Treatment of medication overuse headache: Effect and predictors after 1 year-A randomized controlled trial.

BACKGROUND: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking. OBJECTIVE: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year. METHODS: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year. RESULTS: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported. CONCLUSIONS: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.

Reference programme: diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 3rd edition, 2020.

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.

Dependence-like behaviour in patients treated for medication overuse headache: A prospective open-label randomized controlled trial.

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.

Treatment of medication overuse headache-A review.

Medication overuse headache (MOH) is the most prevalent chronic headache disorder with a prevalence between 1% and 2% worldwide. The disease has been acknowledged for almost 30 years, yet experts still disagree on how best to treat MOH. By performing a search in PubMed on the terms "medication overuse headache," "analgesics abuse headache," "rebound headache," "drug induced headache," and "headache AND drug misuse" limited to human studies published in English between January 1, 2004, and November 1, 2017, we aimed to evaluate current literature concerning predictors of treatment outcome, inpatient and outpatient treatment programs, initial versus latent administration of prophylactic medications, and to review the effect of prophylactic medications. Selection criteria were prospective, comparative, or controlled trials on treatment of MOH in persons of at least 18 years of age. Several studies evaluated risk factors to predict the outcome of MOH treatment, but many studies were underpowered. Psychiatric comorbidity, high dependence score, and overuse of barbiturates, benzodiazepines, and opioids predicted a poorer outcome of withdrawal therapy. Patients with these risk factors benefit from inpatient treatment, whereas patients without risk factors benefit equally from inpatient and outpatient treatment. Some medications for migraine prophylactics have shown better effect on MOH compared with placebo, but not when combined with withdrawal. We conclude that detoxification programs are of great importance in MOH treatment. Latent administration of prophylactic medications reduces the number of patients needing prophylactic medication. Individualizing treatment according to the predictors of outcome may improve treatment outcome and thus reduce work-related and treatment-related costs.

Circulating nociceptin and CGRP in medication-overuse headache.

BACKGROUND: Previous studies found low serum levels of nociceptin in migraine patients but high serum levels of calcitonin gene-related peptide (CGRP). CGRP can elicit migraine-like headache. Medication-Overuse Headache (MOH) often has migraine features and can mimic chronic migraine. We therefore hypothesized that as in migraine, serum levels of nociceptin would be lower and CGRP serum levels higher in MOH patients compared with those in healthy volunteers. We hypothesized that the serum levels would normalize after detoxification. METHODS: Seventeen MOH patients, hereof 70.6% with chronic migraine and MOH, and 30 sex and age matched headache-free controls were included. MOH patients underwent a 2-month outpatient detoxification program and after 6 months, 10 patients and 19 controls were retested. Blood samples were analyzed blinded. RESULTS: We found no differences in the levels of nociceptin and CGRP between MOH patients and controls (P = 0.65 and P = 0.59). The mean headache frequency reduction was 43% and 70% of patients reverted to episodic headache after 6 months, but the levels of nociceptin and CGRP were unchanged (P = 0.71 and P = 0.82). CONCLUSION: In contrast to previous findings in migraine patients, we found normal serum levels of nociceptin and CGRP in MOH patients. Thus, we find no evidence that the increased headache frequency of MOH patients could be caused by altered nociceptin and CGRP levels. This underlines the importance of identifying medication overuse in chronic headache and treating the MOH.

Medication overuse headache.

BACKGROUND: Medication overuse headache (MOH) affects between 1% and 2% of the general population but is present in up to 50% of patients seen in headache centers. There are currently no internationally accepted guidelines for treatment of MOH. METHODS: A review of the current literature on MOH treatment and pathophysiology. RESULTS: We conclude that headache frequency can be reduced to episodic headache in more than 50% of the patients by simple detoxification and information. Approximately half the patients will not have need for prophylactic medication after withdrawal. Pain perception is altered in patients with MOH but can be restored to a baseline pattern, indicating a reversible mechanism in the central sensitization leading to chronic pain. The great comorbidity with depression and anxiety could be a consequence of the altered serotonin metabolism indicating a reversible and potentially treatable condition. CONCLUSION: Increased focus on MOH is extremely important, as MOH both can and should be treated and prevented. MOH is thus a diagnosis that should be considered in all chronic headache patients as the very first step in their management strategy. In the general population, prevention campaigns against MOH are essential to minimize chronic pain disability.

Modulation of central sensitisation by detoxification in MOH: results of a 12-month detoxification study.

