The psychopathological profile of patients with medication overuse headache appears to be particularly complex. To better define it, we evaluated their performance on a targeted psychological profile assessment. We designed a case-control study comparing MOH patients and matched healthy controls. Headache frequency, drug consumption, HIT-6, and MIDAS scores were recorded. All participants filled in the following questionnaires: Beck Depression Inventory-II Edition, trait subtest of State-Trait Anxiety Inventory, Difficulties in Emotion Regulation Scale, Barratt Impulsiveness Scale, Toronto Alexithymia Scale. The primary endpoint (...) was to establish if MOH patients have an altered psychopathological profile. The secondary endpoint was to establish whether the worst profile correlates with the worsening of headache and disability measures. We enrolled 48 consecutive MOH patients and 48 HC. MOH patients showed greater difficulty in recognition/regulation of emotions, depression, anxiety, and impulsiveness. We found a positive correlation among DERS, BDI-2, STAI-Y, and BIS scores and MIDAS and HIT-6 scores and among DERS and headache frequency and drug consumption. MOH patients showed a high rate of emotion regulation difficulties, depression, and anxiety, which may negatively affect their headaches. The ability to regulate/recognize emotions may play a central role in sustaining medication overuse. (shrink)