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丁丙诺啡反应作为神经遗传多态性前因的函数:多巴胺基因会影响奖赏缺乏综合征(RDS)的临床结果吗?

Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?

作者信息

Blum Kenneth, Oscar-Berman Marlene, Jacobs William, McLaughlin Thomas, Gold Mark S

机构信息

Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA ; Human Integrated Services Unit University of Vermont Centre for Clinical & Translational Science, College of Medicine, Burlington, VT, USA ; Department of Addiction Research & Therapy, Malibu Beach Recovery Centre, Malibu Beach, CA, USA ; Dominion Diagnostics, LLC, North Kingstown, RI, USA ; Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India ; IGENE, LLC, Austin, Texas, USA.

Departments of Psychiatry, Neurology, and Anatomy & Neurobiology, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, 02118, USA.

出版信息

J Addict Res Ther. 2014;5. doi: 10.4172/2155-6105.1000185.

Abstract

There is a plethora of research indicating the successful treatment of opioid dependence with either buprenorphine alone or in combination with naloxone (Suboxone®). However, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal (even with tapering of the dosage of for example Suboxone® which is 40 times more potent than morphine) from low dose of buprenorphine (alone or with naloxone). In addition our findings of a long-term flat affect in chronic Suboxone® patients amongst other unwanted side effects including diversion and suicide attempts provides impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient's clinical experience and benefits during opioid replacement therapy.

摘要

有大量研究表明,单独使用丁丙诺啡或与纳洛酮联合使用(舒倍生®)可成功治疗阿片类药物依赖。然而,尽管目前缺乏美国食品药品监督管理局(FDA)批准的其他阿片类维持化合物,我们仍鼓励谨慎使用这些药物进行长期维持治疗。我们的担忧得到了以下情况的支持:即使是低剂量的丁丙诺啡(单独使用或与纳洛酮联合使用),也会出现严重戒断反应(即使逐渐减少例如舒倍生®的剂量,其效力比吗啡强40倍)。此外,我们发现长期使用舒倍生®的慢性患者会出现情感平淡,以及其他不良副作用,包括药物转移和自杀企图,这促使我们重新考虑长期使用。然而,采用基因检测来揭示奖赏回路基因多态性,尤其是那些与多巴胺能途径以及阿片受体相关的多态性,似乎是谨慎之举,以此作为改善治疗效果的一种方式。了解奖赏回路参与丁丙诺啡作用与各自基因型之间的相互作用,为增强患者在阿片类药物替代治疗期间的临床体验和益处提供了一个新的框架。

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