Anti-CGRP migraine drugs unexpectedly improve restless legs syndrome symptoms in comorbid patients | Research

The takeaway

Three months of CGRP monoclonal antibody therapy significantly reduced RLS severity (IRLS -11.6 points), central sensitization, and migraine disability in 15 patients with comorbid migraine and restless legs syndrome, with 73% reporting RLS improvement.

RLS improved by CGRP drugs
Anti-CGRP monoclonal antibodies reduced restless legs syndrome severity by 11.6 points even in patients whose migraines did not respond—suggesting a direct CGRP-RLS connection

What the researchers found

≥50% MMD reduction: 53-67% across months. IRLS: -8.8 points (1 month), -11.6 points (3 months). MIDAS: 25.1→19.7 (p=0.005). CSI: 36.3→29.1 (p=0.001). PGIC RLS improvement: 73.3%. RLS improvement even in migraine non-responders: 66.6%.

Why it matters

RLS affects 5-10% of the population with limited treatment options. Finding that anti-CGRP drugs improve RLS—independently of migraine—suggests CGRP plays a role in RLS and could lead to a new treatment approach.

How the study worked

Retrospective study of 15 migraine+RLS patients on CGRP mAbs (2 erenumab, 3 galcanezumab, 10 fremanezumab). IRLS, MIDAS, CSI, PGIC at 1-3 months.

What this study cannot tell us

Very small (n=15). Retrospective. No control group. Predominantly female (93%). Three different CGRP mAbs used. Placebo effect cannot be excluded.

How to read the evidence

Small retrospective case series. Important serendipitous finding needing larger validation.

When this study was published

Published in 2025.

The bigger picture

This serendipitous finding connects two common neurological conditions through shared CGRP biology. If confirmed, anti-CGRP drugs could become dual-purpose treatments for migraine+RLS patients.

Questions still open

Does CGRP play a direct role in RLS pathophysiology?
Would anti-CGRP drugs work for RLS without comorbid migraine?
Is the RLS improvement from reduced central sensitization or a direct mechanism?

Common questions

Can migraine drugs treat restless legs syndrome?

This small study found that anti-CGRP migraine drugs significantly improved RLS symptoms in patients who had both conditions. RLS severity scores dropped by nearly 12 points, and 73% of patients reported improvement. The benefit was even seen in patients whose migraines did not fully respond.

What connects migraine and restless legs syndrome?

Both conditions involve abnormal neural excitability (central sensitization), and this study found anti-CGRP drugs reduced central sensitization scores alongside both migraine and RLS symptoms. CGRP may play a role in the heightened nervous system sensitivity underlying both conditions.

Read the original research

The effect of calcitonin gene-related peptide monoclonal antibodies on restless legs syndrome in patients with migraine.

The journal of headache and pain, 26(1), 36

View on PubMed ↗Publisher’s paper ↗

Citation

Suzuki, Keisuke; Suzuki, Shiho; Fujita, Hiroaki; Kobayashi, Saro; Shioda, Mukuto; Hida, Ryotaro; Hirata, Koichi. (2025). The effect of calcitonin gene-related peptide monoclonal antibodies on restless legs syndrome in patients with migraine.. The journal of headache and pain, 26(1), 36. https://doi.org/10.1186/s10194-025-01976-7