Overview of different pharmacotherapies for attaining remission in generalized anxiety disorder.

γ-Aminobutyric acid (GABA), serotonin (5-HT), and norepinephrine (NE) have each been implicated in the putative pathophysiology of anxiety, and patients with generalized anxiety disorder (GAD) demonstrate dysregulation of these neurotransmitters. In addition, neurobiological studies have demonstrated that these neurotransmitter systems are extensively interrelated. As a result, drugs that affect serotonergic systems may also, directly or indirectly, affect other neurotransmitter systems including GABA and NE. In recent years, clinical pharmacology studies have demonstrated that pharmacotherapeutic agents that target more than one neurotransmitter system are more effective than agents that target a single system, presumably due to synergistic mechanisms. Agents that modulate more than one neurochemical have a broader spectrum of action and may facilitate the attainment of remission among patients with moderate to severe GAD, who are likely to have comorbid psychiatric illnesses such as depression. Preclinical and clinical data supporting the role of GABA, 5-HT, and NE in the pathophysiology of GAD are reviewed here. The pharmacotherapeutic agents that modulate these neurotransmitter systems and have been proved efficacious in reducing the symptoms associated with GAD are also summarized.