IMPORTANCE Medication overuse headache (MOH) is a disabling, globally prevalent disorder representing a well-known and debated clinical problem. Evidence for the most effective treatment strategy is needed.OBJECTIVE To compare 3 treatment strategies for MOH. DESIGN, SETTING, AND PARTICIPANTSThis open-label, randomized clinical trial with 6 months of follow-up was conducted in the tertiary sector at the Danish Headache Center, Glostrup, from October 25, 2016, to June 28, 2019. Of 483 patients with MOH referred during the inclusion period, 195 met the criteria consisting of migraine and/or tension-type headache, 18 years or older, eligibility for outpatient treatment, no severe physical or psychiatric disorder, no other addiction, and not pregnant or breastfeeding. Of these, 75 refused participation and 120 were included. Data were analyzed from July 3 to September 6, 2019.INTERVENTIONS Random assignment (1:1:1 allocation) to 1 of the 3 outpatient treatments consisting of (1) withdrawal plus preventive treatment, (2) preventive treatment without withdrawal, or (3) withdrawal with optional preventive treatment 2 months after withdrawal. MAIN OUTCOMES AND MEASURESThe primary outcome was change in headache days per month after 6 months. Predefined secondary outcomes were change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cured MOH. RESULTSOf 120 patients, 102 (mean [SD] age, 43.9 [11.8] years; 81 women [79.4%]) completed the 6-month follow-up. Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal plus preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20). No difference was found in reduction of migraine days per month, use of short-term medication, or headache intensity. In the withdrawal plus preventive group, 23 of 31 patients (74.2%) reverted to episodic headache, compared with 21 of 35 (60.0%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group (P = .03). Moreover, 30 of 31 patients (96.8%) in the withdrawal plus preventive group were cured of MOH, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). These findings corresponded to a 30% (relative risk, 1.3; 95% CI, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = .03).CONCLUSION AND RELEVANCE All 3 treatment strategies were effective, but based on these findings, withdrawal therapy combined with preventive medication from the start of withdrawal is recommended as treatment for MOH.

Background There is lack of evidence on how to detoxify medication-overuse headache. Aim To compare the effect of complete stop of acute medication with restricted intake. Methods Medication-overuse headache patients were included in a prospective, outpatient study and randomized to two months' detoxification with either a) no analgesics or acute migraine-medication (program A), or b) acute medication restricted to two days/week (program B). Detoxification was followed by preventives if indicated. Patients were followed up at 2, 6 and 12 months. Percentage reduction in headache days/month after 6 months was the primary outcome. Results We included 72 medication-overuse headache patients with a primary migraine and/or tension-type headache diagnosis. Fifty-nine completed detoxification, 58 (81%) were followed up at month 6 and 53 (74%) at month 12. At month 6, program A reduced headache days/month by 46% (95% CI 34-58) compared with 22% (95% CI 11-34) in program-B ( p = 0.005), and 70% in program A versus 42% in program B were reverted to episodic headache ( p = 0.04). Migraine-days/month were reduced by 7.2 in program A ( p < 0.001) and 3.6 in program B ( p = 0.002) after 6 months. Conclusion Both detoxification programs were very effective. Detoxification without analgesics or acute migraine-medication was the most effective program. Trial registration Clinicaltrials.gov (NCT02903329).

Background Medication-overuse headache is prevalent, but in principle preventable. Objective To describe the Danish national awareness campaign for medication-overuse headache. Methods The Danish Headache Center, the Association of Danish Pharmacies, and headache patient organizations implemented a four-month medication-overuse headache awareness campaign in 2016. Target groups were the general public, general practitioners, and pharmacists. Key messages were: Overuse of pain-medication can worsen headaches; pain-medication should be used rationally; and medication-overuse headache is treatable. A range of communication technologies was used. A survey on the public's awareness of medication-overuse headache was conducted. Results The Danish adult population is 4.2 million. Online videos were viewed 297,000 times in three weeks. All 400 pharmacies received campaign materials. Over 28,000 leaflets were distributed. Two radio interviews were conducted. A television broadcast about headache reached an audience of 520,000. Forty articles were published in print media. Information was accessible at 32 reputable websites and five online news agencies. Three scientific papers were published. Information was available at an annual conference of general practitioners, including a headache lecture. The survey showed an increase in percentage of the public who knew about medication-overuse headache (from 31% to 38%). Conclusion A concerted campaign to prevent medication-overuse headache can be implemented through involvement of key stakeholders.

Background Medication-overuse headache is a costly disease for individuals and society. Objective To estimate the impact of medication-overuse headache treatment on direct and indirect headache-related health care costs. Methods This prospective longitudinal study was part of the COMOESTAS project (COntinuous MOnitoring of Medication Overuse Headache in Europe and Latin America: development and STAndardization of an Alert and decision support System). Patients with medication-overuse headache were included from four European and two Latin American headache centers. Costs of acute medication, costs of health care services, and measurements of productivity were calculated at baseline and at 6-month follow-up Treatment consisted of overused drug withdrawal with optional preventive medication. Results A total of 475 patients (71%) completed treatment and were followed up for 6 months. Direct health care costs were on average reduced significantly by 52% ( p < 0.001) for the total study population. Significant reductions were seen in both number of consumed tablets (-71%, p < 0.001) and number of visits to physicians (-43%, p < 0.001). Fifty percent of patients reduced their number of consumed tablets ≥ 80%. Headache-related productivity loss, calculated either as absence from work or ≥ 50% reduction of productivity during the workday, were reduced by 21% and 34%, respectively ( p < 0.001). Conclusion Standardized treatment of medication-overuse headache in six countries significantly reduced direct health care costs and increased productivity. This emphasizes the importance of increasing awareness of the value of treating medication-overuse headache. Trial registration The trial was registered at ClinicalTrials.gov (no. NCT02435056).

