Generalized anxiety disorder: neurobiological and pharmacotherapeutic perspectives.

The concept of generalized anxiety has evolved over many years, from initial descriptions of "anxiety neurosis" to recognition of generalized anxiety disorder (GAD) as a clinical entity included in the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. Since 1980, the definition of GAD has undergone further change, with modifications in the salience of autonomic and panic like symptoms, duration, and allowance of comorbidity. The importance of these historical considerations lies in the fact that most of our current knowledge about GAD rests on outdated definitions, including most of the literature pertaining to treatment. Indeed, we cannot be sure that the DSM-III definition of GAD bears resemblance to the current concept, and these differences may have profound implications for findings from research. The following two-part report comprises i) a review of the basic neurobiology of GAD, with reference to serotonergic, noradrenergic, neuroendocrine, autonomic imaging, and other systems; and ii) an overview of the current status of pharmacotherapy for GAD.