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1.  Feasibility of a brief intervention for medication-overuse headache in primary care – a pilot study 
BMC Research Notes  2014;7:165.
Background
Medication-overuse headache (MOH) is a common problem in primary care. Brief intervention (BI) has successfully been used for detoxification from overuse of alcohol and drugs. The aim of this pilot study was to develop and test methodology, acceptability and logistics for a BI for MOH in primary care.
Findings
Observational feasibility study of an intervention in a Norwegian general practice population.
Six general practitioners (GPs) were recruited. A screening questionnaire for MOH was sent to all 18–50 year old patients on these GPs` list. GPs were taught BI, which was applied to MOH patients as follows: Severity of dependence scale (SDS) scores were collected and individual feedback was given of the relationship between the SDS, medication overuse and headache. Finally, advice to reduce medication was given. Patients were invited to a headache interview three months after the BI. Main outcomes were feedback from GPs/patients about the feasibility and logistics of the study design, screening/recruitment process, BI and headache interviews. Efficacy and patient-related outcomes were not focused. The patients reported a high degree of acceptability of the methodology. The GPs reported the BI to be feasible to implement within a busy practice and to represent a new and improved instrument for communication with MOH patients. The BI requires further testing in a randomised controlled trial (RCT) in order to provide evidence of efficacy.
Conclusion
This feasibility study will be used to improve the BI for MOH and the design of a cluster-RCT.
Trial registration
ClinicalTrials.gov: NCT01078012 (Initially registered as controlled efficacy trial but changed to observational study).
doi:10.1186/1756-0500-7-165
PMCID: PMC3994567  PMID: 24646429
Chronic headache; Medication-overuse headache; Migraine; Brief intervention; General practice; Severity of dependence scale; Feasibility study; Pilot study
2.  Neuroimaging for the Evaluation of Chronic Headaches 
Executive Summary
Objective
The objectives of this evidence based review are:
i) To determine the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) scans in the evaluation of persons with a chronic headache and a normal neurological examination.
ii) To determine the comparative effectiveness of CT and MRI scans for detecting significant intracranial abnormalities in persons with chronic headache and a normal neurological exam.
iii) To determine the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Clinical Need: Condition and Target Population
Headaches disorders are generally classified as either primary or secondary with further sub-classifications into specific headache types. Primary headaches are those not caused by a disease or medical condition and include i) tension-type headache, ii) migraine, iii) cluster headache and, iv) other primary headaches, such as hemicrania continua and new daily persistent headache. Secondary headaches include those headaches caused by an underlying medical condition. While primary headaches disorders are far more frequent than secondary headache disorders, there is an urge to carry out neuroimaging studies (CT and/or MRI scans) out of fear of missing uncommon secondary causes and often to relieve patient anxiety.
Tension type headaches are the most common primary headache disorder and migraines are the most common severe primary headache disorder. Cluster headaches are a type of trigeminal autonomic cephalalgia and are less common than migraines and tension type headaches. Chronic headaches are defined as headaches present for at least 3 months and lasting greater than or equal to 15 days per month. The International Classification of Headache Disorders states that for most secondary headaches the characteristics of the headache are poorly described in the literature and for those headache disorders where it is well described there are few diagnostically important features.
The global prevalence of headache in general in the adult population is estimated at 46%, for tension-type headache it is 42% and 11% for migraine headache. The estimated prevalence of cluster headaches is 0.1% or 1 in 1000 persons. The prevalence of chronic daily headache is estimated at 3%.
Neuroimaging
Computed Tomography
Computed tomography (CT) is a medical imaging technique used to aid diagnosis and to guide interventional and therapeutic procedures. It allows rapid acquisition of high-resolution three-dimensional images, providing radiologists and other physicians with cross-sectional views of a person’s anatomy. CT scanning poses risk of radiation exposure. The radiation exposure from a conventional CT scanner may emit effective doses of 2-4mSv for a typical head CT.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used to aid diagnosis but unlike CT it does not use ionizing radiation. Instead, it uses a strong magnetic field to image a person’s anatomy. Compared to CT, MRI can provide increased contrast between the soft tissues of the body. Because of the persistent magnetic field, extra care is required in the magnetic resonance environment to ensure that injury or harm does not come to any personnel while in the environment.
Research Questions
What is the effectiveness of CT and MRI scanning in the evaluation of persons with a chronic headache and a normal neurological examination?
What is the comparative effectiveness of CT and MRI scanning for detecting significant intracranial abnormality in persons with chronic headache and a normal neurological exam?
