美沙酮使用障碍患者中，纳曲酮长效制剂对药物相关刺激的大脑反应的影响。
Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.
机构信息
From the Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
出版信息
J Psychiatry Neurosci. 2018 Jul;43(4):254-261. doi: 10.1503/jpn.170036.
BACKGROUND
Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.
METHODS
Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.
RESULTS
We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.
LIMITATIONS
The study was not placebo-controlled owing to ethical, safety and feasibility concerns.
CONCLUSION
Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.
背景
对与药物相关线索的高度反应是成瘾的一个标志。缓释纳曲酮（XR-NTX）是美国食品和药物管理局批准的用于预防阿片类药物使用障碍（OUD）患者复发的药物治疗。在这些患者中，已经证明 XR-NTX 可减少与阿片类药物相关的视觉刺激引起的大脑反应。为了评估这种现象的生物标志物潜力，有必要确定这种效应是否仅限于与阿片类药物相关的刺激，以及它是否与关键的 OUD 症状有关。
方法
使用功能磁共振成像（fMRI），我们在接受 XR-NTX 治疗之前、期间和之后，测量了已戒毒的 OUD 患者对与阿片类药物相关和对照（即性和厌恶）图像的大脑反应。在每次治疗过程中，使用临床医生和自我管理工具评估成瘾和戒断严重程度。
结果
我们对 24 名 OUD 患者进行了分析。在 XR-NTX 治疗期间，我们发现伏隔核（NAcc）和内侧眶额皮质（mOFC）对与阿片类药物相关的刺激的反应降低。mOFC 反应的减少是与阿片类药物相关的刺激特异性的。NAcc 和 mOFC 中与阿片类药物相关的线索反应性降低与临床评估和自我报告的戒断症状减少分别相关。
局限性
由于伦理、安全和可行性方面的考虑，该研究没有安慰剂对照。
结论
缓释纳曲酮降低了 OUD 患者的 NAcc 和 mOFC 线索反应性。这种效应仅在 mOFC 中是与阿片类药物相关的刺激特异性的。对与阿片类药物相关的刺激的神经反应降低在戒断严重程度下降更大的患者中更为明显。我们的结果支持中边缘皮质线索反应性在监测 XR-NTX 治疗结果中的临床应用，并强调了阿片类药物戒断症状与神经阿片类药物线索反应性之间的联系。
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