The Functional Anatomy, Neurochemistry, and Pharmacology of Anxiety

The functional anatomy of anxiety involves amygdala-based neurocircuits with critical reciprocal connections to the medial prefrontal cortex. Traumatic experiences leave emotional imprints involving the amygdala, with facilitated fear-conditioned associations involving declarative memory traces. Avoidance conditioning is an additional component. An understanding of the functional anatomy of anxiety allows for a new perspective on the various anxiety disorders. The neurotransmitters involved in these circuits are reviewed for their relevance to the pharmacologic choices in the treatment of anxiety. Potent serotonin reuptake inhibitors appear to have superior efficacy in many of the anxiety disorders, with indications that norepinephrine reuptake inhibitors have an advantage in severe forms of major depression. Medications with dual effects—blocking reuptake of both serotonin and norepinephrine (e.g., clomipramine and venlafaxine XR)—have superior benefits in achieving remission in major depression and GAD. These medications may also offer a faster onset of action and theoretically superior benefits in patients with comorbid anxiety disorder and major depression.