Fremanezumab Shows Dual Efficacy in Treating Migraine and Comorbid Major Depressive Disorder: JAMA
Researchers have found in a new study that Fremanezumab proved effective in reducing symptoms of both migraine and comorbid major depressive disorder in patients suffering from both conditions. The study was conducted by Richard B. L. and fellow researchers published in JAMA Neurology. Although migraine and major depressive disorder (MDD) frequently co-occur, evidence for effective treatment approaches for both conditions at the same time has been sparse. The UNITE study bridges this gap by evaluating fremanezumab, a calcitonin gene–related peptide (CGRP) monoclonal antibody indicated for migraine prevention in a patient population with both migraine (episodic or chronic) and MDD with active symptoms.
The UNITE trial was a double-blind, placebo-controlled, parallel-group trial from July 9, 2020, to August 31, 2022, at 55 centers in 12 countries. The trial consisted of a 4-week screening period, a 12-week double-blind treatment period, and a 12-week open-label extension (OLE).
540 adults were screened, of whom 353 patients were enrolled and randomized: 175 to fremanezumab (225 mg per month), and 178 to placebo. Participants were eligible if they had episodic migraine (48%) or chronic migraine (52%), along with a DSM-5-diagnosis major depressive disorder for ≥12 months, and a score of active depressive symptoms (PHQ-9 ≥10) at screening. For the OLE phase, all patients received quarterly fremanezumab (675 mg).
Key Findings
• The study population mean age was 42.9 years, and 88% (310/353) of the participants were female.
• Fremanezumab led to a mean decrease of −5.1 monthly migraine days (SE 0.50; 95% CI: −6.09 to −4.13) versus −2.9 days with placebo (SE 0.49; 95% CI: −3.89 to −1.96), a statistically significant difference (P <.001).
• At week 8, mean change from baseline in Hamilton Depression Rating Scale–17 Items score was −6.0 points (SE 0.55) with fremanezumab and −4.6 points (SE 0.54) with placebo. The between-group difference was −1.4 points (SE 0.61; 95% CI: −2.61 to −0.22; P = .02).
• The therapeutic effects of fremanezumab were sustained during the open-label extension period.
• Adverse events seen were as expected with prior fremanezumab trials, with no new safety issues identified in the study.
The UNITE study offers strong evidence that fremanezumab substantially decreases monthly migraine days and depressive symptoms in patients with both migraine and major depressive disorder, with no new safety issues. This dual effect represents a breakthrough in the treatment of comorbid neurological and psychiatric disorders, highlighting the promise of CGRP-targeting treatments such as fremanezumab in more integrated patient care approaches.
Reference:
Lipton RB, Ramirez Campos V, Roth-Ben Arie Z, et al. Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder: The UNITE Randomized Clinical Trial. JAMA Neurol. Published online May 05, 2025. doi:10.1001/jamaneurol.2025.0806