What is the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Research Methods
Literature Search
Search Strategy
A literature search was performed on February 18, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January, 2005 to February, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Systematic reviews, randomized controlled trials, observational studies
Outpatient adult population with chronic headache and normal neurological exam
Studies reporting likelihood ratio of clinical variables for a significant intracranial abnormality
English language studies
2005-present
Exclusion Criteria
Studies which report outcomes for persons with seizures, focal symptoms, recent/new onset headache, change in presentation, thunderclap headache, and headache due to trauma
Persons with abnormal neurological examination
Case reports
Outcomes of Interest
Primary Outcome
Probability for intracranial abnormality
Secondary Outcome
Patient relief from anxiety
System service use
System costs
Detection rates for significant abnormalities in MRI and CT scans
Summary of Findings
Effectiveness
One systematic review, 1 small RCT, and 1 observational study met the inclusion and exclusion criteria. The systematic review completed by Detsky, et al. reported the likelihood ratios of specific clinical variables to predict significant intracranial abnormalities. The RCT completed by Howard et al., evaluated whether neuroimaging persons with chronic headache increased or reduced patient anxiety. The prospective observational study by Sempere et al., provided evidence for the pre-test probability of intracranial abnormalities in persons with chronic headache as well as minimal data on the comparative effectiveness of CT and MRI to detect intracranial abnormalities.
Outcome 1: Pre-test Probability.
The pre-test probability is usually related to the prevalence of the disease and can be adjusted depending on the characteristics of the population. The study by Sempere et al. determined the pre-test probability (prevalence) of significant intracranial abnormalities in persons with chronic headaches defined as headache experienced for at least a 4 week duration with a normal neurological exam. There is a pre-test probability of 0.9% (95% CI 0.5, 1.4) in persons with chronic headache and normal neurological exam. The highest pre-test probability of 5 found in persons with cluster headaches. The second highest, that of 3.7, was reported in persons with indeterminate type headache. There was a 0.75% rate of incidental findings.
Likelihood ratios for detecting a significant abnormality
Clinical findings from the history and physical may be used as screening test to predict abnormalities on neuroimaging. The extent to which the clinical variable may be a good predictive variable can be captured by reporting its likelihood ratio. The likelihood ratio provides an estimate of how much a test result will change the odds of having a disease or condition. The positive likelihood ratio (LR+) tells you how much the odds of having the disease increases when a test is positive. The negative likelihood ratio (LR-) tells you how much the odds of having the disease decreases when the test is negative.
Detsky et al., determined the likelihood ratio for specific clinical variable from 11 studies. There were 4 clinical variables with both statistically significant positive and negative likelihood ratios. These included: abnormal neurological exam (LR+ 5.3, LR- 0.72), undefined headache (LR+ 3.8, LR- 0.66), headache aggravated by exertion or valsalva (LR+ 2.3, LR- 0.70), and headache with vomiting (LR+ 1.8, and LR- 0.47). There were two clinical variables with a statistically significant positive likelihood ratio and non significant negative likelihood ratio. These included: cluster-type headache (LR+ 11, LR- 0.95), and headache with aura (LR+ 12.9, LR- 0.52). Finally, there were 8 clinical variables with both statistically non significant positive and negative likelihood ratios. These included: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, and migraine type headache.
Outcome 2: Relief from Anxiety
Howard et al. completed an RCT of 150 persons to determine if neuroimaging for headaches was anxiolytic or anxiogenic. Persons were randomized to receiving either an MRI scan or no scan for investigation of their headache. The study population was stratified into those persons with a Hospital Anxiety and Depression scale (HADS) > 11 (the high anxiety and depression group) and those < 11 (the low anxiety and depression) so that there were 4 groups:
Group 1: High anxiety and depression, no scan group
Group 2: High anxiety and depression, scan group
Group 3: Low anxiety and depression, no scan group
Group 4: Low anxiety and depression, scan group
Anxiety
There was no evidence for any overall reduction in anxiety at 1 year as measured by a visual analogue scale of ‘level of worry’ when analysed by whether the person received a scan or not. Similarly, there was no interaction between anxiety and depression status and whether a scan was offered or not on patient anxiety. Anxiety did not decrease at 1 year to any statistically significant degree in the high anxiety and depression group (HADS positive) compared with the low anxiety and depression group (HADS negative).
There are serious methodological limitations in this study design which may have contributed to these negative results. First, when considering the comparison of ‘scan’ vs. ‘no scan’ groups, 12 people (16%) in the ‘no scan group’ actually received a scan within the follow up year. If indeed scanning does reduce anxiety then this contamination of the ‘no scan’ group may have reduced the effect between the groups results resulting in a non significant difference in anxiety scores between the ‘scanned’ and the ‘no scan’ group. Second, there was an inadequate sample size at 1 year follow up in each of the 4 groups which may have contributed to a Type II statistical error (missing a difference when one may exist) when comparing scan vs. no scan by anxiety and depression status. Therefore, based on the results and study limitations it is inconclusive as to whether scanning reduces anxiety.
Outcome 3: System Services
Howard et al., considered services used and system costs a secondary outcome. These were determined by examining primary care case notes at 1 year for consultation rates, symptoms, further investigations, and contact with secondary and tertiary care.
