A recent clinical trial, known as the phase IV UNITE trial, demonstrated that fremanezumab (Ajovy) effectively reduced both migraine attacks and depression symptoms in individuals suffering from episodic or chronic migraines alongside major depressive disorder. The study involved 353 adults, with results showing that participants receiving fremanezumab experienced an average reduction of 5.1 migraine days per month compared to a 2.9-day reduction for those on placebo, a statistically significant difference (P<0.001).
The Hamilton Depression Rating Scale-17 Items (HAM-D 17) scores, which measure depression severity, also showed improvement. At the 8-week mark, those on fremanezumab had an average reduction of 6.0 points from baseline, while the placebo group saw a decrease of 4.6 points. The difference in HAM-D 17 scores at week 8 was 1.4 points in favor of fremanezumab (P=0.02). This scale ranges from 0 to 52, indicating that higher scores correspond to more severe depression.
Fremanezumab works by selectively targeting calcitonin gene-related peptide (CGRP), which plays a role in the development of migraines. The findings of this trial are noteworthy because they show a significant reduction in depression symptoms without the drug needing to penetrate the central nervous system effectively. According to Dr. Richard Lipton from the Albert Einstein College of Medicine, this outcome is particularly interesting as most treatments for depression usually involve medications that do penetrate the brain.
Previous studies indicated a link between migraines and depression, with many individuals experiencing both conditions simultaneously. The HALO CM trial also supported these findings, showing that fremanezumab could reduce headaches in patients with chronic migraine and depression. In another study, treatment targeting CGRP was associated with improvements in depressive symptoms, independent of migraine reductions.
Dr. Elizabeth Loder from Brigham and Women’s Hospital noted the importance of the UNITE trial, stating it provides valuable data on migraine treatment outcomes in patients with comorbid depression. She remarked that the treatment outcomes for those with depression appear to align with those seen in non-depressed migraine patients, which is reassuring. The trial results emphasize how frequent migraines can negatively impact mood disorders.
The trial’s design included a 4-week screening phase, a 12-week double-blind treatment period, and a 12-week open-label extension, where all participants received fremanezumab. The mean age of participants was 43 years, with 88% being female and 97% white. Nearly half had episodic migraines, while the other half experienced chronic migraines. A vast majority (98%) of participants were on additional medications during the trial, with 76% having previously used treatments for depression.
Overall, the UNITE trial suggests that fremanezumab not only decreases migraine frequency but also improves depressive symptoms in affected individuals. While improvements in depression were noted in both the fremanezumab and placebo groups, the study did not measure depressive symptoms weekly, leaving it unclear whether the reduction in migraine days preceded or followed the decline in depression.
The study was funded by Teva Pharmaceuticals, and Dr. Lipton disclosed relationships with various pharmaceutical companies, which may include potential conflicts of interest. The findings appear in JAMA Neurology, highlighting the importance of ongoing research in the intersection of migraine and mental health.
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