Galcanezumab, an anti-CGRP peptide antibody for migraine, significantly reduced depression and anxiety scores in Japanese patients, and these improvements appeared independent of migraine frequency reduction.
Mood improvement independent of migraine reductionPHQ-9 and GAD-7 scores improved significantly, but these changes did not correlate with how many fewer migraine days patients had
What the researchers found
Monthly migraine days decreased significantly from 13.6 to 8.5 (p<0.001) during galcanezumab treatment. Depression scores (PHQ-9) dropped from 5.8 to 4.5 (p=0.010) and anxiety scores (GAD-7) from 4.0 to 3.1 (p=0.030).
Critically, no significant correlation was found between changes in depression/anxiety scores and changes in monthly migraine days, pain severity (NRS), or associated migraine symptoms. Fisher's exact tests also showed no significant association between PHQ-9/GAD-7 improvements and migraine frequency reduction. This suggests galcanezumab may have direct mood-modulating effects independent of its migraine-reducing action.
Why it matters
Depression and anxiety significantly worsen quality of life for migraine sufferers, yet they are often treated as separate conditions. If CGRP-blocking peptide therapies directly improve mental health — not just as a side effect of fewer headaches — it would fundamentally change how clinicians think about these drugs. CGRP may play a broader role in mood regulation than previously recognized.
How the study worked
Single-center, retrospective, real-world study at Keio University Hospital in Japan. 27 migraine patients treated with galcanezumab were assessed using validated depression (PHQ-9) and anxiety (GAD-7) questionnaires at baseline and 3-5 months after starting treatment. Correlation analyses examined whether mood improvements were linked to migraine improvement metrics.
What this study cannot tell us
Very small sample size (27 patients) limits statistical power and generalizability. The retrospective, single-center design without a control group means improvements could reflect placebo effects, natural fluctuation, or other factors. The 3-5 month follow-up is relatively short. Baseline depression and anxiety scores were relatively mild (below clinical thresholds for disorder), so the clinical significance of the improvements is debatable. The study was conducted only in Japanese patients, limiting cross-population generalizability.
How to read the evidence
This is a small (n=27), single-center, retrospective, real-world study without a control group. While the findings are intriguing, the evidence level is low due to the small sample, lack of control, and mild baseline symptom severity. Larger controlled studies are needed to confirm the independent mood effects.
When this study was published
Published in 2025, this is a recent study contributing to the emerging understanding of CGRP's role beyond headache in migraine patients.
The bigger picture
CGRP has been studied primarily as a pain signaling peptide, but emerging evidence suggests it plays roles in mood regulation and stress response. This study adds to a growing body of research suggesting that anti-CGRP therapies may have psychiatric benefits beyond their anti-migraine effects. If confirmed in larger trials, this could expand the therapeutic rationale for CGRP-targeting peptide drugs.
Questions still open
- Does CGRP peptide signaling directly influence brain circuits involved in depression and anxiety?
- Would anti-CGRP therapies show greater mental health benefits in migraine patients with more severe depression or anxiety?
- Do other anti-CGRP drugs (erenumab, fremanezumab) show similar mood-improving effects, suggesting a class effect?
Common questions
Can migraine medications help with depression and anxiety too?
What is galcanezumab and how does it work?
Read the original research
Effect of Galcanezumab on PHQ-9 and GAD-7 in Patients with Migraine: A Real-world Study in Japan.
Internal medicine (Tokyo, Japan)
Citation
Oshima, Kota; Hattori, Yuna; Ihara, Keiko; Watanabe, Narumi; Takemura, Ryo; Ishizuchi, Kei; Takahashi, Nobuyuki; Sekiguchi, Koji; Nakahara, Jin; Takizawa, Tsubasa. (2025). Effect of Galcanezumab on PHQ-9 and GAD-7 in Patients with Migraine: A Real-world Study in Japan.. Internal medicine (Tokyo, Japan). https://doi.org/10.2169/internalmedicine.5856-25