Clinical and Therapeutic Approach to Primary Headaches: Differential Diagnosis and Evidence-Based Management

A Narrative Review with a Focus on Contemporary Clinical Implications

Abstract

Primary headaches constitute a highly prevalent and disabling group of neurological disorders, notably migraine, tension-type headache, and cluster headache, all of which exert substantial functional and socioeconomic impact. Despite advances in scientific knowledge, these conditions remain frequently underdiagnosed and inadequately managed. Recent studies have expanded the understanding of their pathophysiology, highlighting the involvement of the trigeminovascular system, neuroinflammatory mechanisms, the release of neuropeptides such as calcitonin gene-related peptide (CGRP), and central alterations demonstrated by neuroimaging techniques. The present study aims to review the clinical and therapeutic approach to primary headaches, with emphasis on differential diagnosis among their main subtypes and evidence-based management strategies. This narrative literature review was conducted through the analysis of scientific articles published in high-impact indexed journals, including systematic reviews, narrative reviews, and relevant studies addressing pathophysiology, diagnostic criteria, and therapeutic options. The findings indicate that accurate diagnosis relies on detailed clinical history and rigorous application of established diagnostic criteria, allowing appropriate exclusion of secondary headaches. Evidence-based management, encompassing conventional pharmacological therapies, targeted treatments such as anti-CGRP monoclonal antibodies, neuromodulation strategies, and non-pharmacological interventions, has demonstrated effectiveness in reducing attack frequency and severity. It is concluded that integration of pathophysiological knowledge with clinical practice is essential to optimize differential diagnosis and individualized treatment of primary headaches, thereby contributing to improved patient quality of life.