Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Butler Hospital, Providence, RI 02906, USA.
Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
Treatment-resistant depression (TRD) is common and debilitating. Initial treatment is often insufficient to achieve full remission in a given depressive episode, resulting in more frequent episodes, worsened severity, and major disability.
This review surveys literature on the diagnosis and pharmacological management of TRD in light of recent developments. Evidence regarding commonly used treatment options is critically examined and key recommendations are offered. The review ends by considering drugs acting on the melatonin, acetylcholine, and glutamate systems that hold promise as future options for TRD.
Recent trends and research findings have impacted how the evidence supporting different approaches to TRD should be evaluated. For example, many earlier TRD studies employed tricyclics as the primary antidepressant, but tricyclics have now been superseded by selective serotonin reuptake inhibitors (SSRIs) in routine clinical practice. This deficiency has been addressed by the Sequenced Treatment Alternatives to Relieve Depression (STARD) study, the largest effectiveness study of TRD ever conducted. However, design characteristics of the STARD study preclude simple comparisons with earlier studies.
A shortcoming of most treatment recommendations for TRD is their reliance on older studies that do not reflect the current preeminence of SSRIs in clinical practice. This has distorted the prioritization of pharmacological strategies for TRD. Efforts to correct this distortion with effectiveness research, designed to better reflect current practice trends, require critical consideration of the strengths and limitations of this approach.
治疗抵抗性抑郁症（TRD）很常见且使人虚弱。在给定的抑郁发作中，初始治疗通常不足以实现完全缓解，从而导致发作更频繁、严重程度恶化和主要残疾。
根据最近的发展，本篇综述调查了 TRD 的诊断和药物治疗方面的文献。对常用治疗方法的证据进行了批判性检查，并提出了关键建议。综述最后还考虑了作用于褪黑素、乙酰胆碱和谷氨酸系统的药物，这些药物有望成为 TRD 的未来选择。
最近的趋势和研究发现影响了如何评估不同 TRD 方法的证据。例如，许多早期的 TRD 研究使用三环类抗抑郁药作为主要的抗抑郁药，但三环类抗抑郁药现在已被选择性 5-羟色胺再摄取抑制剂（SSRIs）在常规临床实践中取代。这一不足已通过缓解抑郁的序贯治疗选择（STARD）研究得到解决，这是有史以来对 TRD 进行的最大效果研究。然而，STARD 研究的设计特点使得与早期研究进行简单比较变得不可能。
TRD 的大多数治疗建议的一个缺点是它们依赖于不能反映 SSRIs 在临床实践中当前卓越地位的旧研究。这扭曲了 TRD 的药物治疗策略的优先级。通过旨在更好地反映当前实践趋势的有效性研究来纠正这种扭曲，需要对这种方法的优势和局限性进行批判性考虑。
