抑郁症治疗药物研究的最新进展

抑郁症是临床上一种十分常见的精神类疾病,近年来其发病率也是在不断上升中。而且此病的治疗十分困难。目前用于抑郁症治疗的药物主要有:三环类抗抑郁药物、单胺氧化酶抑制剂、5-HT及NA再摄取抑制药(SNRIs)、NA及NA再摄取抑制药(NDRIs)以及最新发现的新靶点类药物神经类固醇、吲哚胺2,3-双加氧酶以及激素类药物等。本文就近年来抗抑郁药研究的进展以及各药物对抑郁症的治疗效果作一综述。     

抗抑郁药物的研究概况

综述了抗抑郁药物的作用机制（单胺递质理论、神经递质受体理论、受体后神经细胞信号转导理论）、药物分类（三环类、单胺氧化酶抑制剂、可逆性单胺氧化酶抑制剂、选择性5-HT再摄取抑制剂、选择性NA再摄取抑制剂、5-HT和NA双重再摄取抑制剂、NA能和特异性5-HT能抗抑郁药等）及研究现状。     

抗抑郁药历史与研究进展

自20世纪50年代以来,抗抑郁药研究进展迅速。该文对抗抑郁药的历史分类、化学结构分类和作用机制分类等进行了简要介绍,并对新型抗抑郁药选择性5 羟色胺（5 HT）再摄取抑制药、5 HT再吸收促进药、选择性5 HT与去甲肾上腺素（NA）再摄取抑制药、去甲肾上腺素能和特异性5 HT能抑制药、 去甲肾上腺素能和多巴胺能摄取抑制药、新型可逆性单胺氧化酶抑制药（MAOI）、新三环类抗抑郁药、天然与中草药抗抑郁药研究进展进行了较详细介绍。     

单胺重摄取抑制剂的研究进展

单胺重摄取抑制剂在临床上被广泛应用于抑郁症的治疗。本文通过文献检索综述了2004～2010年间5-羟色胺重摄取抑制剂和去甲肾上腺素再摄取抑制剂的研究进展,发现具有5-HT、NA重摄取抑制(选择性抑制或双重抑制)活性的新结构及部分构效关系。     

单胺重摄取抑制剂的研究进展

单胺重摄取抑制剂在临床上被广泛应用于抑郁症的治疗.本文通过文献检索综述了2004～2010年间5-羟色胺重摄取抑制剂和去甲肾上腺素再摄取抑制剂的研究进展,发现具有5-HT、NA重摄取抑制(选择性抑制或双重抑制)活性的新结构及部分构效关系.     

抗抑郁药:换用抗抑郁药时发生药物相互作用的风险

澳大利亚ADRAC发出警告称,关于换用抗抑郁药时可能因药物相互作用而影响转归,包括发生5羟色胺综合征。抗抑郁药包括选择性5羟色胺再摄取抑制药(SSRI)、三环类抗抑郁药(TCA)、单胺氧化酶抑制药(MADI)、去甲肾上腺     

抗抑郁药

目前，治疗抑郁症的药物主要有3大类：调节脑内5-羟色胺（5-HT）和去甲肾上腺素（NE）平衡的三环类、减缓这些脑内神经递质降解的单胺氧化酶抑制剂和增强5-HT活性但不影响其他神经递质的选择性5-HT再摄取抑制剂。文拉法辛（venlafaxine）是一种三环类化合物，于1994年上市，是第一个5-HT和NE再摄取抑制剂。尤其作为严重抑郁症的一线治疗药具有特殊的功效。     

抗抑郁症药介绍

抑郁症为临床常见的精神障碍,其发病可能与脑内神经递质或受体功能紊乱有关,主要是大脑5-羟色胺(5-HT)和去甲肾上腺素(NA)等神经递质含量的减少[1]。抑郁症的诊断目前尚无客观的实验室证据,主要根据病人的病史和临床症状,如情绪低落,并出现许多伴随症状,而且程度严重、旷日持久,造成病人社会功能受损,或者给病人造成痛苦或不良后果。抑郁症的治疗有多种方式,但以药物治疗为主。治疗药物从上世纪50年代的第一代单胺氧化酶抑制药(MAOI)发展到目前的第三代选择性5-HT再摄取抑制药(SSRI),尤其是80年代以后开发的SSRI,具有安全、有效、不…     

抑郁症治疗进展

本文对抑郁症的治疗进展作了系统综述。选择性5-羟色胺(HT)再摄取抑制剂(SSRI)疗效确定且不良反应少,是目前应用最广泛的抗抑郁药。作用于多种神经递质系统的药物如5-HT／去甲肾上腺素(NE)再摄取抑制剂(SNRI)、NE和特异性5-HT能抗抑郁药(NaSSA)等也有确切的疗效。对于难治性抑郁症,一般需加用锂盐、非典型抗精神病药物等。各种抗抑郁药的疗效仍不够理想,大多数起效时间较慢,症状缓解不彻底。药物与心理联合治疗将明显提高疗效。     

抗抑郁药Desvenlafaxine

目前,治疗抑郁症的药物主要有3大类:调节脑内5-羟色胺(5-HT)和去甲肾上腺素(NE)平衡的三环类、减缓这些脑内神经递质降解的单胺氧化酶抑制剂和增强5-HT活性但不影响其他神经递质的选择性5-HT再摄取抑制剂.     

