Washington University School of Medicine, Department of Psychiatry, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110, USA; Saint Louis University School of Medicine, Department of Neurology & Psychiatry, 1438 South Grand Boulevard, St. Louis, MO 63104, USA.
Saint Louis University School of Medicine, Department of Neurology & Psychiatry, 1438 South Grand Boulevard, St. Louis, MO 63104, USA.
Psychiatry Res. 2014 Mar 30;221(3):231-9. doi: 10.1016/j.pscychresns.2014.01.003. Epub 2014 Jan 14.
Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentation remains ill-defined. In vivo animal studies and in vitro human studies using cloned dopamine dopamine D2 receptors suggest aripiprazole is a partial dopamine agonist; in this preliminary neuroimaging trial, we hypothesized that aripiprazole's antidepressant augmentation efficacy arises from dopamine partial agonist activity. To test this, we assessed the effects of aripiprazole augmentation on the cerebral utilization of 6-[(18)F]-fluoro-3,4-dihydroxy-l-phenylalanine (FDOPA) using positron emission tomography (PET). Fourteen depressed patients, who had failed 8 weeks of antidepressant therapy with selective serotonin reuptake inhibitors, underwent FDOPA PET scans before and after aripiprazole augmentation; 11 responded to augmentation. Whole brain, voxel-wise comparisons of pre- and post-aripiprazole scans revealed increased FDOPA trapping in the right medial caudate of augmentation responders. An exploratory analysis of depressive symptoms revealed that responders experienced large improvements only in putatively dopaminergic symptoms of lassitude and inability to feel. These preliminary findings suggest that augmentation of antidepressant response by aripiprazole may be associated with potentiation of dopaminergic activity.
几项双盲、前瞻性试验已经证明，阿立哌唑在对标准抗抑郁治疗反应不佳的抑郁患者中具有抗抑郁增效作用。尽管阿立哌唑现在被广泛用于这种适应症，并且对其受体结合特性有了很多了解，但它的抗抑郁增效机制仍不清楚。体内动物研究和使用克隆多巴胺 D2 受体的体外人体研究表明，阿立哌唑是一种部分多巴胺激动剂；在这项初步的神经影像学试验中，我们假设阿立哌唑的抗抑郁增效作用源于多巴胺部分激动剂活性。为了验证这一点，我们评估了阿立哌唑增效对正电子发射断层扫描（PET）中 6-[(18)F]-氟-3,4-二羟基-l-苯丙氨酸（FDOPA）脑利用率的影响。14 名接受选择性 5-羟色胺再摄取抑制剂治疗 8 周后仍未缓解的抑郁患者在接受阿立哌唑增效治疗前后接受了 FDOPA PET 扫描；11 名患者对增效治疗有反应。阿立哌唑增效前后的全脑、体素比较显示，增效反应者右侧内囊尾状核的 FDOPA 捕获增加。对抑郁症状的探索性分析表明，反应者仅在疲劳和无法感觉等假定的多巴胺症状方面有很大改善。这些初步发现表明，阿立哌唑增强抗抑郁反应可能与增强多巴胺活性有关。
