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[Pharmacotherapy of anxiety disorders]

Takeshi Inoue
Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica 2012, 114 (9): 1085-92
23198599
Until the 1980s, benzodiazepines were first-line drugs used to treat anxiety disorders. However, benzodiazepines present some limitations: they are ineffective for some subtypes of anxiety disorders. Moreover, they entail side effects such as dependency, somnolence, and memory disturbances. Since 1980s, several clinical trials have shown that selective serotonin reuptake inhibitors (SSRIs), which have no dependency, are effective for most subtypes of anxiety disorders. Consequently, SSRIs are now anti-anxiety drugs as well as antidepressants. In a recent guideline for the pharmacological treatment of anxiety disorders developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force, SSRIs are first-line drugs for the treatment of most subtypes of anxiety disorders. However, SSRIs do not improve symptoms in all patients with anxiety disorders. Therefore, benzodiazepines and tricyclic antidepressants are used even now for the treatment of anxiety disorder. Furthermore, off-label pharmacotherapies, supportive and other psychotherapies, and psychoeducation are applied to the treatment of anxiety disorders. Pharmacotherapy is part of integrative therapy of anxiety disorders. The treatment and pathogenesis of treatment-resistant anxiety disorders have not been elucidated sufficiently. Future studies must be conducted to elucidate the pathogenesis and to develop a new treatment for treatment-resistant anxiety disorders. In contrast to those for other emotions, the neurocircuits related to anxiety and fear have been clarified in detail. The author and others have investigated the mechanisms and target brain regions of the anti-anxiety action of SSRIs using an animal model of anxiety: conditioned fear stress. Results show that SSRIs inhibit glutamatergic neurons of the amygdala through increased extracellular serotonin levels. This inhibition engenders anti-anxiety action. Benzodiazepines also inhibit the amygdala, thereby reducing fear or anxiety. The inhibitory action on the amygdala might be a common mechanism of anti-anxiety action of SSRIs and benzodiazepines.

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