Neuroscience iMed, AstraZeneca, USA.
Department of Psychiatry at the University of Kansas School of Medicine-Wichita, USA.
Curr Opin Pharmacol. 2014 Feb;14:6-10. doi: 10.1016/j.coph.2013.09.016. Epub 2013 Oct 19.
Given the lack of fundamental knowledge about the causes and pathophysiology of depression, it is a challenge for Phase I in antidepressant development to efficiently and thoroughly test new drugs. Initiation of Phase I should always be preceded by a careful consideration of what is known about the target and the molecule. While some early indicators of efficacy, such as the Emotional Test Battery, EEG markers, and fMRI correlates of anhedonia are available, further work is needed for their full incorporation in Phase I. Phase I studies of antidepressants should incorporate new measures and methods to the extent possible, and have the freedom to explore new hypotheses and move beyond the predetermined and inflexible study designs of traditional Phase I studies.
鉴于对抑郁症的病因和病理生理学缺乏基本认识，因此在抗抑郁药研发的第一阶段，有效地全面测试新药具有挑战性。在开始第一阶段之前，应该仔细考虑对靶点和分子的了解。虽然一些早期的疗效指标，如情绪测试电池、脑电图标记物和快感缺失的 fMRI 相关性已经可用，但仍需要进一步的工作来充分将其纳入第一阶段。抗抑郁药的第一阶段研究应尽可能纳入新的措施和方法，并具有探索新假设和超越传统第一阶段研究预定和僵化设计的自由。
