Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder: The UNITE Randomized Clinical Trial

Abstract

Importance: Migraine and major depressive disorder are frequently comorbid; however, evidence evaluating the efficacy of preventive migraine therapy in patients with both diseases is limited. Objective: 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. Interventions: Patients were randomized 1:1 to receive monthly fremanezumab (225 mg) or matched placebo. All patients in the OLE received quarterly fremanezumab (675 mg). Main Outcomes and Measures: The primary end point was the mean change from baseline in monthly migraine days during the 12-week double-blind period. Results: 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