Lipton Richard B, Ramirez Campos Verena, Roth-Ben Arie Zipi, Galic Maja, Mitsikostas Dimos, Tassorelli Cristina, Denysenko Lex, Cohen Joshua M
Departments of Neurology, Psychiatry and Behavioral Sciences, and the Montefiore Headache Center, Albert Einstein College of Medicine, New York, New York.
Teva Branded Pharmaceutical Products R&D Inc, West Chester, Pennsylvania.
JAMA Neurol. 2025 May 5. doi: 10.1001/jamaneurol.2025.0806.
Migraine and major depressive disorder are frequently comorbid; however, evidence evaluating the efficacy of preventive migraine therapy in patients with both diseases is limited.
To evaluate the efficacy and safety of fremanezumab in adults with migraine and comorbid major depressive disorder.
DESIGN, SETTING, AND PARTICIPANTS: The UNITE study was a double-blind, placebo-controlled, parallel-group, randomized clinical trial consisting of a 4-week screening period, 12-week double-blind period, and 12-week open-label extension (OLE), conducted between July 9, 2020, and August 31, 2022. The trial was conducted at 55 centers across 12 countries. Eligible patients were adults with episodic migraine (EM) or chronic migraine (CM), history of major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for 12 or more months before screening, and active symptoms of depression (9-item Patient Health Questionnaire score of 10 or more) at screening.
Patients were randomized 1:1 to receive monthly fremanezumab (225 mg) or matched placebo. All patients in the OLE received quarterly fremanezumab (675 mg).
The primary end point was the mean change from baseline in monthly migraine days during the 12-week double-blind period.
Of the 540 patients screened for the study, 353 patients (mean [SD] age, 42.9 [12.3] years; 310 female [88%]; EM, 48%; CM, 52%) were eligible and randomized to receive fremanezumab (n = 175) or placebo (n = 178). Mean (SE) change from baseline in monthly migraine days during the 12-week double-blind period was -5.1 (0.50; 95% CI, -6.09 to -4.13) for fremanezumab and -2.9 (0.49; 95% CI, -3.89 to -1.96) for placebo (P <.001). Mean (SE) change from baseline in the Hamilton Depression Rating Scale-17 Items score at week 8 was -6.0 (0.55; 95% CI, -7.10 to -4.95) for fremanezumab and -4.6 (0.54; 95% CI, -5.66 to -3.55) for placebo (least squares mean [SE] difference: -1.4 [0.61]; 95% CI, -2.61 to -0.22; P = .02). Adverse events were consistent with other fremanezumab trials. Results were maintained throughout the OLE.
Treatment with fremanezumab compared with placebo resulted in significant reductions in monthly migraine days and depressive symptoms. No new safety concerns were observed. To the authors' knowledge, this was the first placebo-controlled, randomized clinical trial, specifically designed to assess patients with migraine and comorbid depressive disorder, to demonstrate significant improvements in migraine and depressive symptoms with a single pharmacological intervention.
ClinicalTrials.gov Identifier: NCT04041284.
偏头痛与重度抑郁症常合并存在；然而，评估预防性偏头痛治疗对这两种疾病患者疗效的证据有限。
评估fremanezumab对伴有重度抑郁症的偏头痛成年患者的疗效和安全性。
设计、地点和参与者：UNITE研究是一项双盲、安慰剂对照、平行组随机临床试验，包括4周的筛查期、12周的双盲期和12周的开放标签延长期（OLE），于2020年7月9日至2022年8月31日进行。该试验在12个国家的55个中心开展。符合条件的患者为患有发作性偏头痛（EM）或慢性偏头痛（CM）的成年人，根据《精神疾病诊断与统计手册》（第五版）标准，在筛查前12个月或更长时间有重度抑郁症病史，且在筛查时有抑郁的活跃症状（9项患者健康问卷评分10分或更高）。
患者按1:1随机分组，接受每月一次的fremanezumab（225毫克）或匹配的安慰剂。OLE中的所有患者每季度接受一次fremanezumab（675毫克）。
主要终点是12周双盲期内每月偏头痛天数相对于基线的平均变化。
在筛查的540例患者中，353例患者（平均[标准差]年龄，42.9[12.3]岁；310例女性[88%]；EM，48%；CM，52%）符合条件并被随机分配接受fremanezumab（n = 175）或安慰剂（n = 178）。在12周双盲期内，fremanezumab组每月偏头痛天数相对于基线的平均（标准误）变化为-5.1（0.50；95%置信区间，-6.09至-4.13），安慰剂组为-2.9（0.49；95%置信区间，-3.89至-1.96）（P <.001）。在第8周时，fremanezumab组汉密尔顿抑郁量表17项评分相对于基线的平均（标准误）变化为-6.（0.55；95%置信区间，-7.10至-4.95），安慰剂组为-4.6（0.54；95%置信区间，-5.66至-3.55）（最小二乘均值[标准误]差异：-1.4[0.61]；95%置信区间，-2.61至-0.22；P = 0.02）。不良事件与其他fremanezumab试验一致。在整个OLE期间结果保持不变。
与安慰剂相比，fremanezumab治疗可显著减少每月偏头痛天数和抑郁症状。未观察到新的安全问题。据作者所知，这是第一项专门设计用于评估偏头痛合并抑郁症患者的安慰剂对照随机临床试验，证明单一药物干预可显著改善偏头痛和抑郁症状。
ClinicalTrials.gov标识符：NCT04041284。