System Services
The authors report that the use of neurologist and psychiatrist services was significantly higher for those persons not offered as scan, regardless of their anxiety and depression status (P<0.001 for neurologist, and P=0.033 for psychiatrist)
Outcome 4: System Costs
System Costs
There was evidence of statistically significantly lower system costs if persons with high levels of anxiety and depression (Hospital Anxiety and Depression Scale score >11) were provided with a scan (P=0.03 including inpatient costs, and 0.047 excluding inpatient costs).
Comparative Effectiveness of CT and MRI Scans
One study reported the detection rate for significant intracranial abnormalities using CT and MRI. In a cohort of 1876 persons with a non acute headache defined as any type of headache that had begun at least 4 weeks before enrolment Sempere et al. reported that the detection rate was 19/1432 (1.3%) using CT and 4/444 (0.9%) using MRI. Of 119 normal CT scans 2 (1.7%) had significant intracranial abnormality on MRI. The 2 cases were a small meningioma, and an acoustic neurinoma.
Summary
The evidence presented can be summarized as follows:
Pre-test Probability
Based on the results by Sempere et al., there is a low pre-test probability for intracranial abnormalities in persons with chronic headaches and a normal neurological exam (defined as headaches experiences for a minimum of 4 weeks). The Grade quality of evidence supporting this outcome is very low.
Likelihood Ratios
Based on the systematic review by Detsky et al., there is a statistically significant positive and negative likelihood ratio for the following clinical variables: abnormal neurological exam, undefined headache, headache aggravated by exertion or valsalva, headache with vomiting. Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al. there is a statistically significant positive likelihood ratio but non statistically significant negative likelihood ratio for the following clinical variables: cluster headache and headache with aura. The Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al., there is a non significant positive and negative likelihood ratio for the following clinical variables: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, migraine type headache. The Grade quality of evidence supporting this outcome is very low.
Relief from Anxiety
Based on the RCT by Howard et al., it is inconclusive whether neuroimaging scans in persons with a chronic headache are anxiolytic. The Grade quality of evidence supporting this outcome is low.
System Services
Based on the RCT by Howard et al. scanning persons with chronic headache regardless of their anxiety and/or depression level reduces service use. The Grade quality of evidence is low.
System Costs
Based on the RCT by Howard et al., scanning persons with a score greater than 11 on the High Anxiety and Depression Scale reduces system costs. The Grade quality of evidence is moderate.
Comparative Effectiveness of CT and MRI Scans
There is sparse evidence to determine the relative effectiveness of CT compared with MRI scanning for the detection of intracranial abnormalities. The Grade quality of evidence supporting this is very low.
Economic Analysis
Ontario Perspective
Volumes for neuroimaging of the head i.e. CT and MRI scans, from the Ontario Health Insurance Plan (OHIP) data set were used to investigate trends in the province for Fiscal Years (FY) 2004-2009.
Assumptions were made in order to investigate neuroimaging of the head for the indication of headache. From the literature, 27% of all CT and 13% of all MRI scans for the head were assumed to include an indication of headache. From that same retrospective chart review and personal communication with the author 16% of CT scans and 4% of MRI scans for the head were for the sole indication of headache. From the Ministry of Health and Long-Term Care (MOHLTC) wait times data, 73% of all CT and 93% of all MRI scans in the province, irrespective of indication were outpatient procedures.
The expenditure for each FY reflects the volume for that year and since volumes have increased in the past 6 FYs, the expenditure has also increased with a pay-out reaching 3.0M and 2.8M for CT and MRI services of the head respectively for the indication of headache and a pay-out reaching 1.8M and 0.9M for CT and MRI services of the head respectively for the indication of headache only in FY 08/09.
Cost per Abnormal Finding
The yield of abnormal finding for a CT and MRI scan of the head for the indication of headache only is 2% and 5% respectively. Based on these yield a high-level estimate of the cost per abnormal finding with neuroimaging of the head for headache only can be calculated for each FY. In FY 08/09 there were 37,434 CT and 16,197 MRI scans of the head for headache only. These volumes would generate a yield of abnormal finding of 749 and 910 with a CT scan and MRI scan respectively. The expenditure for FY 08/09 was 1.8M and 0.9M for CT and MRI services respectively. Therefore the cost per abnormal finding would be $2,409 for CT and $957 for MRI. These cost per abnormal finding estimates were limited because they did not factor in comparators or the consequences associated with an abnormal reading or FNs. The estimates only consider the cost of the neuroimaging procedure and the yield of abnormal finding with the respective procedure.
PMCID: PMC3377587  PMID: 23074404
3.  Medication-overuse headache: a review 
Journal of Pain Research  2014;7:367-378.
