New York University School of Medicine, Department of Psychiatry , New York, NY , USA.
Expert Opin Investig Drugs. 2015 May;24(5):659-72. doi: 10.1517/13543784.2015.1020109. Epub 2015 Mar 14.
Posttraumatic stress disorder (PTSD) is a prevalent, chronic and disabling anxiety disorder that may develop following exposure to a traumatic event. There is currently no effective pharmacotherapy for PTSD and therefore the discovery of novel, evidence-based treatments is particularly important. This review of potential novel treatments could act as a catalyst for further drug investigation.
In this review, the authors discuss the heterogeneity of PTSD and why this provides a challenge for discovering effective treatments for this disorder. By searching for the neurobiological systems that are disrupted in individuals with PTSD and their correlation with different symptoms, the authors propose potential pharmacological treatments that could target these symptoms. They discuss drugs such as nabilone, d-cycloserine, nor-BNI, 7,8-dihydroxyflavone and oxytocin (OT) to target systems such as cannabinoids, glutamate, opioids, brain-derived neurotrophic factor and the OT receptor, respectively. While not conclusive, the authors believe that these brain systems include promising targets for drug discovery. Finally, the authors review animal studies, proof-of-concept studies and case studies that support our proposed treatments.
A mechanism-based approach utilizing techniques such as in vivo neuroimaging will allow for the determination of treatments. Due to the heterogeneity of the PTSD phenotype, focusing on symptomology rather than a categorical diagnosis will allow for more personalized treatment. Furthermore, there appears to be a promise in drugs as cognitive enhancers, the use of drug cocktails and novel compounds that target specific pathways linked to the etiology of PTSD.
创伤后应激障碍(PTSD)是一种普遍存在的、慢性的、使人丧失能力的焦虑障碍,可能是在经历创伤事件后发展而来的。目前,PTSD 没有有效的药物治疗方法,因此,发现新的、基于证据的治疗方法尤为重要。对潜在新疗法的综述可以作为进一步药物研究的催化剂。
在这篇综述中,作者讨论了 PTSD 的异质性,以及为什么这对发现这种疾病的有效治疗方法构成了挑战。通过寻找在 PTSD 患者中受到干扰的神经生物学系统,以及它们与不同症状的相关性,作者提出了可能针对这些症状的潜在药物治疗方法。他们讨论了诸如纳布啡、D-环丝氨酸、去甲-BNI、7,8-二羟基黄酮和催产素(OT)等药物,分别针对大麻素、谷氨酸、阿片类药物、脑源性神经营养因子和 OT 受体等系统。虽然没有定论,但作者认为这些大脑系统包括有希望的药物发现靶点。最后,作者综述了支持我们提出的治疗方法的动物研究、概念验证研究和案例研究。
利用活体神经影像学等技术的基于机制的方法将允许确定治疗方法。由于 PTSD 表型的异质性,关注症状而不是分类诊断将允许更个性化的治疗。此外,作为认知增强剂的药物、使用药物鸡尾酒和针对与 PTSD 病因相关的特定途径的新型化合物似乎有希望。