Pharmacological management of treatment-resistant obsessive-compulsive disorder

Once considered rare and resistant to treatment, obsessive-compulsive disorder (OCD) has now emerged as a common, yet often unrecognized, psychiatric condition. Treatment with selective serotonin reuptake inhibitors (SSRIs) is effective in 40-60% of patients with OCD. Management of the remaining 40-60% of patients with treatment-resistant OCD is challenging. We review up-to-date evidence focusing on strategies for treatment-resistant OCD, including increasing the dose of SSRI, switching to another SSRI, augmentation with antipsychotics, and the use of serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs). Finally, we provide a flow chart, which includes nonpharmacological interventions such as cognitive-behavioural therapy, family interventions and physical interventions such as neurosurgery and deep brain stimulation, alongside the pharmacological strategies.     

Hypertensive urgency induced by an interaction of mirtazapine and clonidine

Mirtazapine is a new antidepressant with a tetracyclic chemical structure that is not related to selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors. The antidepressant effect results from stimulation of the noradrenergic system through antagonism at central (alpha2-inhibitory receptors. Clonidine exerts its antihypertensive effect by stimulating these receptors to cause a reduction in endogenous release of norepinephrine. Therefore, the two agents have mechanisms of action that potentially oppose one another. We report a case of hypertensive urgency that ensued after a patient stabilized on clonidine began taking mirtazapine.     

抗抑郁药的研究新进展

抑郁症正成为一个严重的全球问题。目前抗抑郁药物分四大类：单胺氧化酶抑制剂（Monoamine oxidase inhibitors,MAOIs）、三环类药物（Tricyclicantide pressants,TCAs）、选择性5-色胺再摄取抑制剂（Selective serotonin reuptake inhibitors,SSRIs）、新型抗抑郁药。     

Expanding the horizons of depression: beyond the monoamine hypothesis

The monoamine hypothesis has dominated our understanding of depression and of pharmacological approaches to its management and it has produced several generations of antidepressant agents, ranging from the monoamine oxidase inhibitors (MAOIs), through tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs), to the recently introduced selective noradrenaline reuptake inhibitor (NARI), reboxetine. Greater receptor selectivity has improved tolerability, but not efficacy, when newer compounds are compared with the original tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. Essentially, the newer antidepressants have the same distinguishing feature as older ones, i.e. acute enhancement of monoaminergic neurotransmission. The monoamine hypothesis cannot conclusively link the acute biochemical action of antidepressants on monoamine levels with their delayed clinical effect of 10-14 days, nor can it explain the mode of action of antidepressants that are effective despite being very weak inhibitors of monoaminergic transmission (e.g. iprindole) or, incongruously, enhancing monoamine uptake (e.g. tianeptine). Compared with other fields of medicine, there has been a lack of progress in understanding the pathophysiology of depression and producing truly novel antidepressant agents. Other biological approaches to depression, such as overactivity of the hypothalamic-pituitary-adrenal axis, hippocampal neural plasticity in response to stress, and the link between the inflammatory response and depression, offer new approaches to finding pharmacological agents, aided by improved techniques for visualising the human brain, better animal models, and increased knowledge of human markers of depression. Copyright 2001 John Wiley & Sons, Ltd.     

Orthostatic Hypotension Induced by Sertraline Withdrawal

Sertraline is a member of the newest class of antidepressants, the selective serotonin reuptake inhibitors. Due to its inherent selectivity and its lack of action with norepinephrine, dopamine, monoamine oxidase, and cholinergic receptors, this drug is unlikely to have any cardiovascular activity. A patient receiving sertraline for depression developed dizziness and orthostatic hypotension on repeated attempts to discontinue the drug. All other organic factors were ruled out. The hypotension was proved to be secondary to sertraline by repeated rechallenges. After a variety of attempted treatments, the agent was discontinued successfully through an extended titration period. This report should guide clinicians in treating patients with a similar problem.     

Efficacy of administration of dexfenfluramine and phentermine, alone and in combination, on ingestive behavior and body weight in rats

