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[从创伤生物学到创伤后应激障碍的二级预防性药物措施]

[From the biology of trauma to secondary preventive pharmalogical measures for post-traumatic stress disorders].

作者信息

Ducrocq F, Vaiva G

机构信息

Psychiatre, praticien hospitalier, Cellule d'Urgence Médico-Psychologique, SAMU Régional de Lille, Clinique Universitaire de Psychiatrie, CHRU de Lille, 59037 Lille cedex.

出版信息

Encephale. 2005 Mar-Apr;31(2):212-26. doi: 10.1016/s0013-7006(05)82388-7.

DOI:10.1016/s0013-7006(05)82388-7
PMID:15959448
Abstract

Of all the psychological complications that an individual is likely to present with when confronted with an exceptional event, the Post-Traumatic Stress Disorder is characterized by being progressive, frequent, invalidating, strongly associated with comorbidity, and having the tendency to become chronic if it is not detected clinically. By definition, it is threatening and produces an intense fear reaction. The traumatic event is a situation of extreme stress, not only capable of altering the physical and psychological homeostasis of the individual, but is also recognized as determinant in the aetiopathology of complications. The intensity of this distress can be identified clinically and physiologically, and is currently considered as an important risk factor for the development of PTSD later on, together with other pre-, peri- and post-traumatic factors. In fact, the most studied field is the therapeutic approach, in particular drug treatment, of the fully-constituted disorder, although this actually represents tertiary prevention. Even though primary prevention seems to concern Medicine very little, any prospect of performing secondary prevention should begin by rapid identification of the risk or vulnerability factors and should allow a population at risk from developing complications to be defined. Its potential therapeutic impact brings together psychotherapeutic and drug treatment, since it is only this combination that seems able to allow the most favourable clinical outcome to be achieved for an individual, who is confronted by an out-of-the-ordinary event. The aims of secondary prevention strategies are, for example, to reduce the incidence of acute PTSD in patients seen following the event. The benefits for the individual and for the society can easily be measured in terms of the consequences on his/her social, professional and family life, or in terms of cost. The usefulness of this prevention can also be measured by the possible ways that other conditions, comorbid to PTSD, are controlled, such as anxiety disorders, depression and substance abuse, for example. Secondary prevention strategies may also be aimed at determining the therapeutic impact, by preventing or moderating the appearance of an acute stress, or even by contributing in avoiding the onset of chronic PTSD. Psychopharmacology of the immediate and post-immediate disorders, however, remains a field which has been studied very little. Reduction or control of the high, prolonged level of hyperarousal phenomena or hypersensitization of the hypothalamo-pituitary axis, would contribute to the comfort of the individual, and would participate in the prevention of PTSD. Based on current knowledge of the neurobiology of trauma, we look into the existing and potential pharmacological possibilities. Even though benzodiazepines tend to have an important role, knowledge of other drugs and therapeutic groups is rapidly increasing. In this review, we will see that the efficacy of anti-adrenergic drugs and certain other anxiolytics is now well-documented, this opening the door to their use in the future. Other drug groups offer interesting, well-proven approaches, such as serotoninergic drugs, CRF or NPY antagonists, NMDA antagonists, anticonvulsants or other GABAergic agents. In view of this disorder, which represents a true public health problem, we consider that it is now possible to widen the horizons of our drug therapy, in combination with any necessary psychotherapeutic treatment, to reach the heart of the traumatic event, that often upsets the victims, both by the psychological suffering it induces, and the loss of his/her social, family and professional references and support structures.

摘要

在个体遭遇特殊事件时可能出现的所有心理并发症中,创伤后应激障碍具有以下特点:呈进行性、频发、致残、与共病密切相关,若未得到临床诊断,有发展为慢性疾病的倾向。根据定义,它具有威胁性,并会引发强烈的恐惧反应。创伤性事件是一种极端应激情况,不仅能够改变个体的生理和心理平衡,而且在并发症的病因病理学中被认为是决定性因素。这种痛苦的强度可以通过临床和生理手段识别,目前被视为创伤后应激障碍后期发展的重要风险因素,与其他创伤前、创伤中和创伤后因素一起。事实上,研究最多的领域是已完全形成的疾病的治疗方法,特别是药物治疗,尽管这实际上属于三级预防。尽管一级预防似乎很少受到医学关注,但任何二级预防的前景都应始于快速识别风险或脆弱因素,并应能够确定有发生并发症风险的人群。其潜在的治疗影响涉及心理治疗和药物治疗,因为只有这种结合似乎能够为遭遇异常事件的个体带来最有利的临床结果。二级预防策略的目标,例如,是降低事件后就诊患者中急性创伤后应激障碍的发病率。对个人和社会的益处可以很容易地从对其社会、职业和家庭生活的影响或成本方面来衡量。这种预防的有用性也可以通过控制与创伤后应激障碍共病的其他病症的可能方式来衡量,例如焦虑症、抑郁症和药物滥用。二级预防策略还可能旨在通过预防或减轻急性应激的出现,甚至通过有助于避免慢性创伤后应激障碍的发作来确定治疗效果。然而,即时和即时后疾病的精神药理学仍然是一个研究很少的领域。降低或控制高的、持续的过度觉醒现象水平或下丘脑 - 垂体轴的超敏反应,将有助于个体的舒适,并有助于预防创伤后应激障碍。基于目前对创伤神经生物学的认识,我们研究现有的和潜在可用的药物可能性。尽管苯二氮䓬类药物往往具有重要作用,但对其他药物和治疗组的了解正在迅速增加。在这篇综述中,我们将看到抗肾上腺素能药物和某些其他抗焦虑药物的疗效现在已有充分记录,这为它们未来的使用打开了大门。其他药物组提供了有趣的、经过充分验证的方法,如果血清素能药物、促肾上腺皮质激素释放因子或神经肽Y拮抗剂、N - 甲基 - D - 天冬氨酸拮抗剂、抗惊厥药或其他γ - 氨基丁酸能药物。鉴于这种代表真正公共卫生问题的疾病,我们认为现在有可能扩大我们药物治疗的视野,结合任何必要的心理治疗,深入到创伤事件的核心,创伤事件常常使受害者感到不安,这不仅是因为它引发的心理痛苦,还因为其社会、家庭和职业参考及支持结构的丧失。

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