Behavioral Intervention in Medication Overuse Headache: A Double-Blind Randomized Clinical Trial

Background: Medication overuse headache (MOH) is a prevalent and highly disabling disorder, with a strong biobehavioral component. Hence, behavioral interventions might effectuate reduction of overused medication. We assessed in a double blind manner the efficacy of a behavioral intervention during medication withdrawal therapy.  Methods: In this concealed, double-blind, randomised controlled trial in MOH patients with underlying migraine we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy at the outpatient Headache Clinic of the Leiden University Medical Centre. Maximal intervention consisted of an intensive contact schedule, comprising of education, motivational interviewing and value-based activity planning during the 12 weeks of acute withdrawal. Minimal intervention consisted of one short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating the added value of botulinum toxin A to withdrawal therapy. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period.  Findings: From December 2012 to February 2016, we enrolled 179 patients (90 maximal intervention; 89 minimal intervention). At week 12, most patients achieved withdrawal in both groups (82/90 (93%) maximal intervention versus 75/89 (86%) minimal intervention, OR 2∙44 (95%CI 0∙83;7∙23), p=0∙107). At week 24, patients in the maximal intervention group had fewer acute medication days per month (mean difference -2∙23, 95%CI: -3∙76;-0∙70, p=0∙005).  This difference receded over time.  Interpretation: Intensive behavioral intervention by a headache nurse during withdrawal therapy for MOH patients is beneficial to reduce acute medication use during and shortly after the intervention, but extension of guidance seems warranted for a prolonged effect. The concealed study design may also be useful to investigate non-pharmacological therapies in other disorders.  Trial Registration: CHARM study; www.trialregister.nl, NTR3440. Funding Statement: Supported by grants from the Netherlands Organization for Scientific Research (Terwindt VIDI 917-11-31) and the Dutch Brain Foundation (2013(1)-247). Declaration of Interests: The authors report no relevant disclosures. Ethics Approval Statement: The study was performed in accordance with the declaration of Helsinki Ethical Principles and Good Clinical Practices and was approved by the local and national ethics committees.