a Department of Psychiatry and Behavioral Sciences , Duke University Medical Center , Durham , NC , USA.
b Department of Psychiatry , The Catholic University of Korea College of Medicine , Seoul , Republic of Korea.
Expert Rev Neurother. 2017 Aug;17(8):777-790. doi: 10.1080/14737175.2017.1341310. Epub 2017 Jun 19.
There are numerous antidepressants for the treatment of major depressive disorder (MDD) on the market. However, inadequate treatment response, therapeutic lag between drug administration and the onset of clinical improvement, and safety/tolerability issues with the use of contemporary antidepressants have accelerated the search for newer antidepressants with novel mechanisms of action. Areas covered: The authors review novel antidepressants with rapid efficacy for diverse MDD symptoms and have fewer adverse effects (AEs). Mechanisms of action for novel therapeutic molecules are through glutamatergic, opiate, cholinergic receptors and neuroplasticity. We enumerate results from human trials with novel agents in all phases, highlighting proximity to approval and therapeutic potential based on quality of evidence. Expert commentary: There is a huge unmet need to diversify conventional antidepressant targets. Glutamatergic and opiate agents may be most promising among newer therapeutic agents. It is also important to develop advanced but flexible synergistic treatment strategies with newer therapeutic agents that are usable in routine clinical practice. This would include combining newer molecules with existing antidepressants and using molecules that target specific symptom dimensions of MDD. These strategies would lead to a systematic approach to tackle treatment resistant depression (TRD) and treatment of residual symptoms in partially remitted MDD.
市场上有许多用于治疗重度抑郁症（MDD）的抗抑郁药。然而，治疗反应不足、药物治疗与临床改善开始之间的治疗滞后以及当代抗抑郁药的安全性/耐受性问题，加速了对具有新型作用机制的新型抗抑郁药的寻找。
作者回顾了具有快速疗效的新型抗抑郁药，这些药物对多种 MDD 症状的不良反应（AEs）较少。新型治疗分子的作用机制是通过谷氨酸能、阿片能、胆碱能受体和神经可塑性。我们列举了所有阶段新型药物的人体试验结果，根据证据质量突出了接近批准和治疗潜力。
多样化传统抗抑郁药靶点的需求巨大。谷氨酸能和阿片能药物可能是新型治疗药物中最有前途的。同样重要的是，要与新型治疗药物一起开发先进但灵活的协同治疗策略，这些药物可在常规临床实践中使用。这将包括将新型分子与现有抗抑郁药结合使用，并使用针对 MDD 特定症状维度的分子。这些策略将导致一种系统的方法来解决治疗抵抗性抑郁症（TRD）和部分缓解的 MDD 残留症状。
