de Sousa Rafael T, Zanetti Marcus V, Brunoni Andre R, Machado-Vieira Rodrigo
Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of Sao Paulo, Brazil, Address: Instituto de Psiquiatria do HC-FMUSP, 3o andar, LIM-27, Rua Dr. Ovidio Pires de Campos, 785, Postal code 05403- 010, Sao Paulo, SP, Brazil.
Curr Neuropharmacol. 2015;13(5):616-35. doi: 10.2174/1570159x13666150630173522.
Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords "treatment-resistant depression", "major depressive disorder", "adjunctive", "refractory" and "augmentation". From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.
重度抑郁症（MDD）给社会带来了巨大负担和成本。在首次进行抗抑郁药物试验后，仅有三分之一的MDD患者实现了抑郁症状缓解，治疗失败在很大程度上导致了MDD患者所遭受的痛苦以及社会成本。本文总结了针对难治性抑郁症（TRD）已进行测试的治疗策略。使用关键词“难治性抑郁症”“重度抑郁症”“辅助治疗”“难治性”和“增效治疗”，对1975年至2014年9月的MedLine/PubMed数据库进行了计算机检索。从检索到的581篇文章中，两位作者筛选出79篇论文。通过手动检索进一步考虑了参考文献列表中的相关文章。研究发现的证据支持，在初始抗抑郁药物试验失败后，对于更严重的MDD，添加或换用另一类不同的抗抑郁药物是一种有效的策略。此外，对于对两类或更多类抗抑郁药物耐药的患者，应考虑一些增效策略和抗抑郁药物联合使用，尽管总体缓解率和治愈率相对较低，但速效谷氨酸能调节剂除外。TRD可用治疗方法的广泛反映了MDD的复杂性，而这并非该疾病各种关键特征的基础。有必要开展规模更大且设计良好的研究，采用维度方法来衡量疗效和有效性。
