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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.  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
3.  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
4.  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
5.  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
6.  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
7.  Should we educate about the risks of medication overuse headache? 
Background
Medication-overuse headache (MOH) is caused by the regular use of medications to treat headache. There has been a lack of research into awareness of MOH. We distributed an electronic survey to undergraduate students and their contacts via social networking sites. Analgesic use, awareness of MOH, perceived change in behaviour following educational intervention about the risks of MOH and preferred terminology for MOH was evaluated.
Findings
485 respondents completed the questionnaire (41% having received healthcare training). 77% were unaware of the possibility of MOH resulting from regular analgesic use for headache. Following education about MOH, 80% stated they would reduce analgesic consumption or seek medical advice. 83% indicated that over the counter analgesia should carry a warning of MOH. The preferred terminology for MOH was painkiller-induced headache.
Conclusions
This study highlights the lack of awareness of MOH. Improved education about MOH and informative packaging of analgesics, highlighting the risks in preferred lay terminology (i.e. painkiller-induced headache), may reduce this iatrogenic morbidity and warrants further evaluation.
doi:10.1186/1129-2377-15-10
PMCID: PMC3942071  PMID: 24524380
Medication-overuse headache; Analgesia; Headache; Prevention; Education
8.  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
9.  Tension-type Headache With Medication Overuse: Pathophysiology and Clinical Implications 
Current pain and headache reports  2009;13(6):463-469.
Tension-type headache (TTH) is the most prevalent primary headache disorder. An important factor in the long-term prognosis of TTH is the overuse of acute medications used to treat headache. There are many reasons why patients with TTH overuse acute medications, including biobehavioral influences, dependency, and a lack of patient education. Chronic daily headache occurs in 4.1% of the general population, and chronic tension-type headache and medication overuse headache (MOH) occur in approximately 2.2% and 1.5%, respectively. A proper diagnosis is essential for the treatment of these patients. Treatment should include pathological considerations concerning TTH and MOH, which include peripheral and central mechanisms. Because TTH with MOH carries the worst prognosis, more clinical studies focusing on the complex interaction and treatments of TTH and MOH are needed.
PMCID: PMC4030319  PMID: 19889288
10.  Drug-dependence behaviour and outcome of medication-overuse headache after treatment 
The Journal of Headache and Pain  2012;13(8):653-660.
This study aimed at determining the causes of failure of the different proposed strategies to ensure improvement of medication-overuse headache (MOH) patients, since they have not been investigated so far, especially with regard to aspects related to cognitive and behavioural aspects of symptomatic drugs overused by them. One hundred and twenty in-patients, 82 females (68.3 %), median age 49 (42–56) years, affected by MOH were admitted to the study and treated with abrupt discontinuation of the medication overused, a 6-day in-patient detoxification regimen and an immediate start of personalized prophylactic treatment, then followed for 1 year. Leeds Dependence Questionnaire (LDQ), among all the clinical variables, was administered at baseline and at 1-year follow-up visit to assess substance dependence. Of the 120 patients enrolled, 68 (56.7 %) were successfully detoxified (Responder-group), while 52 (43.3 %) were not (Non-Responder-group). At baseline, the mean LDQ total score was slightly higher in the Non-Responder group than in the Responder group (12.08 ± 2.14 vs. 11.94 ± 1.98). Although this difference was not significant at baseline (p > 0.05), the LDQ total score was significantly different (p < 0.001) at the 1-year follow-up visit between the responder group (7.8 ± 2.3) and the Non-Responder group (12.1 ± 2.1). Moreover, the pattern of the responses of the patients in the responder group differed from that of the Non-Responder-group in the items relating to the compulsion to start, compulsion to continue, primacy of effect, constancy of state and cognitive set. The results showed that patients of the Non-Responder group showed a drug dependence pattern similar to that previously described in addicts. Conversely, in patients who positively responded to the procedure, drug-abuse behaviour seemed to be a consequence of chronic headache, reflecting the need for daily analgesic use to cope with everyday life.
doi:10.1007/s10194-012-0492-z
PMCID: PMC3484260  PMID: 23076353
Medication-overuse headache; Detoxification; Symptomatic drugs overuse; Drug dependence; Leeds Dependence Questionnaire
11.  Increased activity of serotonin uptake in platelets in medication overuse headache following regular intake of analgesics and triptans 
The Journal of Headache and Pain  2008;9(2):109-112.
We investigated the effect of chronic administration of different pain medications on the activity of the serotonin transporter (SERT) in patients with medication overuse headache (MOH). We measured the kinetic of platelet 5-HT uptake (maximal velocity, Vmax and the Michaelis–Menten constant, Km) in patients with overuse of triptans (tMOH, n = 15) or analgesics (aMOH, n = 14) before and after drug withdrawal, as well as in headache-free healthy subjects (n = 15) and patients with episodic migraine (EM, n = 16). Vmax was increased similarly in both, tMOH and aMOH compared to healthy subjects and patients with EM and normalized after withdrawal in parallel to the improvement of headache frequency. Average Km was similar in all groups at baseline and not affected by the withdrawal. The data demonstrate a transient increase of SERT activity in patients with analgesic and triptan induced MOH but do not allow to differentiate whether the increase of serotonin uptake is caused by regular intake of analgesics or triptans or is a consequence of frequent headache attacks.
doi:10.1007/s10194-008-0019-9
PMCID: PMC3476187  PMID: 18330504
Chronic migraine; Medication overuse headache; MOH; Serotonin uptake; Platelets
12.  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
13.  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
14.  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
15.  Acute treatment of headache 
The Journal of Headache and Pain  2006;7(5):355-359.
