Jha Manish K, Mathew Sanjay J
Center for Depression Research and Clinical Care, Department of Psychiatry, UT Southwestern Medical Center, and O'Donnell Brain Institute, UT Southwestern Medical Center, Dallas (Jha); Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston (Mathew); Michael E. DeBakey VA Medical Center, Houston (Mathew); Menninger Clinic, Houston (Mathew).
Am J Psychiatry. 2023 Mar 1;180(3):190-199. doi: 10.1176/appi.ajp.20230025.
One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.
三分之一患有重度抑郁症（MDD）的成年人在接受多个连续疗程的抗抑郁药治疗后，并未出现具有临床意义的改善，从而患有难治性抑郁症（TRD）。TRD的存在导致了与MDD相关的发病率和额外死亡率，并与医疗费用的显著增加有关。由于缺乏对TRD的共识定义，本报告采取了一种宽泛的方法，考虑对一个或多个疗程抗抑郁药反应不足的情况，并重点关注美国食品药品监督管理局批准用于治疗抑郁症的非典型抗精神病药物（阿立哌唑、布雷哌唑、卡立普嗪、缓释喹硫平以及奥氮平-氟西汀组合）。虽然多项急性期研究已证明这些药物在改善抑郁症状方面的疗效，但具有临床意义的改善（即缓解）仍然有限，且对副作用（包括体重增加、代谢功能障碍、锥体外系症状和迟发性运动障碍）存在重大担忧，尤其是长期使用时。在过去几年中，抗抑郁治疗领域迅速发展，快速起效的抗抑郁药（如艾氯胺酮鼻喷雾剂和右美沙芬-安非他酮组合）已获批准，还有几种药物处于后期研发阶段（如祖拉诺酮和裸盖菇素），非典型抗精神病药物的使用是否会步那些使用较少的老式抗抑郁药（如三环类药物和单胺氧化酶抑制剂）的后尘，仍有待观察。需要进行务实的临床试验，以比较非典型抗精神病药物与针对TRD的药物疗法和神经调节治疗的有效性，并确定这些不同方法对MDD患者的最佳使用顺序。在使用非典型抗精神病药物时，鼓励临床医生和患者采用共同决策的方法，根据预期的副作用、耐受性、成本和可行性来个性化选择治疗方案。
