Efficacy of Fremanezumab in Reducing Depression in Patients With Migraine and Major Depressive Disorder: Results of the UNITE Study

This study was funded by Teva Pharmaceuticals. Background and Aims: Depression is a prevalent comorbidity associated with migraine and the burden of both disorders can decrease quality of life. UNITE examined the efficacy of fremanezumab in reducing depression in patients with migraine and major depressive disorder (MDD). Methods: In this 12-week, double-blind, parallel-group study (NCT04041284), adults with migraine and MDD with active moderate-to-severe depression were randomized (1:1) to monthly fremanezumab (225 mg) or placebo. Patients in the 12-week open label extension (OLE) received quarterly fremanezumab (675 mg). Exclusion criteria: bipolar disorder, psychotic features, catatonia, or suicidality. One concomitant medication for depression was permitted if the dose was stable ≥8 weeks prior to screening, with no changes anticipated. Key endpoints: mean change from baseline in symptoms of depression measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) and Patient Health Questionnaire-9 (PHQ 9). Results: Among 353 patients randomized (mean age 42.9 years; 88% female), 330 completed the double-blind period. Mean change from baseline in HAMD-17 score was –6.0 versus –4.6 at Week 8 (P=0.0205), and –6.7 versus –5.4 at Week 12 (P=0.0228) for fremanezumab and placebo, respectively. Mean change from baseline in PHQ 9 score was –7.1 versus –5.8 at Week 8 (P=0.0283) and –7.8 versus –6.3 at Week 12 (P=0.0108) for fremanezumab and placebo, respectively. Reductions were maintained throughout the OLE. Conclusion: The statistically significant reduction in HAMD-17 scores, and clinically meaningful reductions in PHQ-9 scores, indicate that fremanezumab may reduce the symptoms and cumulative burden of migraine and depression.