Effective acute treatment of headache begins with making an accurate diagnosis and ruling out secondary causes of headache. Once a primary headache is diagnosed, it is important to choose the right combination of behavioural therapy and acute care (abortive and symptomatic) therapy for each patient. Some patients may need preventive medication on a daily basis. If patients overuse acute medications and develop medication overuse headache (previously called analgesic rebound headache), they often seek medical attention due to the chronicity and/or intensity of their pain and resultant disability. For acute care of migraine, physicians should choose a triptan they know and expect to work. They should prescribe the dose and route of administration that will provide the most rapid and complete response to all the associated symptoms of migraine, in addition to the pain. The effectiveness of the 7 available triptans in early, double-blind, controlled trials is more similar than different. How and when to give them will be discussed. Treatment of cluster headache will be presented briefly.
doi:10.1007/s10194-006-0327-x
PMCID: PMC3468178  PMID: 17058043
Headache; Treatment; Acute care
16.  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
17.  Sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache 
The Journal of Headache and Pain  2012;13(4):281-290.
The objective of this study was to analyse sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache (MOH). A cross-sectional, population survey was conducted, in which 44,300 Swedes (≥15 years old) were interviewed over telephone. In total, 799 individuals had MOH. Of these, 47 % (n = 370) only used over-the-counter medications. During the last year, 46 % (n = 343) had made a headache-related visit to their physician and 14 % (n = 102) had visited a neurologist. Among individuals aged <30 years, the number of days/month with headache was greater than the number of days with medication use, whereas the opposite was true for those ≥30 years. Both the proportion using prophylactic medication and the proportion having consulted a neurologist were smaller among those who only had elementary school education than among those with higher education (p = 0.021 and p = 0.046). Those with a lower level of education also had a higher number of days/month with headache and with medication use than those with a higher educational level (p = 0.011 and p = 0.018). The MOH-sufferers have limited contacts with health-care and preventive measures thus need to include other actors as well. Particular efforts should be directed towards those with low educational levels, and more research on medication use in relation to age is required.
doi:10.1007/s10194-012-0432-y
PMCID: PMC3356474  PMID: 22427000
Headache; Medication-overuse headache; Epidemiology; Educational status; Medication use; Health-care contacts
18.  Topo–kinesthetic memory in chronic headaches. A new test for chronic patients: preliminary report 
The Journal of Headache and Pain  2005;6(6):448-454.
The objective of this study was to establish if chronic headaches with medication overuse can modify a topo–kinesthetic memory test. Nineteen patients with medication overuse headache (MOH), 13 patients with chronic tension–type headache (CTTH) without medication use and a group of "normal" subjects underwent a topo–kinesthetic memory test at T0 and after one month (T1); a control group of healthy volunteers was also tested to establish the baseline in our experimental setting. After one month, in the MOH patients there was a reduction of medication overuse from 3.3±2.65 to 1.1±2.23 (p<0.01), but no significant reduction in headache frequency and severity index, quality of life, anxiety and depression scores. The navigation time at T0 was 14.3±4.97, 27.9±10.12, 34.3±15.38 and 7.5±2.33, 10.1±2.95, 11.4±3.21 for control, MOH and CTTH with closed and open eyes, respectively (p<0.02). At T1, the MOH patients reached performances with open eyes similar to the healthy controls, while with closed eyes the navigation test reached times similar to those of CTTH patients. The topokinesthetic memory test seems both able to discriminate MOH and CTTH from healthy volunteers and to be related to pain scores but is not influenced by the use of drugs.
doi:10.1007/s10194-005-0248-0
PMCID: PMC3452299  PMID: 16388339
Topo–kinesthetic test; Chronic tension–type headache; MOH
19.  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
20.  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
21.  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
22.  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
23.  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
24.  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
25.  A narrative review on the management of medication overuse headache: the steep road from experience to evidence 
The Journal of Headache and Pain  2009;10(6):407-417.
The management of medication overuse headache (MOH) is based essentially on the withdrawal of the overused drug(s). Drug withdrawal is performed according to widely differing protocols, both within and across countries; therefore, therapeutic recommendations for the acute phase of detoxification vary considerably among studies. Basically, the aims of MOH management are: (a) to withdraw the overused drug(s); (b) to alleviate withdrawal symptoms by means of a bridge therapy, which includes pharmacological and non-pharmacological support, designed to help the patient to tolerate the withdrawal process; (c) to prevent relapse. Today, there is extensive debate over the best strategies for achieving these goals and the different aspects of this debate are discussed in this review. The authors searched for the best available evidence relating to the following questions: should medication withdrawal be abrupt or gradual? Should patients receive replacement therapy? What are the most effective therapeutic programmes for controlling withdrawal symptoms? Should replacement therapy be administered routinely or as rescue therapy? Should preventive treatment be started before, during or after withdrawal? What are the most effective preventive treatments? Should patients be managed through inpatient or outpatient withdrawal programmes? What is the best approach to adopt in preventing relapses? Treatment of MOH is a difficult challenge, but may be very rewarding. Although there is still a lack of high-quality studies providing evidence-based answers to the many specific questions it raises, neurologists need to know that the combination of education with a rational use of selected therapeutic strategies may be beneficial to people with chronic headache and help to relieve their suffering.
doi:10.1007/s10194-009-0159-6
PMCID: PMC3476213  PMID: 19802522
Medication overuse headache; Therapy; Management; MOH; Review

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