Meltzer-Brody Samantha, Gerbasi Margaret E, Mak Catherine, Toubouti Youssef, Smith Sarah, Roskell Neil, Tan Robin, Chen Shih-Yin Sharon, Deligiannidis Kristina M
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Sage Therapeutics, Inc., Cambridge, MA, USA.
J Med Econ. 2024 Jan-Dec;27(1):582-595. doi: 10.1080/13696998.2024.2334160. Epub 2024 Apr 15.
Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States.
Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18).
Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible.
Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results.
Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.
评估一种新型口服药物——唑奈诺龙（已获美国食品药品监督管理局批准用于治疗成人产后抑郁症）相对于选择性5-羟色胺再摄取抑制剂（SSRIs）以及美国用于产后抑郁症的联合疗法的相对疗效。
从系统评价中确定的唑奈诺龙和SSRIs的随机对照试验（RCTs）被用于构建证据网络，连接共同的对照臂。由于安慰剂反应存在异质性，采用匹配调整间接比较（MAIC），将3期云雀研究（NCT04442503）中唑奈诺龙治疗组在统计学上加权至研究产后抑郁症的SSRIs的RCTs的安慰剂组。MAIC输出结果应用于布彻间接治疗比较（ITCs）和网络荟萃分析（NMA），使用爱丁堡产后抑郁量表（EPDS）以及汉密尔顿抑郁量表17项版本（HAMD-17）从基线（CFB）起在第3天、15天、28天（第1个月）、45天和最后一次观察（第45天，第12/18周）的变化。
从第15天起，与接受SSRIs治疗的患者相比，接受唑奈诺龙治疗的患者的EPDS CFB更大。在第15天，接受唑奈诺龙治疗的（与接受SSRIs治疗的）患者的EPDS降低幅度大4.22分（95%置信区间：-6.16，-2.28），在第45天降低幅度大7.43分（-9.84，-5.02）（布彻ITC）。NMA显示，到第15天，唑奈诺龙使EPDS降低的幅度比SSRIs大4.52（-6.40，-2.65）分，在第45天大7.16（-9.47，-4.85）分。研究人群之间缺乏重叠显著降低了匹配后的有效样本量，使得HAMD-17 CFB分析不可行。
云雀研究与RCTs之间的人群重叠有限，降低了进行HAMD-17 CFB ITCs的可行性，并可能给EPDS CFB ITC结果带来不确定性。
分析表明，从第15天起，接受唑奈诺龙治疗的产后抑郁症患者比接受SSRIs治疗的患者症状改善更明显，在第45天平均差异最大。调整安慰剂组之间的差异后，与SSRIs相比，唑奈诺龙可能与产后抑郁症症状改善更大（以EPDS衡量）相关。
