Neuroscientific Understanding of the Mechanism of Action of SSRI in the Treatment of Anxiety Disorders

Abstract

In 1999, a selective serotonin reuptake inhibitor (SSRI) was introduced to the clinic in Japan. This introduction greatly improved the treatment of anxiety disorder and understanding of its pathology. Since SSRI with high selectivity and no other mechanism of action is effective for treating anxiety disorder, increasing extracellular serotonin concentrations in the brain is concluded to directly alleviate the symptoms of anxiety disorder. In addition, on the basis of the details of neural circuits of anxiety and fear, which have been elucidated since 1993, several animal studies have shown that the mechanism of anxiolytic action of SSRIs is suppressing the neural function of the amygdala and their action is mediated through the stimulation of the 5-HT_1A receptor. The hypotheses obtained from these animal experiments are also supported by human imaging studies using fMRI. By elucidating the mechanism of action of SSRI, it is expected that it will become possible in the future to understand the pathology of anxiety disorders and develop the new treatment of anxiety disorders from the viewpoints of neural circuits and neurotransmitters.