Computational methods for the discovery of mood disorder therapies

Despite the significant progress, research is still needed to reveal details of the complex and dynamic chemical processes operating in the central nervous system (CNS) and their relationship to psychological effects such as mood disorders. The incidence of behavioral depression is widely spread worldwide, with an estimated 14.8 million adults diagnosed yearly in the United States alone. The efficacy of current antidepressants on 50 - 60% of patients, their slow onset of action and the prevalence of adverse side effects highlight the need for developing a new generation of improved antidepressants. Computational methods have the potential to aid in the discovery of mood modulators.

This review contains three main sections: historical evolution of marketed antidepressants, physicochemical and structural properties of antidepressant compounds reported in the ChEMBL database and recent efforts in the design and discovery of antidepressants using computational methods. The authors provide details of the computational methods employed, from chemoinformatic analyses to molecular modeling.

While there have been numerous and important findings in depression research, the high cost and time spent on research into new therapies for brain disorders is a risky undertaking. Computational methodologies can be employed to speed up the discovery of new antidepressants and to detect new sources of chemical compounds with potential antidepressant activity. Compound collections containing compounds already approved in the pharmaceutical and food industries that cover the property space and complement the structural space of CNS drugs represent a promising starting point for the discovery of new antidepressant agents.