Long term headache duration is a factor predicting nonresponse to detoxification and advice in medication overuse headache

Medication-overuse headache (MOH) is a secondary chronic headache having a relevant impact in clinical practice, with a prevalence of 1-2% in the general population [1‐3]. MOH is a very heterogeneous disorder for which a recommended treatment is not yet available. The management of MOH currently represents a difficult challenge for clinicians and headache experts [4]. A possible treatment choice is detoxification and the initiation of a prophylactic therapy [5, 6]. Nevertheless, the timing of this prophylactic treatment after detoxification remains one of the most debated aspects of MOH care [7] and a matter of concern among patients [8]. In a recent randomized open-label trial, a structured inpatient detoxification program, characterized by the immediate start of a preventive treatment, resulted more effective than advice alone or a structured outpatient program to achieve drug withdrawal [9]. Likewise, the Sodium vAlproate in the treatment of Medication Overuse HeadAche (SAMOHA) study recently showed the efficacy and safety of sodium valproate (VPA), compared to placebo, after detoxification in the short-term treatment of MOH patients with a history of migraine without aura [10]. In light of this, we analyzed data obtained from patients in both arms of the SAMOHA study, in search of demographic and clinical characteristics which could predict a response to detoxification and advice to withdraw from drug abuse.

For patients in the VPA arm, no differences between R and NR were observed fordemographic, clinical and headache characteristics (Table 1). Conversely, for patients in the placebo group, treated by detoxification and advice to withdraw from MOH, a significant difference between R and NR was found only for headache duration, while all the other variables were evenly distributed (Table 2). Specifically, in MOH patients with a history of migraine longer than 30 years, the probability of response to detoxification and advice to withdraw from drug abuse was irrelevant.

With reference to psychiatric comorbidity and personality traits, none of the assessed inventories differed between R and NR (data not shown).

To our knowledge, this is one of the few studies analyzing a possible correlation between demographic, clinical and headache characteristics of MOH patients and response to treatment. Our findings suggest that, in presence of a headache lasting more than 30 years, patients seem to have no benefit from detoxification and advice to withdraw from drug abuse, despite the possible placebo effect. Previously, in a cross-sectional epidemiological survey, the severity of dependence scale score could predict successful prognosis related to detoxification in MOH patients without other complicating secondary headaches [16].

The challenge of achieving a stable withdrawal from medication overuse is one of the most disputed aspects in the treatment of MOH. This lack of agreement is, for the most part, due to the heterogeneity of patients, overused medications, detoxification procedures and protocol designs [17].

Detoxification is often the first step in withdrawal from medication overuse. In this regard, some studies have suggested benefits from detoxification followed by advice for MOH [9]. Other studies have supported the efficacy of simple advice as a withdrawal strategy in MOH [18, 19]. However, in most of these studies there were no controls nor comparisons between responders and non-responders.

The results from our study suggest that in MOH patients with a history of headache longer than 30 years, even in the absence of relevant comorbidities, there is no benefit from detoxification and advice without preventive therapy. This lack of benefit could be due to the lingering central sensitization underlying the pathophysiology of MOH [17]. In these cases, we would suggest an immediate initiation of a prophylactic treatment, to avoid a relapse of drug abuse. This therapeutic approach could lead to a swifter clinical response, better quality of life and economic savings. It is also interesting that MOH duration did not differ in R and NR; this aspect should be further investigated, in order to hypothesize common or different pathophysiological mechanisms for migraine and MOH.

Our study has some limitations. First, the available sample size is incompatible with definitive results regarding the demographic and clinical characteristics we investigated. Given the small numbers, we could not perform a multivariate analysis of our data. So, headache duration may be masked by other confounding variables. Second, some of the patients in our study were included in the placebo arm of the SAMOHA study and, as such, they did not know if they were untreated. Even if a placebo effect cannot be ignored in MOH patients, the validity of our research hypothesis is weakened but not entirely excluded. Third, as our study analyzed the short-term efficacy of treatment, the long-term response to detoxification and advise is unknown.

In conclusion, in the case of headache of long duration our findings suggest that the benefit from detoxification and advice can be excluded in MOH patients. Therefore, a preventive treatment is suggested for these patients. Larger studies with longer follow-up are needed on this issue as their results could lead to a better management of MOH patients.