Inoue Takeshi
Department of Psychiatry, Hokkaido University Graduate School of Medicine.
Seishin Shinkeigaku Zasshi. 2012;114(9):1085-92.
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.
直到20世纪80年代，苯二氮䓬类药物都是用于治疗焦虑症的一线药物。然而，苯二氮䓬类药物存在一些局限性：它们对某些焦虑症亚型无效。此外，它们还会带来诸如依赖性、嗜睡和记忆障碍等副作用。自20世纪80年代以来，多项临床试验表明，无依赖性的选择性5-羟色胺再摄取抑制剂（SSRI）对大多数焦虑症亚型有效。因此，SSRI现在既是抗焦虑药物也是抗抑郁药物。在世界生物精神病学协会联合会（WFSBP）工作组制定的最近一份焦虑症药物治疗指南中，SSRI是治疗大多数焦虑症亚型的一线药物。然而，SSRI并不能改善所有焦虑症患者的症状。因此，即使在现在，苯二氮䓬类药物和三环类抗抑郁药仍被用于治疗焦虑症。此外，非标签药物疗法、支持性和其他心理疗法以及心理教育也被应用于焦虑症的治疗。药物治疗是焦虑症综合治疗的一部分。难治性焦虑症的治疗和发病机制尚未得到充分阐明。必须开展未来研究以阐明发病机制并开发难治性焦虑症的新治疗方法。与其他情绪相关的神经回路不同，与焦虑和恐惧相关的神经回路已得到详细阐明。作者等人使用焦虑动物模型：条件性恐惧应激，研究了SSRI抗焦虑作用的机制和目标脑区。结果表明，SSRI通过增加细胞外5-羟色胺水平来抑制杏仁核的谷氨酸能神经元。这种抑制产生抗焦虑作用。苯二氮䓬类药物也抑制杏仁核，从而减轻恐惧或焦虑。对杏仁核的抑制作用可能是SSRI和苯二氮䓬类药物抗焦虑作用的共同机制。
