Future Drugs for the Treatment of Depression: The Need to Look Beyond Monoamine Systems

Abstract

Review of extant biological data would suggest that major depressive disorder (MDD) is a term used to subsume a syndrome that may involve a variety of different pathophysiological processes. Current research has implicated a myriad of different factors in the pathogenesis of depressive disorders including: genetic predisposition, “hormonal” abnormalities, disturbances in neurostransmitters, disturbances in neurocircuitry, and immune dysfunction. Our most recent consensus suggests that the depressive disorders reflect the interplay between these biological systems and psychosocial experiences, such as early-life trauma and current life stressors. Thus, MDD truly represents a complex heterogeneous syndrome. This conceptualization suggests that a variety of different types of treatment approaches will be necessary to adequately ameliorate the symptoms of patients suffering from this syndrome. Although this is a daunting task, we are beginning to develop approaches that will enable us to add to our armamentation of biological treatments.