Medication-overuse headache (MOH) is a worldwide health problem with a prevalence of 1%–2%. It is a severe form of headache where the patients often have a long history of headache and of unsuccessful treatments. MOH is characterized by chronic headache and overuse of different headache medications. Through the years, withdrawal of the overused medication has been recognized as the treatment of choice. However, currently, there is no clear consensus regarding the optimal strategy for management of MOH. Treatment approaches are based on expert opinion rather than scientific evidence. This review focuses on aspects of epidemiology, diagnosis, pathogenesis, prevention, and treatment of MOH. We suggest that information and education about the risk of MOH is important since the condition is preventable. Most patients experience reduction of headache days and intensity after successful treatment. The first step in the treatment of MOH should be carried out in primary care and focus primarily on withdrawal, leaving prophylactic medication to those who do not manage primary detoxification. For most patients, a general practitioner can perform the follow-up after detoxification. More complicated cases should be referred to neurologists and headache clinics. Patients suffering with MOH have much to gain by an earlier treatment-focused approach, since the condition is both preventable and treatable.
doi:10.2147/JPR.S46071
PMCID: PMC4079825  PMID: 25061336
medication-overuse headache; migraine; chronic headache; dependence
4.  GPs’ experiences with brief intervention for medication-overuse headache: a qualitative study in general practice 
The British Journal of General Practice  2014;64(626):e525-e531.
Background
Medication-overuse headache (MOH) is common in the general population, and most patients are managed in primary health care. Brief Intervention (BI) has been used as a motivational technique for patients with drug and alcohol overuse, and may a have role in the treatment of MOH.
Aim
To explore GPs’ experiences using BI in the management of patients with MOH.
Design and setting
Qualitative study in Norwegian general practice.
Method
Data were collected through four focus group interviews with 22 GPs who participated in an intervention study on BI for MOH. Systematic text condensation was used to analyse transcripts from the focus group interviews.
Results
The GPs experienced challenges when trying to convince patients that the medication they used to treat and prevent headache could cause headache, but labelling MOH as a diagnosis opened up a space for change. GPs were able to use BI within the scope of a regular consultation, and they thought that the structured approach had a potential to change patients’ views about their condition and medication use. Being diagnosed with medication overuse could bring about feelings of guilt in patients, and GPs emphasised that a good alliance with the patient was necessary for successful change using BI to manage MOH.
Conclusion
GPs experience BI as a feasible strategy to treat MOH, and the technique relies on a good alliance between the doctor and patient. When using BI, GPs must be prepared to counter patients’ misconceptions about medication used for headache.
doi:10.3399/bjgp14X681313
PMCID: PMC4141608  PMID: 25179065
headache disorder, secondary; analgesic/adverse effects; primary care, qualitative study
5.  Prevalence of medication overuse headache in an interdisciplinary pain clinic 
Background
Medication overuse headache (MOH) has been recognized as an important problem in headache patients although the pathophysiological mechanisms remain unclear. The diagnosis of MOH is based on clinical characteristics defined by the International Headache Society. The aim was the evaluation of the diagnostic criteria of MOH in a mixed population of chronic pain patients to gain information about the prevalence and possible associations with MOH.
Methods
Data of all patients referred to the interdisciplinary pain clinic at the University Hospital of Zurich between September 2005 and December 2007 were retrospectively analyzed. Demographic data (age, sex, history of migration), as well as data about duration of pain disease, category of pain disease (neurological, psychiatric, rheumatologic, other), use of medication, history of trauma, and comorbidity of depression and anxiety have been collected.
Results
Totally 178 of 187 consecutive chronic pain patients were included in the study. A total of 138 patients (78%) used analgesics on 15 or more days per month. Chronic headache was more prevalent among patients with analgesic overuse (39.8%) than without analgesic overuse (18%). The prevalence of MOH was 29%. The odds ratio (OR) for a patient with medication overuse to have chronic headache was 13.1 if he had a history of primary headache, compared to a patient without a primary headache syndrome. Furthermore, history of headache (OR 2.5, CI [1.13;5.44]), history of migration (OR 2.9, CI [1.31;6.32]) and comorbid depression (OR 3.5, CI [1.46;8.52]) were associated with overuse of acute medication, in general.
Conclusions
Primary headaches have a high risk for chronification in patients overusing analgesics for other pain disorders. Whereas history of headache, history of migration and comorbidity of depression are independentely associated with analgesic overuse in this group of patients.
doi:10.1186/1129-2377-14-4
PMCID: PMC3606964  PMID: 23565761
Medication overuse; Headache; Interdisciplinary pain management; Chronic pain
6.  Preliminary results of a withdrawal and detoxification therapeutic regimen in patients with probable chronic migraine and probable medication overuse headache 
The Journal of Headache and Pain  2005;6(4):334-337.
