UNITE
Trial question
What is the role of fremanezumab in patients with migraine and comorbid major depressive disorder?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
88.0% female
12.0% male
N = 353
353 patients (310 female, 43 male).
Inclusion criteria: adult patients with episodic or chronic migraine and comorbid major depressive disorder.
Key exclusion criteria: ≥ 4 failed different medication classes to treat depression; use of intervention or device for migraine or depression in the past 2 months; use of electroconvulsive therapy; constant or nearly constant headache; severe or uncontrolled psychiatric disorder; cancer; pregnancy.
Interventions
N=175 fremanezumab (225 mg monthly via subcutaneous injection).
N=178 placebo (matching subcutaneous placebo injection).
Primary outcome
Reduction in monthly migraine days during 12-week treatment period
5.1 days
2.9 days
5.1 days
3.8 days
2.5 days
1.3 days
0.0 days
Fremanezumab
Placebo
Significant
increase ▲
Significantly greater reduction in monthly migraine days during the 12-week treatment period (5.1 days vs. 2.9 days; LSMD 2.2, 95% CI 1.21 to 3.16).
Secondary outcomes
Significantly greater reduction in Hamilton Depression Rating Scale-17 items score at week 8 (6 points vs. 4.6 points; LSMD 1.4, 95% CI 0.22 to 2.61).
Significant increase in reduction by ≥ 50% in monthly migraine days during the 12-week treatment period (33% vs. 13%; OR 3.26, 95% CI 1.9 to 5.6).
Significantly lower reduction in Clinical Global Impression-Severity score at week 12 (1.1 points vs. 0.8 points; LSMD 0.4, 95% CI 0.12 to 0.58).
Safety outcomes
No significant difference in ≥ 1 severe and serious adverse events.
Conclusion
In adult patients with episodic or chronic migraine and comorbid major depressive disorder, fremanezumab was superior to placebo with respect to reduction in monthly migraine days during the 12-week treatment period.
Reference
Richard B Lipton, Verena Ramirez Campos, Zipi Roth-Ben Arie et al. Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder: The UNITE Randomized Clinical Trial. JAMA Neurol. 2025 May 5. Online ahead of print.
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