Duke-National University of Singapore, Singapore, Singapore.
Department of Psychiatry, Texas Tech University Health Sciences Center, Odessa, Texas, USA.
J Clin Psychiatry. 2020 Aug 11;81(5):19m12949. doi: 10.4088/JCP.19m12949.
An antidepressant medication switch often follows a failed initial trial with selective serotonin reuptake inhibitors (SSRIs). When, for whom, and how often second-step response and remission occur are unclear, as is preferred second-step trial duration. As more treatments are approved for use following 2 failed "adequate" trials, researchers and clinicians require an evidence-based definition of "adequate."
Following citalopram in the randomized Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial (which ran July 2001-September 2006), participants with score ≥ 11 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR₁₆) were randomized to bupropion sustained release, sertraline, or venlafaxine extended release (up to 14 weeks). The QIDS-SR₁₆ defined response, remission, and no clinically meaningful benefit based on the modified intent-to-treat sample.
About 80% of 438 participants completed ≥ 6 weeks of treatment with the switch medication. All treatments had comparable outcomes. Overall, 21% (91/438) remitted, 9% (40/438) responded without remission, and 58% (255/438) had no meaningful benefit. Half of the responses and two-thirds of remissions occurred after 6 weeks of treatment. Overall, 33% of responses (43/131) occurred after ≥ 9 weeks of treatment. No baseline features differentiated early from later responders or remitters. No early triage point was found, but those with at least 20% reduction from baseline in QIDS-SR₁₆ score around week 2 were 6 times more likely to respond or remit than those without this reduction.
Following nonefficacy with an initial SSRI, only about 20% remit and more than half achieve no meaningful benefit with a second-step switch to another monoaminergic antidepressant. A 12-week trial duration seems necessary to capture as many second-step switch responders as possible.
ClinicalTrials.gov identifier: NCT00021528.
在选择性 5-羟色胺再摄取抑制剂（SSRIs）初始治疗失败后，通常会进行抗抑郁药物转换。目前尚不清楚第二步反应和缓解发生的时间、人群以及频率，也不清楚第二步试验的最佳持续时间。随着越来越多的治疗方法在两次“充分”试验失败后被批准使用，研究人员和临床医生需要一个基于证据的“充分”定义。
在随机序贯治疗选择缓解抑郁（STAR*D）临床试验（2001 年 7 月至 2006 年 9 月进行）中，西酞普兰治疗后，16 项快速抑郁症状自评量表-自我报告（QIDS-SR₁₆）评分≥11 的参与者被随机分配至安非他酮缓释片、舍曲林或文拉法辛缓释片（最长 14 周）。根据修改后的意向治疗样本，QIDS-SR₁₆ 定义了反应、缓解和无临床意义获益。
约 438 名参与者中的 80%完成了切换药物的治疗≥6 周。所有治疗的结果都相当。总体而言，21%（91/438）缓解，9%（40/438）有反应但未缓解，58%（255/438）无明显获益。约一半的反应和三分之二的缓解发生在治疗 6 周后。总体而言，33%的反应（43/131）发生在治疗≥9 周后。没有基线特征可以区分早期和晚期反应者或缓解者。没有发现早期分诊点，但那些在 QIDS-SR₁₆ 评分第 2 周左右基线降低至少 20%的患者，比没有这种降低的患者有 6 倍的可能性出现反应或缓解。
在初始 SSRIs 治疗无效后，只有约 20%的患者缓解，超过一半的患者在进行第二步切换至另一种单胺类抗抑郁药后无明显获益。12 周的试验持续时间似乎是尽可能多地捕获第二步切换反应者所必需的。
ClinicalTrials.gov 标识符：NCT00021528。