Chronic migraine (CM) is an invalidating condition affecting a significant population of headache sufferers, frequently associated with medication overuse headache (MOH). Controlled trials and guidelines for the treatment of MOH are currently not available. We studied the efficacy of a therapeutic regimen for the withdrawal of the overused drug and detoxification in a sample of patients suffering from probable CM and probable MOH during admission in eight hospitals of Piemonte–Liguria–Valle d’Aosta. Fifty patients, 42 females (84%) and 8 males (16%), mean age at observation 50.66±13.08 years, affected by probable CM and daily medication overuse following IHS diagnostic criteria were treated as inpatients or in a day hospital. Headache index (HI) and daily drug intake (DDI) were used for evaluating the severity of headache and medication overuse. The patients were treated by abrupt discontinuation of the overused drug and by a therapeutic protocol including i.v. hydration, dexamethasone, metoclopramide and benzodiazepines for 7–10 days. Prophylactic medication was started immediately after admission. Analgesics or triptans were used under medical control only in cases of severe rebound headache. Diagnostic protocol included routine blood tests (at admission and at discharge), dosage of B12 and folic acid. Patients underwent follow-up controls one, three and six months after discharge. The initial diagnosis was probable CM in almost all patients included in the study (41 patients); in nine patients the diagnosis was not specified (coded only as CDH). The overused medications were simple analgesics in 17 cases (34%), combination analgesics in 19 cases (38%), triptans alone or with analgesics in 13 cases (26%) and ergotamine in 2 cases (4%). We collected data from 39 patients at first follow–up (1 month), 32 after 3 months and 14 after 6 months. Mean HI was 0.91 at admission, 0.22 at discharge, 0.38 after 30 days, 0.46 after 3 months and 0.48 after 6 months. Mean DDI was 2.80 at admission, 0.39 at discharge, 0.41 after 1 month, 0.52 after 3 months and 0.59 after 6 months. These results are on average positive and tend to remain stable with time. Although preliminary and obtained on a limited number of patients at 6–month follow–up, our results seem to be encouraging about the use of the proposed therapeutic protocol.
doi:10.1007/s10194-005-0225-7
PMCID: PMC3452038  PMID: 16362704
Chronic daily headache; Chronic migraine; Medication overuse; Detoxification
7.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
8.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
9.  Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial 
The Journal of Headache and Pain  2012;13(8):677-684.
Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena’s Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake (p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (−41 %, p < 0.01) and to improve the quality of life (p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary findings.
doi:10.1007/s10194-012-0490-1
PMCID: PMC3484259  PMID: 23070400
Medication overuse headache (MOH); Treatment; Nabilone; Cannabinoid; Migraine
10.  Medication overuse headache: a critical review of end points in recent follow-up studies 
The Journal of Headache and Pain  2010;11(5):373-377.
No guidelines for performing and presenting the results of studies on patients with medication overuse headache (MOH) exist. The aim of this study was to review long-term outcome measures in follow-up studies published in 2006 or later. We included MOH studies with >6 months duration presenting a minimum of one predefined end point. In total, nine studies were identified. The 1,589 MOH patients (22% men) had an overall mean frequency of 25.3 headache days/month at baseline. Headache days/month at the end of follow-up was reported in six studies (mean 13.8 days/month). The decrease was more pronounced for studies including patients with migraine only (−14.6 days/month) compared to studies with the original diagnoses of migraine and tension-type headache (−9.2 days/month). Six studies reported relapse rate (mean of 26%) and/or responder rate (mean of 28%). Medication days/month and change in headache index at the end of follow-up were reported in only one and two of nine studies, respectively. The present review demonstrated a lack of uniform end points used in recently published follow-up studies. Guidelines for presenting follow-up data on MOH are needed and we propose end points such as headache days/month, medication days/month, relapse rate and responder rate defined as ≥50% reduction of headache frequency and/or headache index from baseline.
doi:10.1007/s10194-010-0221-4
PMCID: PMC3452270  PMID: 20473701
Medication overuse headache; Follow-up; Outcome parameters; Relapse rate; Responders
11.  Holding on to the indispensable medication –A grounded theory on medication use from the perspective of persons with medication overuse headache 
Background
Medication overuse headache (MOH) is a chronic headache disorder, caused by overuse of acute medication. To date, it remains unclear why some people overuse these medications. The aim of this qualitative study was to explore how individuals with MOH use medications and other strategies to manage headaches in their daily lives, and their thoughts about their own use of acute medication. Our intention was to develop a theoretical model about the development of MOH, from the perspective of those with MOH.
Methods
Data collection and analysis were conducted according to grounded theory methodology. The participants were recruited via newspaper advertisements. Fourteen persons with MOH were interviewed in individual qualitative interviews.
Results
The basic process leading to medication overuse was holding on to the indispensable medication. The acute medication was indispensable to the participants because they perceived it as the only thing that could prevent headaches from ruining their lives. The participants perceived headaches as something that threatened to ruin their lives. As a result, they went to great lengths trying to find ways to manage it. They tried numerous strategies. However, the only strategy actually perceived as effective was the use of acute medication and they eventually became resigned to the idea that it was the only effective aid. The acute medication thus became indispensable. Their general intention was to use as little medication as possible but they found themselves compelled to medicate frequently to cope with their headaches. They did not like to think about their medication use and sometimes avoided keeping track of the amount used.
Conclusions
This qualitative study adds understanding to the process via which MOH develops from the perspective of those having MOH. Such knowledge may help bridge the gap between the perspectives of patients and health-care professionals.
doi:10.1186/1129-2377-14-43
PMCID: PMC3671143  PMID: 23697986
Headache; Medication use; Medication overuse headache; Qualitative study; Grounded theory; Patient perspective
12.  An electronic diary on a palm device for headache monitoring: a preliminary experience 
The Journal of Headache and Pain  2012;13(7):537-541.
