• bipolar spectrum disorders
• chronic migraine
• cyclothymia
• emotional dysregulation
• medication overuse headache
• psychiatric comorbidity

Background: Migraine is a disabling neurological disorder characterized by episodic attacks of moderate or severe headache along with reversible neurological and systemic symptoms, such as photophobia, phonophobia, and gastrointestinal symptoms. Especially in patients suffering from chronic migraine (CM), the disorder is associated with a wide range of psychiatric diseases. Overuse of acute migraine medications is one of the most important factors involved in the conversion from episodic migraine (EM) to CM along with obesity, smoking, high caffeine intake, low socioeconomic status, cutaneous allodynia, chronic pain conditions, sleep disorders, respiratory conditions, selected psychiatric disorders and stressful life events. Medication overuse headache (MOH) is defined as a headache occurring on 15 or more days/month in subjects suffering from a pre-existing primary headache and developing as a consequence of a frequent or excessive use of symptomatic medications for more than 3 months. Several studies reported an increased prevalence of psychiatric disorders in patients with MOH suggesting that the presence of psychopathological alterations may predict chronic course and inadequate response to pharmacological treatment.
Purpose: The aim of this study was to explore psychiatric comorbidity in a sample of adult chronic migraineurs comparing clinical characteristics between patients with and without MOH.
Methods: Seventy-five patients with CM were recruited from the Headache center at Neurology Unit of Santa Chiara Hospital in Pisa. All patients were assessed using the brief version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego self-questionnaire (brief TEMPS-M), the Reactivity Intensity Polarity Stability Questionnaire (RIPoSt-40), the Adult Self-Report Scale (ASRS-v 1.1), the Morningness-Eveningness Questionnaire Self-Administered (MEQ-SA), the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRADDS), the Clinical Global Impression (CGI), the Global Assessment of Functioning Scale (GAF), the Headache Impact Test (HIT-6), the Allodynia Symptom Checklist (ASC-12), and the Fatigue Assessment Scale (FAS). We divided the sample in two groups on the basis of the comorbidity with MOH, evaluating the clinical differences and exploring the possible link between psychiatric comorbidity and MOH.
Results: MOH (n=41) and N-MOH (n=34) patients differed significatively from each other for age at onset of migraine (15 years vs 23 years; p=0.002), for the comorbidity with mood disorders (75.6% vs 52.9%; p=0.040), especially bipolar spectrum disorders (70.7% vs 47.1%; p=0.037) mostly represented by cyclothymia (63.4% vs 35.3%; p=0.015). As regard to somatic comorbidities, MOH subjects presented with fewer neurological abnormalities compared to N-MOH patients (9.8% vs 38.2%; p=0.003). In addition, there was a statistical significant difference between the two groups regarding symptomatic medications (100% vs 88.2%; p=0.024) and anti-CGRP monoclonal antibodies treatment (19.5% vs 0%; p=0.006). Furthermore, as assessed by psychometric scales, significant discrepancies were detected in the brief-TEMPS-M subscales of cyclothymic temperament (p=0.049), in the RIPoSt subscale of affective instability (p=0.0043) and in the WRADDS emotional dysregulation (ED) related subscales (p=0.044). Moreover, MOH patients showed an early chronotype less frequently than N-MOH subjects (41.5% vs 67.6%; p=0.024), as assessed by the MEQ-SA. Regarding the severity of psychiatric illness, CGI scores were found higher in MOH patients compared to N-MOH subjects (p=0.019).
Conclusions: In our sample patients with MOH reported higher rates of comorbid mood disorders, in particular bipolar spectrum disorders and cyclothymia, as well as higher levels of affective instability and emotional dysregulation and lower response to first-line oral preventive strategies. Our results seems to suggest that a systematic assessment of psychiatric comorbidity in MOH patients may lead to a more appropriate management of these complex subset of patients. Further longitudinal studies are needed to assess the exact role of psychiatric comorbidity in the development of chronic migraine and MOH.