Back to the Future of Neuropsychopharmacology.

Disappointments in translating preclinical findings into clinical efficacy have triggered a number of changes in neuroscience drug discovery ranging from investments diverted to other therapeutic areas to reduced reliance on efficacy claims derived from preclinical models. In this chapter, we argue that there are several existing examples that teach us on what needs to be done to improve the success rate. We advocate the reverse engineering approach that shifts the focus from preclinical efforts to "model" human disease states to pharmacodynamic activity as a common denominator in the journey to translate clinically validated phenomena to preclinical level and then back to humans. Combined with the research rigor, openness, and transparency, this reverse engineering approach is well set to bring new effective and safe medications to patients in need.