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强迫症的药物治疗

Pharmacologic therapy of obsessive compulsive disorder.

作者信息

DeVeaugh-Geiss J

机构信息

Glaxo Research Institute Glaxo, Inc. Research Triangle Park, North Carolina 27709.

出版信息

Adv Pharmacol. 1994;30:35-52. doi: 10.1016/s1054-3589(08)60171-4.

Abstract

OCD is an anxiety disorder that was once viewed as rare and very difficult to treat. Although the first evidence that a serotonergic drug, clomipramine, might be effective in treating symptoms of OCD was published by Fernandez-Cordoba and Lopez-Ibor Alino in 1967, controlled trials demonstrating the efficacy of pharmacologic treatments in OCD did not appear until the 1980s. The availability of potentially effective treatments, combined with the awareness of prevalence rates for the disorder that are higher than previously believed, led to considerable interest in OCD. Numerous studies have been undertaken to investigate the biology of OCD. The observation that drugs that act by inhibiting serotonin uptake, such as clomipramine, fluvoxamine, sertraline, and fluoxetine, are effective in treating symptoms of OCD has resulted in intense interest in the relationship between serotonin and this disorder. Several lines of investigation support a serotonergic hypothesis for the pathophysiology and treatment of this disorder. Clomipramine, a tricyclic antidepressant that is a potent serotonin uptake inhibitor, was the first pharmacologic treatment for OCD to be studied in large multicenter trials. The successful outcome of these studies resulted in marketing approval by the United States Food and Drug Administration in 1989. Subsequently, similar multicenter trials have been undertaken with the selective serotonin uptake inhibitors fluvoxamine, sertraline, and fluoxetine. Results from these multicenter trials indicate that all these drugs are more effective than placebo in treating OCD. However, meta-analytic techniques applied to the data from controlled trials of these drugs suggest that the effect size for clomipramine is somewhat larger than that of the selective serotonin uptake inhibitors. A number of other drugs that affect serotonin through mechanisms other than uptake inhibition have been tried as treatments for OCD. Because of the small size of many of these studies, it is difficult to evaluate them in the context of the multicenter trials that studied hundreds of patients. Nevertheless, there may be a role for other serotonergic drugs in the treatment of OCD, particularly as adjunctive treatments used to enhance the effect of the serotonin uptake inhibitors. The data supporting the use of adjunctive treatment are limited and cannot be considered to demonstrate definitively the value of augmentation strategies with adjunctive treatment. Nevertheless, the serotonin uptake inhibitors, although effective in a large number of patients, do not appear to provide adequate symptom relief for some patients. Furthermore, among the patients who do respond to serotonin uptake inhibitors, complete remission in uncommon, which leaves a need for improvement of therapies.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

强迫症是一种焦虑症,曾被视为罕见且极难治疗。尽管1967年费尔南德斯 - 科尔多瓦和洛佩斯 - 伊博尔·阿利诺发表了首个证据,表明一种血清素能药物氯米帕明可能对治疗强迫症症状有效,但直到20世纪80年代才出现证明药物治疗强迫症有效性的对照试验。有效的潜在治疗方法的出现,加上对该疾病患病率高于先前认知的认识,引发了对强迫症的广泛关注。人们进行了大量研究来探究强迫症的生物学机制。观察发现,像氯米帕明、氟伏沙明、舍曲林和氟西汀等通过抑制血清素摄取起作用的药物对治疗强迫症症状有效,这引发了人们对血清素与该疾病之间关系的浓厚兴趣。多项研究支持血清素能假说在该疾病病理生理学和治疗中的作用。氯米帕明是一种三环类抗抑郁药,也是一种强效的血清素摄取抑制剂,是首个在大型多中心试验中研究的强迫症药物治疗方法。这些研究的成功结果导致其于1989年获得美国食品药品监督管理局的上市批准。随后,针对选择性血清素摄取抑制剂氟伏沙明、舍曲林和氟西汀也进行了类似的多中心试验。这些多中心试验的结果表明,所有这些药物在治疗强迫症方面都比安慰剂更有效。然而,对这些药物对照试验数据应用荟萃分析技术表明,氯米帕明的效应量比选择性血清素摄取抑制剂略大。许多通过摄取抑制以外机制影响血清素的其他药物也被尝试用于治疗强迫症。由于其中许多研究规模较小,难以在研究数百名患者的多中心试验背景下对其进行评估。尽管如此,其他血清素能药物在强迫症治疗中可能有作用,特别是作为辅助治疗来增强血清素摄取抑制剂的效果。支持使用辅助治疗的数据有限,不能明确证明辅助治疗增强策略的价值。然而,血清素摄取抑制剂虽然对大量患者有效,但对一些患者似乎并未提供足够的症状缓解。此外,在对血清素摄取抑制剂有反应的患者中,完全缓解并不常见,这使得仍有必要改进治疗方法。(摘要截选至400字)

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