Despite advancements in migraine therapies, patients with comorbid conditions like fibromyalgia or subclinical hypothyroidism often experience suboptimal outcomes. Emerging treatments, such as CGRP monoclonal antibodies, are showing promise in these complex cases. Simultaneously, machine learning models are being developed to enhance risk stratification, potentially leading to more personalized and effective treatment plans.
Migraine management frequently stalls when standard protocols meet the layered pathology of fibromyalgia or thyroid dysfunction, leaving clinicians to navigate attacks that resist both preventative and abortive measures. Recognizing these diagnostic and therapeutic blind spots, headache specialists must now consider strategies that address not only neuronal pathways but also systemic contributors to pain.
Recent real‐world evidence points to targeted biologics that surpass traditional approaches. A retrospective monocentric observational study on the effectiveness of CGRP-targeting monoclonal antibodies demonstrated significant reductions in migraine frequency and severity in patients with fibromyalgia, alongside improvements in fibromyalgia-related disability and somatic pain. Updated data also reveal that both eptinezumab and erenumab can manage complex cases by reducing headache frequency and improving compliance among chronic migraine patients prone to medication‐overuse headaches.
Beyond pharmacotherapy, precision medicine is gaining traction through data-driven analytics. Machine learning models can analyze metabolic profiles, lifestyle factors and behavioral traits to predict and stratify the risk of migraines, transforming migraine risk stratification from a static assessment into an adaptive decision-support tool that guides personalized interventions.
Endocrine influences once relegated to secondary consideration are now integral to the therapeutic algorithm. A systematic review and meta-analysis have suggested that low-dose thyroxine therapy may reduce migraine frequency and severity in patients with subclinical hypothyroidism, reinforcing the necessity of routine thyroid function screening in refractory cases.
Integration of targeted anti-CGRP therapy, machine learning–derived risk models and proactive management of comorbid endocrine dysfunction offers a multipronged framework for clinicians aiming to improve outcomes in complex migraine presentations. As these innovative therapies and analytical tools become more accessible, practice patterns should evolve to include early biologic referral, collaborative risk assessment and interdisciplinary care pathways.