BACKGROUND: Physical therapy is a non-pharmacological approach for migraine management. However, the effectiveness of a multimodal approach combining manual therapies. cervical exercises. and therapeutic education. compared to these interventions individually, remains unclear. OBJECTIVES: to investigate the effects of a multimodal approach versus manual therapies or pain neuroscience education alone in migraine patients. METHODS: A three-arm, parallel, single-blind. randomized clinical trial was conducted over 12 weeks, with assessments at baseline, 4, 8, and 12 weeks, and follow-up assessments at 1, 2, and 4 months. Seventy-five participants were randomly allocated to the Therapeutic Education Pain Neuroscience Group (TEG), Manual Therapies Group (MTG), or Multimodal Group (MUG). The primary outcome was the Headache Impact Test (HIT-6). Secondary outcomes included headache frequency, intensity, and duration; neck disability index (NDI); Allodynia Symptom Checklist (ASC-12); maladaptive beliefs; pain catastrophizing; quality of life; dizziness; and cervical assessments. Mixed models were analyzed in SPSS, considering group, time, and group-by-time interactions. RESULTS: All groups demonstrated significant HIT-6 improvement (p < 0.001). MTG showed greater improvement at week 4, while TEG surpassed MTG by week 12. At follow-up, MUG demonstrated superior reduction in headache impact. Significant group-by-time interactions favored multimodal treatment for headache frequency, intensity, neck pain, ASC-12, NDI, quality of life, and Flexion Rotation Test (p < 0.01). Also, MUG showed clinically relevant changes in NDI, Pain Catastrophizing Scale, quality of life, ASC-12, and Tampa Scale for Kinesiophobia. CONCLUSION: Although all treatments were effective, MUG was superior in sustaining reductions in headache impact at follow-up, and improving psychosocial, headache and neck-related outcomes.

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