 Cocaine, which non-selectively blocks the reuptake of the monoamines serotonin, dopamine and norepinephrine, produces weak antinociceptive effects and increases the antinociceptive effects of low- to intermediate-efficacy mu opioid agonists in rhesus monkeys. In the present study, the antinociceptive effects of more selective monoamine reuptake inhibitors administered alone and in combination with mu opioid agonists were evaluated in rhesus monkeys using a warm-water tail-withdrawal assay of thermal nociception. Like cocaine, the selective serotonin reuptake inhibitors clomipramine (0.01–3.2 mg/kg) and fluoxetine (0.1–10 mg/kg) produced weak antinociceptive effects. Pretreatment with the serotonin receptor antagonist mianserin (0.032–0.32 mg/kg) produced rightward and downward shifts in the clomipramine dose-effect curve, suggesting that the effects of clomipramine were mediated by serotonin receptors. Combination of clomipramine with the low efficacy mu agonist nalbuphine or the intermediate efficacy mu agonist morphine produced more antinociception than did the mu agonists alone. Fluoxetine also produced a small leftward shift in the morphine dose-effect curve. The selective norepinephrine reuptake inhibitors nisoxetine (0.1–10 mg/kg) and tomoxetine (0.1–10 mg/kg) and the selective dopamine reuptake inhibitors bupropion (0.032–3.2 mg/kg) and GBR 12909 (0.1–10 mg/kg) did not produce antinociception or increase antinociception induced by nalbuphine or morphine. In fact, GBR 12909 produced dose-dependent allodynia and reduced the maximal antinociceptive effects of morphine. These results suggest that inhibition of serotonin reuptake is sufficient to produce weak antinociceptive effects and enhance the antinociceptive effects of low efficacy mu opioid agonists. These results also suggest that the effects of cocaine on serotonin reuptake may contribute to cocaine’s antinociceptive effects in rhesus monkeys. Received: 5 May 1997 / Final version: 30 July 1997     

Orphan comparisons and indirect meta-analysis: a case study on antidepressant efficacy in dysthymia comparing tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors by using general linear models

Direct comparisons of the efficacy of competing interventions are not always available in the literature. This situation leads to the presence of clinically relevant "orphan comparisons" of therapeutic interventions which have never been compared head-to-head. To overcome this limitation, simple methods for indirect meta-analysis have been suggested. Nevertheless, their results are prone to bias when more than 1 indirect comparison is tested because of the likely duplication of data for some comparisons. In contrast, general linear models can be used to extend simple indirect meta-analysis beyond 1 indirect comparison by fitting to incomplete data using maximum likelihood within the framework of multitreatment comparisons. This study presents a tutorial application of general linear models to the comparative efficacy of several antidepressants in dysthymia (tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors. Working with previously published data comparing the efficacy of antidepressants with placebo, it is shown that tricyclic antidepressants and selective serotonin reuptake inhibitors present similar efficacy (odds ratio = 1.19, P = 0.37; relative risk = 1.10, P = 0.24; risk difference = 0.03, P = 0.53), whereas monoamine oxidase inhibitors outperform both tricyclic antidepressants and selective serotonin reuptake inhibitors, at least for some effect scales (odds ratio = 1.57, P = 0.05; relative risk = 1.25, P = 0.05; risk difference = 0.09, P = 0.08). This finding, which is an instance of a relevant orphan comparison and could not be obtained otherwise, could motivate the conduct of clinical trials or focused systematic reviews to support or refute its importance through appropriate head-to-head comparisons.     

Phaeochromocytoma unmasked by drug therapy

(1) Phaeochromocytoma is a benign or malignant tumour that stores and produces catecholamines (adrenaline and noradrenaline, and their metabolites metanephrine and normetanephrine). (2) Phaeochromocytoma can be unmasked by some drugs. (3) Metoclopramide and other neuroleptics are most often implicated. Other drugs include antidepressants (such as selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and imipramine), betablockers, opioids, and curare.     

Citalopram in the treatment of depression and other potential uses in psychiatry.

During the past decade, treatment options for depression have increased with the introduction of new agents. Older agents, such as tricyclic antidepressants and monoamine oxidase inhibitors, increase noradrenergic and serotonergic neurotransmission. Attempts to separate antidepressant effects from adverse effects led to the development of selective serotonin reuptake inhibitors (SSRIs). Citalopram is the newest SSRI to be marketed in the United States. Of all SSRIs on the market, it is the most selective for serotonin reuptake pump. Its efficacy in treating depression was evident in both placebo-controlled and comparator trials. In addition, citalopram was studied in the treatment of other psychiatric disorders. The agent has less inhibition of cytochrome P450 enzymes than other SSRIs, possibly giving it a lower potential for drug interactions.     

Biochemical profile in patients with anxious depression under the treatment with serotonergic antidepressants with different mechanisms of action

The pharmacodynamics of serotonergic antidepressants that differentially influence serotonin reuptake transporters is poorly investigated. The aim of this study was to compare the biochemical profiles in patients with anxious depression under the treatment with tianeptine, a serotonin reuptake enhancer, and sertraline, a selective serotonin reuptake inhibitor. Platelet monoamine oxidase (MAO) and serum amine oxidase (AO) activities, concentration of middle-mass endotoxic molecules (MMEM) and parameters that characterize the functional properties of serum albumin were investigated in 43 patients with anxious depression (ICD-10: F 32.1 and F 33.1). It was established that, in comparison with healthy controls, patients with anxious depression were characterized by the significant increase in MAO activity (by 95%), MMEM concentration (by 86%), and a significant decrease in AO activity (by 43%) and also in functional albumin activity. The results of the study show that both tianeptine and sertraline are equally effective in the treatment of anxious depression. The present biochemical investigation, however, suggests that the underlying biochemical changes are more complete following tianeptine treatment.