Comparison of Two Detoxification Protocols for Treatment of Medication-overuse Headache

Study Overview
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Brief Summary
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Medication-overuse headache (MOH) is a common, costly and disabling disorder affecting approximately 63 million people worldwide. MOH is a potentially treatable condition, and there are different opinions among headache specialists concerning the correct treatment strategy. The study is a prospective longitudinal open-label randomized controlled study comparing two detoxification programs conducted in a tertiary headache care center. Patients with MOH are either randomized to treatment in program A or program B. In program A, patients undergo detoxification without any acute medication during a two months period (complete stop of acute medication intake). In program B, patients was allowed to take up to 2 days a week with analgesics or migraine medication during the two months detoxification period (restricted acute medication intake). Both A and B are out-patient programs, and patients in both groups receive patient education, consisting of six lessons, managed by specialized headache nurses in collaboration with specialized psychologists and physiotherapists (Figure 1). All patients are also offered rescue medication (levomepromazine or promethazine) and antiemetics, if necessary. The need for prophylactic treatment is evaluated individually after 2-month detoxification. Patients are followed-up at 2, 6 and 12 months after detoxification. All patients are asked to continuously register headache calendar and to fulfill questionnaires at all the follow-up visits. In addition they are asked to fill out questionnaires (Headache Under-Response to Treatment (HURT), Hospital Anxiety and Depression Score (HADS), Severity of Dependence Score (SDS), World Health Organization Quality of Life Score(WHO QoL) and Dolo-score) at baseline, 2, 6 and 12 months

Detailed Description
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Patients with contact to Danish headache center are recruited consecutively. The MOH-diagnosis is based on least 3 months previous detailed history and at least 1 month fulfilled headache diary or headache calendar prior to the visit. Patients were allocated to either program A or B by a concealed randomization process. The patients were randomized in blocks of 10 by use of opaque, sealed envelopes. Statistics Statistical Package for Social Sciences (SPSS) version 22 is used for statistical calculations. Continuous variables are presented as mean (SD) and median (25-75 percentiles). For normal distributed continuous variables the investigators use paired and unpaired student's T-test, while for skewed distribution the investigators used Mann-Whitney test. Categorical variables is presented as percentage (N), and analyzed by chi-square test. All results are shown as intention-to-treat (ITT). The p-value is two-sided and p ≤ 0.05 is considered as significant. The primary outcome is reduction in headache days per month. Clinical relevant difference is estimated to 20% between the two groups. The standard deviation based on previous published literature was estimated to 35%. Accepting an alfa-error on 5% and 80% power, 80 patients are needed. Based on previous studies, it is assumed that the drop-out rate will be approximately 15-20%. Therefore the investigators aim to include 100 patients corresponding to 50 in each group.

Official Title
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Efficacy of Restricted Acute Medication Intake Compared to no Acute Medication Intake During a Two Months Detoxification Period in Medication-overuse Headache

Conditions
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Medication-overuse Headache

Intervention / Treatment
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* Other: Detoxification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MOH-diagnosis according to ICHD-3beta Eligible for out-patient care Previously diagnosed with primary headache forms. Exclusion Criteria: Previously diagnosed with secondary headache forms Significant physical or psychiatric illness Pregnancy or breastfeeding Inadequate language skills to follow the patient education and filling out questionnaires.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protocol A<br>In program A, patients underwent detoxification without any acute medication during a two months period (complete stop of acute medication intake). | Other: Detoxification<br>* Two ways of composing the detoxification protocol<br>* Other names: Treatment for MOH;|
| Active Comparator: Protocol B<br>In program B, patients were allowed to take up to 2 days a week with analgesics or migraine medication during the two months detoxification period (restricted acute medication intake). | Other: Detoxification<br>* Two ways of composing the detoxification protocol<br>* Other names: Treatment for MOH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache frequency |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days with acute medication/ month |  | 6 and 12 month | 
| Headache frequency |  | 12 months | 
| Headache intensity (Total intensity per month meassured by headache calendars). | Patients daily register headache intensity by 0,1, 2 or 3 corresponding to the intensity. The headache intensity is summed up for 30 days. | 6 and 12 months | 
| Scores from questionnaires Headache Under-Response to Treatment (HURT) |  | 6 and 12 months | 
| Scores from questionnaires Hospital Anxiety and Depression Score (HADS) |  | 6 and 12 months | 
| Scores from questionnaires World Health Organization Quality of Life score |  | 6 and 12 months | 
| Scores from questionnaires Severity of Dependence Score (SDS) |  | 6 and 12 months | 
| Scores from questionnaires Dolo-score |  | 6 and 12 months |