Patients suffering from headache are usually asked to use charts to allow monitoring of their disease. These diaries, providing they are regularly filled in, become crucial in the diagnosis and management of headache disorders because they provide further information on attack frequency and temporal pattern, drug intake, trigger factors, and short-/long-term responses to treatment. Electronic tools could facilitate diary monitoring and thus the management of headaches. Medication overuse headache (MOH) is a chronic and disabling condition that can be treated by withdrawing the overused drug(s) and adopting specific approaches that focus on the development of a close doctor–patient relationship in the post-withdrawal phase. Although the headache diary is, in this context, an essential tool for the constant, reliable monitoring of these patients to prevent relapses, very little is known about the applicability of electronic diaries in MOH patients. The purpose of this study was to evaluate the acceptability of and patient compliance with an electronic headache diary (palm device) as compared with a traditional diary chart in a group of headache inpatients with MOH. A palm diary device, developed in accordance with the ICHD-II criteria, was given to 85 MOH inpatients during the detoxification phase. On the first day of hospitalization, the patients were instructed in the use of the diary and were then required to fill it in daily for the following 7 days. Data on the patients’ opinions on the electronic diary and the instructions given, its screen and layout, as well as its convenience and ease of use, in comparison with the traditional paper version, were collected using a numerical rating scale. A total of 504 days with headache were recorded in both the electronic and the traditional headache diaries simultaneously. The level of patient compliance was good. The patients appreciated the electronic headache diary, deeming it easy to understand and to use (fill in); most of the patients rated the palm device handier than the traditional paper version.
doi:10.1007/s10194-012-0473-2
PMCID: PMC3444534  PMID: 22842873
Medication overuse headache; Electronic diary; Headache; Feasibility; Compliance
13.  Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls (DNIC) in dura-sensitive medullary dorsal horn neurons 
Overuse of medications used to treat migraine headache can produce a chronic daily headache, termed medication overuse headache (MOH). Although “overuse” of opioids, triptans, and over-the-counter analgesics can all produce MOH, the neuronal mechanisms remain unknown. Headache pain is likely to be produced by stimulation of primary afferent neurons that innervate the intracranial vasculature and the resulting activation of medullary dorsal horn (MDH) neurons. The present study compared the receptive field properties of MDH dura sensitive neurons in rats treated with morphine to those given vehicle. Animals were implanted with osmotic mini-pumps or pellets for sustained subcutaneous administration of morphine or vehicle 6–7 days prior to recording from dura-sensitive neurons. Electrical and mechanical activation thresholds from the dura were significantly lower in chronic morphine treated animals when compared to vehicle controls. In addition, sustained morphine increased the cutaneous receptive field sizes. The presence of diffuse noxious inhibitory controls (DNIC) was examined by placing the tail in 55°C water during concomitant noxious thermal stimulation of the cutaneous receptive field, usually located in the ophthalmic region. The DNIC stimulus produced significant inhibition of heat-evoked activity in vehicle, but not chronic morphine treated animals. Inactivation of the rostral ventromedial medulla (RVM) with 4% lidocaine reinstated DNIC in chronic morphine treated animals. These results are consistent with studies demonstrating a loss of DNIC in patients that suffer from chronic daily headache and may partially explain why overuse of medication used to treat migraine can induce headaches.
doi:10.1523/JNEUROSCI.3623-09.2009
PMCID: PMC3177943  PMID: 20016098
Medication overuse headache; trigeminal nucleus; morphine; opioid; DNIC; RVM
14.  A CARE pathway in medication–overuse headache: the experience of the Headache Centre in Pavia 
The Journal of Headache and Pain  2005;6(4):307-309.
Medication–overuse headache (MOH) is one of the headache forms that most frequently prompts patients to consult a specialist headache centre. The prevaence of this form in the general population is approximately 1–2%. Around 40% of patients seen at headache centres present with a chronic form of headache and 80% of this chronic headache patients make excessive use of symptomatic drugs. MOH shows a clinical improvement, accompained by a reduction in the consumption of analgesic drugs, if patients are submitted to detoxification therapy. But detoxification is only the first stage in a long and complex course of care and global approach demands adequate follow–up visit to prevent early relapses. At the Headache Centre of the C. Mondino Institute of Neurologt in Pavia, a course of care (CARE) has been developed for the complente management of patients with MOH both during Hospitalization and durimg the subsequent follow–up period. CARE IS designed to trace the clinical, psychopathological and pharmacological profile of MOH in the short–, medium– and long–term; to look for factors possibility predictive of relapse; to assess the direct costs linked to overuse–headache in the year leading up to and following detoxification; and to evaluate disability, in terms of working days lost, before and after detoxification.
doi:10.1007/s10194-005-0216-8
PMCID: PMC3452024  PMID: 16362695
Medication–overuse headache; Care pathway; Management
15.  Probable medications overuse headaches: validation of a brief easy-to-use screening tool in a headache centre 
Background
To validate a rapid questionnaire as a screening tool, because application of the diagnostic revised criteria of the ICHD-II for medication overuse headache (MOH) requires experience for the physician and is time-consuming.
