Mann J John, Rizk Mina M
Department of Psychiatry, Columbia University Irving Medical Center, Columbia University, New York, NY, USA.
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA.
Expert Rev Neurother. 2023 Apr;23(4):331-363. doi: 10.1080/14737175.2023.2190886. Epub 2023 Apr 10.
Current treatment of major depressive disorder (MDD) warrants critical reexamination. Initial treatment response rates are modest and drop dramatically after 3 months. Meanwhile, MDD is emerging as the leading cause of disease burden worldwide.
We searched PubMed (up to June 2021) for randomized controlled trials comparing antidepressant combinations versus monotherapy. We discuss findings from these studies in light of current treatment guidelines for MDD. These recommend a sequence of single, six-week-long, medication trials, before trying antidepressant combinations. The result leaves one third of patients still depressed after six months of treatment.
Optimizing the first three months of MDD treatment is crucial because response rates during this period are five times better than in the second three months. We propose a new, evidence-based algorithm of sequential antidepressant treatment steps, termed Accelerated Sequential Antidepressant Protocol (ASAP), that may offer better response rates than current guidelines. ASAP involves shorter duration medication trials (2-4 weeks) and earlier use of antidepressant combinations, seeking additive antidepressant effects without worsening side effects. Future research should compare ASAP to current treatment guidelines. Research is also needed on the role of rapidly acting antidepressants like ketamine for acutely ill and suicidal depressed patients.
当前对重度抑郁症（MDD）的治疗值得进行批判性重新审视。初始治疗反应率一般，且3个月后会大幅下降。与此同时，MDD正成为全球疾病负担的主要原因。
我们检索了PubMed（截至2021年6月），以查找比较抗抑郁药联合治疗与单一疗法的随机对照试验。我们根据当前MDD的治疗指南讨论这些研究的结果。这些指南建议在尝试抗抑郁药联合治疗之前，先进行一系列为期六周的单一药物试验。结果是，三分之一的患者在治疗六个月后仍处于抑郁状态。
优化MDD治疗的前三个月至关重要，因为在此期间的反应率比后三个月高出五倍。我们提出了一种新的、基于证据的序贯抗抑郁治疗步骤算法，称为加速序贯抗抑郁方案（ASAP），该方案可能比当前指南提供更好的反应率。ASAP包括持续时间更短的药物试验（2 - 4周）以及更早使用抗抑郁药联合治疗，以寻求相加的抗抑郁效果而不加重副作用。未来的研究应将ASAP与当前治疗指南进行比较。对于像氯胺酮这样的速效抗抑郁药在急性病和有自杀倾向的抑郁症患者中的作用，也需要进行研究。
