effects on cognitive functioning. We report an assessment of the effects of the selective norepinephrine reuptake inhibitor reboxetine, the selective serotonin reuptake inhibitor paroxetine, and placebo on a variety of measures of cognitive functioning in patients with MDD. Cognitive functioning in 74 adult patients (aged 18-65 years) with a confirmed diagnosis of MDD (DSM-IV) was assessed as part of two identical, randomized, double-blind, placebo- and active-treatment-controlled, fixed/flexible dose comparisons of 8 weeks of treatment with reboxetine (8-10 mg/day), paroxetine (20-40 mg/day) and placebo. Cognitive function was assessed at baseline, day 14 and day 56 using a selection of tasks from the Cognitive Drug Research computerized assessment system, including Simple Reaction Time, Digit Vigilance, Choice Reaction Time, Numeric Working Memory, Word Recognition and Critical Flicker Frequency. The results in the 74 patients (reboxetine n = 25, paroxetine n = 23, placebo n = 26) showed that reboxetine significantly improved the ability to sustain attention at day 56 compared with baseline (P = 0.023). In addition, patients who received reboxetine experienced significant improvements in their speed of cognitive functioning when tested at day 56 compared to baseline (P = 0.024). No significant changes or trends in this direction were seen among patients who received either placebo or paroxetine. The results of the present study provide objective data to support the possibility that reboxetine favourably affects cognitive processes in depressed patients.