Background Complete stop of acute medication and/or migraine medication for treatment of medication‐overuse headache (MOH) has previously been reported more effective in reducing headache days and migraine days per month compared with restricted intake of acute medication. However, it is unknown whether complete stop or restricted intake is the most feasible treatment for patients. Objectives To investigate whether feasibility of withdrawal in MOH is different between complete stop of acute medication and restricted intake, and whether reductions in headache‐related medication dependence, anxiety and depression differ between the treatments. Methods Medication‐overuse headache patients were included in a prospective, open‐label, outpatient study and randomized to two months of withdrawal with either no analgesics or acute migraine medication (programme A) or acute medication restricted to 2 days/week (programme B). After 6 and 12 months, patients graded feasibility of withdrawal. Dependence was measured by Severity of Dependence Scale (SDS), while anxiety and depression were measured by Hospital Anxiety and Depression Scale (HADS). Results We included 72 MOH patients with primary migraine and/or tension‐type headache. Forty‐nine completed withdrawal and the SDS questionnaire at 12‐month follow‐up, and the feasibility of withdrawal was significantly higher in programme A compared to programme B (p < 0.001). At 12 months, the dependence was reduced by 44% in programme A compared to 26% in programme B (p = 0.053), while the anxiety score was reduced by 32% and 11%, respectively (p = 0.048). Conclusions Withdrawal with complete stop of acute medication was more feasible and most effective in reducing headache‐related anxiety compared with restricted intake. Significance A complete stop of all analgesics is the most effective treatment for MOH regarding reduction in headache days but has often been regarded as too challenging for patients. However, in this study, complete stop appears to be more feasible compared with restricted intake of analgesics seen from the patients’ perspective.

Background Medication-overuse headache leads to high disability and decreased quality of life, and the best approach for withdrawal has been debated. Aim To compare change in disability and quality of life between two withdrawal programs. Methods We randomized medication-overuse headache patients to program A (two months without acute analgesics or migraine medications) or program B (two months with acute medications restricted to two days/week) in a prospective, outpatient study. At 6 and 12 months, we measured disability and headache burden by the Headache Under-Response to Treatment index (HURT). We estimated quality of life by EUROHIS-QOL 8-item at 2-, 6-, and 12-month follow-up. Primary endpoint was disability change at 12 months. Results We included 72 medication-overuse headache patients with primary migraine and/or tension-type headache. Fifty nine completed withdrawal and 54 completed 12-month follow-up. At 12-month follow-up, 41 patients completed HURT and 38 completed EUROHIS-QOL 8-item. Disability reduction was 25% in program-A and 7% in program-B ( p = 0.027). Headache-burden reduction was 33% in program-A and 3% in program-B ( p = 0.005). Quality of life was increased by 8% in both programs without significant difference between the programs ( p = 0.30). At 2-month follow-up, quality of life increased significantly more in program-A than program-B ( p = 0.006). Conclusion Both withdrawal programs reduced disability and increased quality of life. Withdrawal without acute medication was the most effective in reducing disability in medication-overuse headache patients. Trial registration Clinicaltrials.gov (NCT02903329).

Headache and facial pain are among the most common, disabling and costly diseases in Europe, which demands for high quality health care on all levels within the health system. The role of the Danish Headache Society is to educate and advocate for the needs of patients with headache and facial pain. Therefore, the Danish Headache Society has launched a third version of the guideline for the diagnosis, organization and treatment of the most common types of headaches and facial pain in Denmark. The second edition was published in Danish in 2010 and has been a great success, but as new knowledge and treatments have emerged it was timely to revise the guideline. The recommendations for the primary headaches and facial pain are largely in accordance with the European guidelines produced by the European Academy of Neurology. The guideline should be used a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organized in Denmark. This description is followed by sections on the characteristics, diagnosis and treatment of each of the most common primary and secondary headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular challenges regarding migraine and female hormones as well as headache in children are addressed.

Background Dependence‐like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence‐like behaviour is unknown. Objectives To compare patient‐reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to 6 months. Methods Patients with MOH were randomized to (1) withdrawal combined with preventive medication from start (W+P), (2) preventive medication without withdrawal (P), or (3) withdrawal with optional preventive medication 2 months after withdrawal (W). At baseline, 2, and 6 months, patients filled out SDS (used for measurements of dependence‐like behaviour and treatment feasibility), Headache Under‐Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires. Results Out of 120 patients with MOH, 100 completed the 6‐month follow‐up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After 6 months, the SDS score was reduced by 3.69 (95% CI 3.23–4.49) in the W+P arm, by 3.19 (95% CI 2.43–3.96) in the W arm, and by 1.65 (95% CI 0.96–2.33) in the P arm (p = 0.04). At baseline and after 2 months, the P arm was considered the most feasible treatment, but at 6‐month follow‐up, there was no difference in feasibility score, change in HURT score, or quality of life. Conclusions Dependence‐like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH. Significance Withdrawal combined with preventive medication from start is the treatment strategy that reduces dependence‐like behaviour the most in MOH patients. Patients initially considered preventive treatment without withdrawal as the most feasible treatment. However, no difference in feasibility between the three arms was found at 6‐month follow‐up. Withdrawal combined with preventive medication is recommended for treatment of MOH.