Fremanezumab Shows Promise for Migraine Plus Depression

Medscape

13-05-2025

Fremanezumab was associated with a significantly greater reduction in monthly migraine days and symptoms of depression than placebo in patients with migraine and comorbid major depressive disorder (MDD), new research showed.
METHODOLOGY:
UNITE, a double-blind, placebo-controlled, parallel-group randomized clinical trial, was conducted at 55 centers across 12 countries between 2020 and 2022. It consisted of a 4-week screening period, a 12-week double-blind period, and a 12-week open-label extension.
A total of 353 adult patients (mean age, 43 years; 88% women) with episodic migraine (48%) or chronic migraine (52%) and comorbid MDD for 12 months or more were randomly assigned to receive either 225 mg/mo fremanezumab (n = 175) or matching placebo (n = 178).
Active depression symptoms were assessed using the Hamilton Depression Rating Scale-17 items (HAM-D 17) and nine-item Patient Health Questionnaire.
Endpoints included mean changes from baseline in the average number of monthly migraine days at 12 weeks and in depressive symptom scores at 8 weeks.
TAKEAWAY:
At 12 weeks, 33% vs 13% of patients taking fremanezumab vs placebo achieved a ≥ 50% reduction in the number of monthly migraine days ( P < .001), with a mean reduction of 5.1 vs 2.9 days ( P < .001).
< .001), with a mean reduction of 5.1 vs 2.9 days ( < .001). HAM-D 17 scores at 8 weeks were significantly reduced in the fremanezumab group vs the placebo group (mean reduction in scores, 6.0 vs 4.6; P = .02).
= .02). In all, 40% of the fremanezumab group and 27% of the placebo group reported at least one adverse event of mostly mild or moderate severity at 12 weeks.
Improvements in both migraine and depressive symptoms were maintained even throughout the open-label extension.
IN PRACTICE:
'Recommendations have focused on treating patients with migraine and comorbidities with a single drug to address both, as this approach appears to simplify management, reduce costs, minimize potential AEs [adverse events], and eliminate potential drug interactions,' the investigators wrote.
However, 'Fremanezumab may provide an effective and well-tolerated preventive treatment option for this patient population,' they added.
SOURCE:
This study was led by Richard B. Lipton, MD, Albert Einstein College of Medicine, New York City. It was published online on May 5 in JAMA Neurology .
LIMITATIONS:
This study excluded patients with uncontrolled psychiatric or bipolar disorders, limiting its generalizability. Potential drug interactions with fremanezumab and unrecorded dose adjustments may have influenced the outcomes. Depression was not tracked weekly, preventing the analysis of the timing between improvements in migraine and mood. Additionally, the predominantly White study population limited the generalizability to more diverse groups.
DISCLOSURES:
Funding information was not provided for the study. Several investigators reported having financial or employment ties with various pharmaceutical companies, including the manufacturer of fremanezumab. Full details are provided in the original article.