Functional Brain Imaging and Drug Development

Abstract

The development of drugs for psychiatric diseases is a specially risky business, for several reasons: first, the etiology of most psychiatric diseases is unknown; second, most psychiatric diseases are exclusively human; and third, animal models are often limited or nonexistent. Usually large multicentric clinical trials are required to demonstrate clinical efficacy of a drug, with large investments and time needed. Functional brain imaging may help to decrease both time and investment in this process, thus becoming a useful tool for pharmaceutical companies. PET and SPECT are unique tools for the study of neurotransmission in humans in vivo, and allow direct assessment of the drug-target interactions at the synaptic level. Cerebral perfusion and metabolism imaging can indirectly contribute to drug development by allowing investigation of pathophysiology or the anatomical pathways implicated in psychiatric diseases and identification of the cerebral areas whose activity is modified as a consequence of drug administration. Functional brain imaging can be useful from very early stages of drug development, such as target identification. Furthermore, these techniques provide essential information on the pharmacokinetics and pharmacodynamics of the drug in the brain, contributing to the demonstration of the mechanism of action of the drugs and to the drug dosage. Small animal imaging systems are an additional tool, which together with neuroimaging of genetic expression in the future will help to complete the picture of functional brain imaging applications to drug development in Psychiatry.