Clinical pharmacology in the development of new antidepressants: the challenges.

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.