What might the psychobiology of posttraumatic stress disorder teach us about future approaches to pharmacotherapy?

This review considers future directions for developing effective drugs for posttraumatic stress disorder (PTSD). At present, we have embarked upon an empirical approach in which pharmacologic research consists of clinical trials with agents, such as antidepressants, anxiolytics, and anticonvulsants, initially developed for different purposes. The approach taken here is theoretical rather than empirical, starting with what is known about the unique pathophysiology of PTSD and then predicting the types of pharmacologic agents that might prove effective in the future. Such classes of compounds include corticotropin-releasing factor antagonists, neuropeptide Y enhancers, antiadrenergic compounds, drugs to down-regulate glucocorticoid receptors, more specific serotonergic agents, agents normalizing opioid function, substance P antagonists, N-methyl-D-aspartate facilitators, and antikindling/antisensitization anticonvulsants.