Trivedi Madhukar H
Depression and Anxiety Disorders Program, The University of Texas, Southwestern Medical School, Dallas, Texas, USA.
Ann Clin Psychiatry. 2003 Mar;15(1):59-70. doi: 10.1023/a:1023232727217.
Managing patients with treatment-resistant depression (TRD) remains a major challenge for the practicing physician. Depression is considered treatment-resistant when at least two adequate monotherapy trials with drugs from different pharmacologic classes fail to elicit a therapeutic response. Although determining the stage of TRD may allow concise description of a patient's antidepressant history, management of TRD is better served by recent attempts to create a treatment algorithm that encompasses definitive diagnosis of true TRD and strategies for optimizing available therapies, including consideration of novel treatment options. Present strategies for managing TRD include optimization of the initial drug, substitution of another drug from the same or a different antidepressant class, combination of two antidepressants with different mechanisms of action, and adding an antidepressant drug from another class. Potential nonpharmacologic treatments include vagus nerve stimulation, repetitive transcranial magnetic stimulation, and magnetic seizure therapy as an alternative to electroconvulsive therapy. Several neuropeptides and their receptors have also been identified as potential targets for pharmacologic intervention, including corticotropin-releasing factor and substance P. Other treatments currently under investigation include augmentation of antidepressant therapy with an atypical antipsychotic agent such as olanzapine or risperidone. This kind of therapeutic intervention may prove to be especially useful in treating patients with TRD.
对于执业医师而言，治疗难治性抑郁症（TRD）患者仍然是一项重大挑战。当使用来自不同药理类别的药物进行至少两次充分的单药治疗试验均未能引发治疗反应时，抑郁症即被视为难治性。尽管确定TRD的阶段可能有助于简洁描述患者的抗抑郁治疗史，但通过最近尝试创建一种治疗算法来管理TRD会更有帮助，该算法涵盖对真正TRD的明确诊断以及优化现有疗法的策略，包括考虑新的治疗选择。目前管理TRD的策略包括优化初始药物、用同一类或另一类抗抑郁药替代、联合使用两种作用机制不同的抗抑郁药以及添加另一类抗抑郁药。潜在的非药物治疗包括迷走神经刺激、重复经颅磁刺激以及作为电休克治疗替代方法的磁惊厥治疗。几种神经肽及其受体也已被确定为药物干预的潜在靶点，包括促肾上腺皮质激素释放因子和P物质。目前正在研究的其他治疗方法包括用奥氮平或利培酮等非典型抗精神病药物增强抗抑郁治疗。这种治疗干预可能在治疗TRD患者方面特别有用。