Methods
ICHD-II criteria for probable MOH (pMOH) were transformed in questions formulated in such a way that they could be self-administered, easily understood, and quickly filled out. We compared this questionnaire to the gold standard: the diagnosis made by headache specialists, based on the the ICHD-II criteria. Patients who were consulting for pMOH or migraine for the first time were consecutively included. As validity indicators, we calculated sensitivity, specificity, positive and negative predictive values of the items.
Results
Seventy-nine patients were screened, 77 included, 2 female patients excluded. Forty-two patients have been considered as suffering from pMOH, 35 patients suffered from migraine without medication overuse. The association of the question “do you take a treatment for attacks more than 10 days per month” and the question “is this intake on a regular basis?” had a sensitivity of 95.2% and a specificity of 80%.
Conclusion
This screening tool can detect pMOH with a sensitivity that could be of interest to screen patients in clinical practice and to pre-include patients for research as epidemiological studies.
doi:10.1186/1129-2377-14-81
PMCID: PMC3850931  PMID: 24088386
Medications overuse headaches; Screening tool; Validation; Questionnaire; Sensitivity; Specificity
16.  Application of ICHD-II Criteria in a Headache Clinic of China 
PLoS ONE  2012;7(12):e50898.
Background
China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II).
Methods and Results
Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2nd decade for females and the 1st decade for males.
Conclusions/Significance
This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.
doi:10.1371/journal.pone.0050898
PMCID: PMC3519829  PMID: 23239993
17.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
18.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
19.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.
doi:10.1007/s10194-011-0388-3
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
20.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.
doi:10.1007/s10194-011-0388-3
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
21.  Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: design of a randomised clinical trial 
Background
Patients with Chronic Tension Type Headache (CTTH) report functional and emotional impairments (loss of workdays, sleep disturbances, emotional well-being) and are at risk for overuse of medication. Manual therapy may improve symptoms through mobilisation of the spine, correction of posture, and training of cervical muscles.
We present the design of a randomised clinical trial (RCT) evaluating the effectiveness of manual therapy (MT) compared to usual care by the general practitioner (GP) in patients with CTTH.
Methods and design
Patients are eligible for participation if they present in general practice with CTTH according to the classification of the International Headache Society (IHS).
Participants are randomised to either usual GP care according to the national Dutch general practice guidelines for headache, or manual therapy, consisting of mobilisations (high- and low velocity techniques), exercise therapy for the cervical and thoracic spine and postural correction. The primary outcome measures are the number of headache days and use of medication. Secondary outcome measures are severity of headache, functional status, sickness absence, use of other healthcare resources, active cervical range of motion, algometry, endurance of the neckflexor muscles and head posture. Follow-up assessments are conducted after 8 and 26 weeks.
Discussion
This is a pragmatic trial in which interventions are offered as they are carried out in everyday practice. This increases generalisability of results, but blinding of patients, GPs and therapists is not possible.
The results of this trial will contribute to clinical decision making of the GP regarding referral to manual therapy in patients with chronic tension headache.
doi:10.1186/1471-2474-10-21
PMCID: PMC2662792  PMID: 19216763
22.  Evaluating integrated headache care: a one-year follow-up observational study in patients treated at the Essen headache centre 
BMC Neurology  2011;11:124.
Background
Outpatient integrated headache care was established in 2005 at the Essen Headache Centre in Germany. This paper reports outcome data for this approach.
Methods
Patients were seen by a neurologist for headache diagnosis and recommendation for drug treatment. Depending on clinical needs, patients were seen by a psychologist and/or physical therapist. A 5-day headache-specific multidisciplinary treatment programme (MTP) was provided for patients with frequent or chronic migraine, tension type headache (TTH) and medication overuse headache (MOH). Subsequent outpatient treatment was provided by neurologists in private practice.
Results
Follow-up data on headache frequency and burden of disease were prospectively obtained in 841 patients (mean age 41.5 years) after 3, 6 and 12 months. At baseline mean headache frequency was 18.1 (SD = 1.6) days per month, compared to measurement at 1 year follow-up a mean reduction of 5.8 (SD = 11.9) headache days per month was observed in 486 patients (57.8%) after one year (TTH patients mean: -8.5 days per month; migraine mean: -3.2 days per month, patients with migraine and TTH mean: -5.9 days per month). A reduction in headache days ≥ 50% was observed in 306 patients (36.4%) independent of diagnosis, while headache frequency remains unchanged in 20.9% and increase in 21.3% of the patient.