BACKGROUND: Human and animal models suggest that central sensitisation plays a role in medication-overuse headache (MOH). We aimed to study pain perception in MOH patients before and a year after withdrawal. METHODS: We examined pain perception in 35 MOH patients before and two, six and 12 months after detoxification. For baseline comparison, we tested 40 healthy controls. We measured cephalic and extra-cephalic pressure-pain thresholds and supra-threshold pressure-pain scores and extra-cephalic pain thresholds, supra-threshold pain scores and temporal summation for electrical stimulation. RESULTS: Of the 35 patients, 21 patients completed the entire study and remained cured of MOH. Statistically significant differences between patients and healthy controls were found in cephalic pressure-pain thresholds (137.3 kPa vs. 170 kPa, P < 0.05), extra-cephalic pressure pain thresholds (213.3 vs. 274.3 kPa, P < 0.05), in cephalic supra-threshold pressure-pain scores measured on a 100 mm visual analogue scale (61 vs. 27 mm, P < 0.05) and extra-cephalic supra-threshold pain scores for electrical stimulation (19.0 vs. 10.0 mm, P < 0.05). Cephalic supra-threshold pain scores decreased statistically significantly from 50.3 mm at baseline to 28.0 mm at the 12-month follow-up. In contrast to controls, temporal summation was not found in MOH patients before withdrawal, but after detoxification temporal summation normalised. CONCLUSION: The central nervous system is sensitised in patients with MOH. For the first time we demonstrate that the pain perception continues to normalise up to a year after detoxification. This emphasises the importance of detoxification and follow-up to prevent relapse.

Detoxification of medication-overuse headache by a multidisciplinary treatment programme is highly effective: a comparison of two consecutive treatment methods in an open-label design.

BACKGROUND: Evidence for optimal medication-overuse headache treatment is lacking. Some experts suggest reduced symptomatic medication with prophylactics from the start of withdrawal, while others suggest a two-month drug-free period with multidisciplinary education. AIM: To examine the acceptability, feasibility and outcome of these two regimes in a non-randomised open-label study. METHODS: Patients able to undergo outpatient detoxification, with medication-overuse headache that had previously been unsuccessfully treated by specialists and without significant co-morbidities were treated with (A) individual withdrawal with restricted symptomatic medication and prophylactics from Day 1 or (B) a two-month drug-free period and multidisciplinary education in groups. All patients received close one-year follow-up. RESULTS: Eighty-six of 98 patients completed follow-up. Both treatments proved highly effective-80.0% of Group A and 85.4% of Group B were cured of medication-overuse headache. Headache-frequency reduction was 40.2% in Group A and 38.4% in group B. In 48.9% of group A and 48.8% of group B, headache-frequency reduction was >50%. Programme B required fewer resources from the staff and only 61.9% of these patients needed prophylactics after two months compared with 84.8% in programme A. CONCLUSIONS: Both structured detoxification programmes proved highly effective with one-year close follow-up in previously treatment-resistant patients with medication-overuse headache. We suggest multidisciplinary education for patients in groups and delaying initiation of prophylactics until after the detoxification.

Treatment-resistant medication overuse headache can be cured.

OBJECTIVE: To evaluate the long-term efficacy of a structured, multidisciplinary treatment program in patients who had been treated unsuccessfully for medication overuse headache by specialists in an open-label design. BACKGROUND: Medication overuse headache is a common and disabling disease. Management is complicated by substantial treatment failure and relapse, and those who relapse and nonresponders to treatment are often excluded from studies on medication overuse headache. METHODS: Patients with medication overuse headache who had previously been unsuccessfully treated by specialists and referred to a specialized, tertiary headache centre were recruited. They underwent a structured 2-month detoxification program and were subsequently closely followed up for 10 months by a multidisciplinary team of physicians, nurses, physiotherapists, and psychologists. RESULTS: Eighty-six of 98 patients completed the study. PRIMARY OUTCOME: At 12-month follow-up, headache frequency was reduced by 39.3% (P < .001), 71 patients (82.6%) remained cured of medication overuse, reduction in headache frequency of more than 50% occurred in 42 patients (48.8%), and 52 (60.5%) reverted to episodic headache. Both of these figures had increased significantly from month 2 to month 12 (P < .001). Medication use was reduced by 62.8% (P < .001). CONCLUSION: Patients with medication overuse headache previously regarded treatment-resistant benefit considerably from multidisciplinary treatment in a structured detoxification program with close follow-up.

Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine.

Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer-testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according to the National Cancer Institute's common Toxicity Criteria. Four patients were graded with stable disease. Two remained stable throughout the entire study period. Analysis of changes in the patients' quality of life revealed stability in the subgroups: 'physical function' (p=0.872), 'physical role limitation' (p=0.965), 'bodily pain' (p=0.079), 'social function' (p=0.649), 'emotional role limitation' (p=0.252) and 'mental health' (p=0.626). The median survival from inclusion was 5.3 months (range 0.2-29.2 months) with one patient still being alive almost 30 months after inclusion in the trial. Treatment with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.