Toward a Comprehensive Model of Depression: Implications for Antidepressant Over-prescription

Abstract

Depression is an etiologically complex and heterogeneous disorder. This review attempts to unite a large body of literature into a comprehensive model of pathology by integrating cognitive and behavioral approaches with neurobiological processes. Psychosocial stress induces pathological hypothalamic-pituitary-adrenal (HPA) axis and inflammatory activity, which in turn reduce circulating monoamine concentrations. These mechanisms have detrimental effects on neuron survival, growth, and proliferation. This model is also used to examine current issues in treatment, namely, concerns about an antidepressant over-prescription problem. It provides indirect, conceptual support for these concerns: unlike psychotherapy, antidepressants or other pharmaceutical drugs do not treat the psychosocial stress variable, which is central aspect of pathology. Consequently there is an important role for integrating multiple therapeutic approaches that target the heterogeneous pathways involved in depression.