Is Detoxification Needed in Medication-overuse Headache?

Study Overview
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Brief Summary
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Medication-overuse headache (MOH) is a disabling condition, yet treatable. According to European guidelines and based on evidence, multidisciplinary detoxification is the first choice of treatment for MOH. However, consensus about the details in such detoxification programs is lacking. Contrary, other headache specialists believe more in treating chronic headache with medication overuse with single-therapy of prophylaxis and no withdrawal of acute medication, based on randomized controlled double-blinded placebo trial with prophylaxes. Only a single RCT has compared single-therapy with prophylaxis to detoxification. However there was no significant difference. AIM: To compare three different treatment protocols in order to improve the therapy of MOH. To test several baseline variables for being potential predictors for good treatment outcome. To examine the role of epigenetics in MOH.

Official Title
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Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies

Conditions
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Medication Overuse Headache

Intervention / Treatment
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* Other: Different well-known treatments


Participation Criteria
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Eligibility Criteria
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Patients with medication-overuse headache: Inclusion Criteria: Confirmed MOH diagnosis according to the ICHD-III beta (1). Eligible for outpatient treatment based on type of medication overuse (without massive pure opioids and barbiturates overuse), and personal resources and motivation. Capable of completing headache diary/calendar. Age ≥ 18 years old and capable of providing informed consent. Medication-overuse headache based on initial tension-type headache (TTH) or migraine. Signed informed consent. Exclusion Criteria: Severe physical illness or psychiatric disorders. Addiction to alcohol or other drugs. Current treatment with headache prophylaxis. Patients can be included minimum 5 weeks after stop of prophylaxis. Pregnancy, breastfeeding or planned pregnancy within the next 12 months. Inability to provide reliable information about medical history. Criteria for Control group 1 - Episodic migraineurs: Episodic migraine, with/without concomitant tension-type headache, according to the ICHD-III beta. Headache days / month ≤ 6 at time of inclusion. Days with analgesics / month ≤ 6 at time of inclusion. Prophylactics are allowed. Age ≥ 18 years old. Ability to fill out headache calendar. No previous medication overuse. No significant co-morbid pain, physical or psychiatric disorders. No addiction to alcohol or drug-abuse. No pregnancy, breastfeeding or planned pregnancy within the next 12 months. Criteria for Control group 2 - Healthy volunteers: •≥ 2 days with headache in the past month at time of inclusion. Days with analgesics / month ≤ 6 at time of inclusion. Age ≥ 18 years old. No significant co-morbid pain, physical or psychiatric disorders. No addiction to alcohol or drug-abuse. No pregnancy, breastfeeding or planned pregnancy within the next 12 months.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Detoxification and pharmacological prophylactic treatment<br>Group A: Two months detoxification program combined with pharmacological prophylactic treatment from start. | Other: Different well-known treatments<br> <br> |
| Active Comparator: Pharmacological prophylactic treatment<br>Pharmacological prophylactic treatment from start without detoxification. | Other: Different well-known treatments<br> <br> |
| Active Comparator: Detoxification<br>Two months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification. | Other: Different well-known treatments<br> <br> |
| No Intervention: Control group 1: Episodic migraine<br> | |
| No Intervention: Control group 2: Healthy volunteers<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in headache days per month in group A and C compared to group B. |  | Six months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in headache days per month | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two and 12 months follow-up and 4 years | 
| Reduction in days/month with use of analgesics and/or migraine medication. | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two, 6 and 12 months follow-up and 4 years | 
| Responders based on reduction in headache days / month (percentage with more than 30%, 50% and 75%). | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two, 6 and 12 months follow-up and 4 years | 
| Reduction in headache intensity. | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). This outcome will be presented as 1) Total headache intensity per month, and as 2) Visual Analogue Scale (VAS). | Two, 6 and 12 months follow-up and 4 years | 
| Descriptive report of self-reported adverse effects of treatments. | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two, 6 and 12 months follow-up | 
| Changes in Headache Under-Response to Treatment (HURT)-score. | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two, 6 and 12 months follow-up | 
| Drop-out rate. |  | One, 2, 4, 6, 9 and 12 months follow-up and 4 years | 
| Changes in Hospital Anxiety and Depression Scale (HADS). | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Six and 12 months follow-up | 
| Changes in Quality of Life (QoL) score. | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Six and 12 months follow-up | 
| Changes in Severity of Dependence Score (SDS). | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Six and 12 months follow-up | 
| Changes in Perceived Stress Score (PSS). | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Twelve months follow-up. | 
| Patient's satisfaction questionnaire | Group A and C versus group B. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis). Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis). | Two, 6 and 12 months follow-up |