Of the subjects with headaches referred to tertiary care clinics, as many as 15-30% are affected with chronic migraine with symptomatic medication overuse (CMwMO) [
1]. Coping with the pain and disability associated with chronic migraine (CM) is likely to be a potential cause for increased medication intake [
2],[
3]. However, some subjects with CM lose control over the use of symptomatic medications and develop counterproductive behaviors, including decision making deficits that compromise social functioning and negatively impact the quality of life [
4]-[
6]. The underlying pathophysiology of CMwMO is poorly understood. Evidence from recent studies suggests that neurobiological factors yet to be identified, including aberrant resting state functional connectivity within the default-mode network and reduced gray matter volumes of frontal regions, precuneus and hippocampus, could predispose certain subjects with CM to fall and recurrently relapse into CMwMO [
7],[
8]. Currently, the initial line of treatment for CMwMO is detoxification from the offending drug [
9]. Nonetheless, studies conducted in tertiary care clinics with patient populations and detoxification protocols similar to ours indicated that 20-40% of those subjects who discontinue medication overuse after a successful detoxification relapse into it within a period of months or years [
10]. Longitudinal studies investigating variables associated with relapse following a successful detoxification have produced inconclusive result. Although the characteristics of CMwMO are considered to be outcome predictors associated with relapse [
11],[
12], longitudinal studies showed that neither the frequency nor the intensity of migraines is significantly associated with relapse rates [
10], instead suggesting that psychological and affective characteristics could play a key role. Mood disorders including depression have been considered relapse-predicting factors [
13]: a 4-year follow-up study conducted by Hagen et al. found that lower scores for depressive symptoms at baseline were the only factor associated with functional improvement [
14]. Furthemore, dysfunctional personality traits have been related to worsened long-term prognosis in subjects with CM
, and might facilitate the perpetuation of medication consumption [
15],[
16]. Third, the severity of dependency-like behaviors could dampen the benefits of detoxification and increase risk to fall into CMwMO [
17]. Finally, differences in attributing control over pain to particular influence the effectiveness of therapeutic interventions [
18]. Thus, subjects with CMwMO who tend to attribute control over pain to internal sources are more likely to rationalize painful perceptions as less-frequent, less-intense, and less-distressing. Subjects who attribute pain control to external domains, such as fate, luck, or medical treatment, are conversely more likely to show maladaptive coping strategies leading to greater functional impairment [
19],[
20]. We previously conducted an observational single-arm study on subjects with CMwMO referred to our headache center for a detoxification program. When looking at migraine characteristics and related disability prior-to, and then 1-year-after detoxification, we found that detoxification was associated with significant improvements in the group taken as a whole [
21]. In this retrospective analysis, we decided to study comparatively those who did not fall into medication overuse throughout the 12 months following the detoxification and those who relapsed into CMwMO. In addition, we aimed to characterize personality traits, dependency-like behaviors and pain coping styles in the two subgroups and to determine whether these factors could be possible predictors of relapse into CMwMO.