Conclusion
Multidisciplinary outpatient headache centres offer an effective way to establish a three-tier treatment offer for difficult headache patients depending on clinical needs.
doi:10.1186/1471-2377-11-124
PMCID: PMC3203041  PMID: 21985562
23.  Medication–overuse headache: pathophysiological insights 
The Journal of Headache and Pain  2005;6(4):199-202.
Medication overuse headache (MOH) is a clinically important entity and it is now well documented that the regular use of acute symptomatic medication by people with migraine or tensiontype headache increases the risk of aggravation of the primary headache. MOH is one of the most common causes of chronic migraine–like syndrome. Because of easy availability and low expense, the greatest problem appears to be associated with barbiturate–containing combination analgesics and over–the–counter caffeine–containing combination analgesics. Even though triptan overuse headache is not encountered with great frequency, all triptans should be considered potential inducers of MOH. There are several different theories regarding the aetiology of MOH, including: (i) central sensitisation from repetitive activation of nociceptive pathways; (ii) a direct effect of the medication on the capacity of the brain to inhibit pain; (iii) a decrease in blood serotonin due to repetitive medication administration with alteration of serotonin receptors; (iv) cellular adaptation in the brain; and (v) changes in the periaqueductal grey matter. The principal approach to management of MOH is built around cessation of overused medication. Without discontinuation of the offending medication, improvement is almost impossible to attain. Thus, the best management advice is to raise awareness and strive for prevention. In this article, we analyse also the possible mechanisms that underlie sensitisation in MOH by comparing these mechanisms with those reported for other forms of drug addiction.
doi:10.1007/s10194-005-0184-z
PMCID: PMC3452046  PMID: 16362663
Medication overuse headache; Migrane; Sensitization; Drug abuse; Obsessive behaviour compulsive
24.  The validity of questionnaire-based diagnoses: the third Nord-Trøndelag Health Study 2006–2008 
The Nord-Trøndelag Health Study (HUNT 3) performed in 2006–2008 is a replication of the cross-sectional survey from 1995 to 1997 (HUNT 2). The aim of the present study was to assess the sensitivity and specificity of questionnaire-based headache diagnoses using a personal interview by a neurologist as a gold standard. For the questionnaire-based status as headache sufferer, a sensitivity of 88%, a specificity of 86%, and a kappa statistic of 0.70 were found. Chronic headache, chronic tension-type headache (TTH), and medication overuse headache (MOH) were diagnosed with a specificity of ≥99%, and a kappa statistic of ≥0.73. Lower figures were found for the diagnoses of migraine and TTH. For individuals with headache ≥1 day per month, a sensitivity of 58% (migraine) and 96% (TTH), a specificity of 91 and 69%, and a kappa statistic of 0.54 and 0.44 were found, respectively. The specificity for migraine with aura was 95%. In conclusion, the HUNT 3-questionnaire is a valid tool for identifying headache sufferers, and diagnosing patients with chronic headache, including chronic TTH and MOH. The more moderate sensitivity for migraine and TTH makes the questionnaire-based diagnoses of migraine and TTH suboptimal for determining the prevalence. However, the high specificity of the questionnaire-based diagnosis of migraine, in particular for migraine with aura, makes the questionnaire a valid tool for diagnosing patients with migraine for genetic studies.
doi:10.1007/s10194-009-0174-7
PMCID: PMC3452179  PMID: 19946790
Headache; Migraine; Questionnaire; Survey; Population
25.  Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): a prospective, randomized, open-label trial 
Background
The aim of this study was to compare the effectiveness of an educational strategy (advice to withdraw the overused medication/s) with that of two structured pharmacological detoxification programmes in patients with complicated medication overuse headache (MOH) plus migraine.
Methods
One hundred and thirty-seven complicated MOH patients participated in the study. MOH was defined as complicated in patients presenting at least one of the following: a) a diagnosis of co-existent and complicating medical illnesses; b) a current diagnosis of mood disorder, anxiety disorder, eating disorder, or substance addiction disorder; c) relapse after previous detoxification treatment; d) social and environmental problems; e) daily use of multiple doses of symptomatic medications. Group A (46 patients) received only intensive advice to withdraw the overused medication/s. Group B (46 patients) underwent a standard detoxification programme as outpatients (advice + steroids + preventive treatment). Group C (45 patients) underwent a standard inpatient withdrawal programme (advice + steroids + fluid replacement and antiemetics preventive treatment). Withdrawal therapy was considered successful if, after two months, the patient had reverted to an intake of NSAIDs lower than 15 days/month or to an intake of other symptomatic medication/s lower than 10 days/month.
Results
Twenty-two patients failed to attend follow-up visits (11 in Group A, 9 in Group B, 2 in Group C, p < 0.03). Overall, we detoxified 70% of the whole cohort, 60.1% of the patients in Group A and in Group B, and 88.8% of those in Group C (p < 0.01).
Conclusions
Inpatient withdrawal is significantly more effective than advice alone or an outpatient strategy in complicated MOH patients.
doi:10.1186/1129-2377-14-10
PMCID: PMC3620000  PMID: 23565591
Medication overuse headache; Management; Migraine; Treatment

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