Investigations on psychological variables and migraine have confirmed a strong association between migraine and depression or migraine and anxiety disorders. In particular patients suffering from chronic migraine with medication overuse have an elevated risk of mood and anxiety disorders, which may compromise treatment efforts. The aim of this study was to investigate a group of patients suffering from CM with medication overuse before and after inpatient withdrawal program after a long-term follow-up to examine clinical indexes and psychological variables changes in particular anxiety and depression by using Spielberger State-Trait Anxiety Inventory (STAI) 1, 2 and Zung Self-rating Depression Scale (Zung) tests, in order to verify if a specific psychological pattern in these patients is present, and if changes in psychological variables correspond with clinical improvement. The changes of clinical indexes and of psychological parameters are discussed and analyzed in order to address the most adequate therapeutic strategy for this kind of patients.