Non-Invasive Brain Stimulation as Add-on Treatment in Chronic Migraine With Medication Overuse

Identification of Predictors of Treatment Response and Innovative Therapeutic Strategies Based on Non-Invasive Brain Stimulation in Patients With Chronic Migraine and Medication Overuse

This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy of non-invasive brain stimulation as an add-on treatment to standard detoxification therapy in patients with chronic migraine and medication overuse. The study also seeks to identify sensory and biochemical biomarkers predictive of treatment response.

The main study is a randomized controlled trial enrolling patients with chronic migraine and medication overuse (MoH). Participants will undergo a standardized in-hospital detoxification protocol and will be randomly assigned to one of three parallel groups to receive either sham stimulation, active repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex face representation, or active rTMS applied over the motor cortex forearm representation. Stimulation will be delivered for five consecutive days.

Clinical, sensory (Quantitative Sensory Testing, QST), and biochemical measures (plasma glutamate, serotonin, and calcitonin gene-related peptide, CGRP) will be collected at baseline and during follow-up.

Inclusion Criteria:

• Diagnosis of chronic migraine and medication overuse according to ICHD-3 criteria
• Ability to provide written informed consent

Exclusion Criteria:

• Major psychiatric disorders (e.g., major depressive disorder)
• Changes in preventive migraine therapy within the last 3 months
• Ongoing treatment with monoclonal antibodies for migraine prevention
• Other significant neurological or systemic diseases
• Pregnancy
• Contraindications to transcranial magnetic stimulation (for main study participants)