Clinical Aspects of Medication Overuse Headaches

Medication overuse headache (MOH) is a subset of chronic daily headache, occurring from overuse of 1 or more classes of migraine abortive medication. Acetaminophen, combination analgesics (caffeine combinations), opioids, barbiturates (butalbital), non‐steroidal anti‐inflammatory drugs, and triptans are the main classes of drugs implicated in the genesis of MOH. Migraine seems to be the most common diagnosis leading to MOH. The development of MOH is associated with both frequency of use of medication and behavioral predispositions. MOH is not a unitary concept. The distinction between simple (type 1) vs complex (type 2) forms is based on both the class of overused medication and behavioral factors, including psychopathology and psychological drug dependence. MOH is a challenging disorder causing decline in the quality of life and causing physical symptoms, such as daily and incapacitating headaches, insomnia, and non‐restorative sleep, as well as psychological distress and reduced functioning. MOH is associated with biochemical, structural, and functional brain changes. Relapse after detoxification is a challenge, but can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding previously overused medication, and providing psychological (cognitive‐behavioral) therapy.     

Medication overuse headache and chronic migraine in a specialized headache centre: field-testing proposed new appendix criteria

The classification subcommittee of the International Headache Society (IHS) has recently suggested revised criteria for medication overuse headache (MOH) and chronic migraine (CM). We field tested these revised criteria by applying them to the headache population at the Danish Headache Centre and compared the results with those using the current criteria. For CM we also tested two alternative criteria, one requiring > or = 4 migraine days/month and > or = 15 headache days/month, the second requiring > or = 15 headache days/month and > or = 50% migraine days. We included 969 patients with migraine or tension-type headache (TTH) among 1326 patients treated and dismissed in a 2-year period. Two hundred and eighty-five patients (30%) had TTH, 265 (27%) had migraine and 419 (43%) had mixed migraine and TTH. The current criteria for MOH classified 86 patients (9%) as MOH, 98 (10%) as probable MOH and 785 (81%) as not having MOH after a 2-month drug-free period. Using the appendix criteria, 284 patients (29%) were now classified as MOH, no patients as probable MOH and 685 (71%) as not having MOH. For CM only 16 patients (3%) fulfilled the current diagnostic criteria. This increased to 42 patients (7%) when we applied the appendix criteria. Using the less restrictive criteria of > or = 4 migraine days and > or = 15 headache days, 88 patients (14%) had CM, whereas the more restrictive criteria of > or = 15 headache days and > or = 50% migraine days resulted in 24 patients (4%) with CM. Our data suggest that the IHS has succeeded in choosing new criteria for CM which are neither too strict, nor too loose. For MOH, a shift to the appendix criteria will increase the number of MOH patients, but take into account the possibility of permanent changes in pain perception due to medication overuse and the possibility of a renewed effect of prophylactic drugs due to medication withdrawal. We therefore recommend the implementation of the appendix criteria for both MOH and CM into the main body of the International Classification of Headache Disorders.     

Medication overuse headache: clinical features predicting treatment outcome at 1-year follow-up

We present a prospective study of 240 patients with medication overuse headache (MOH) treated with drug withdrawal and prophylactic medications. At 1-year follow-up, 137 (57.1%) patients were without chronic headache and without medication overuse, eight (3.3%) patients did not improve after withdrawal and 95 (39.6%) relapsed developing recurrent overuse. Age at time of MOH diagnosis, regular use of benzodiazepines, frequency and Migraine Disability Assessment (MIDAS) score of chronic headache, age at onset of primary headache, frequency and MIDAS score of primary headache, ergotamine compound overuse and daily drug intake were significantly different between successfully and unsuccessfully treated patients. Multivariate analysis determined the frequency of primary headache disorder, ergotamine overuse and disability of chronic headache estimated by MIDAS as independent predictors of treatment efficacy at 1-year follow-up.     

Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period

OBJECTIVES: To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years. BACKGROUND: The acute treatment of migraine has substantially changed over the past 15 years, and therefore, the substances associated with MOH may have changed as well. METHODS: We randomly reviewed charts of subjects seen during the years of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since the criteria proposed by the second edition of the International Classification of Headache Disorders require causal attribution, demonstrated by improvement after withdrawal (and this was not assessed in this study), herein we refer to probable MOH (PMOH). We contrasted the substances associated with PMOH over the studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of interest. The proportions of subjects with a diagnosis of PMOH remained stable over the years, varying from 64% of all cases seen in the center in 1990, to 59.3% in 2005. We found a significant decrease in the relative frequency of probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001). The differences were not significant for opioid overuse headache. The relative frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001), simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute medications remains an important problem in the tertiary care arena, the substances associated with the overuse have dramatically changed over the past 15 years. Educational initiatives should emphasize that the newer specific acute migraine medications (triptans) may also be associated with PMOH.     

Dependence scores predict prognosis of medication overuse headache: a prospective cohort from the Akershus study of chronic headache

Medication overuse headache (MOH) is a chronic headache that is common in the general population. It has characteristics similar to drug dependence, and detoxification is established as the main treatment. The majority of MOH cases are in contact with general practitioners. Our objective was to investigate whether the Severity of Dependence Scale (SDS) score could be used as predictor for the prognosis of MOH in the general population. In a cross-sectional epidemiological survey, an age- and gender-stratified sample of 30,000 persons 30 to 44 years of age was recruited via a posted questionnaire. Those individuals with self-reported chronic headache (≥15 days per month) were interviewed by neurological residents at Akershus University Hospital, Oslo. The International Classification of Headache Disorders was used. Those with MOH were re-interviewed by telephone 2 to 3 years after the initial interview. SDS scores and medication information were collected at baseline and follow-up. The main outcomes were SDS scores, termination of MOH and chronic headache from baseline to follow-up. We found the predominant overused analgesics in this sample to be simple analgesics. At follow-up, 65% of participants no longer had medication overuse, and 37% had changed to episodic headache (<15 days per month). The SDS score at baseline successfully predicted improvement for primary MOH, but not secondary MOH. The SDS scores decreased slightly from baseline to follow-up in those who stopped medication overuse, but were still significantly higher than in subjects with chronic headache without medication overuse at baseline. We conclude that the SDS score can predict successful prognosis related to detoxification of primary MOH but not in secondary MOH.     

Controversy over the Classification of Medication-Overuse Headache

Medication-overuse headache (MOH) is a relatively common and impactful disorder, affecting 1% to 2% of the population, characterized by daily or near-daily headache aggravated by chronic acute medication intake. Primary headache patients do not necessarily develop MOH after acute medication overuse, although a pre-existing primary headache is inevitably present. Likewise, headache patients may deteriorate in terms of frequency without medication overuse, or suffer from chronic headache in the presence of drug abuse without any causal relationship. To classify and define diagnostic criteria for MOH in the absence of objective biomarkers is a difficult task that is presently based on clinical grounds and is limited in part by the relative lack of research in this field. The present criteria are less restrictive but also less precise than the previous versions because they allow the diagnosis without the previously required MOH confirmation after medication withdrawal. MOH should remain as a distinct secondary disorder based on the available clinical and pathophysiological evidence.     

Medication-overuse headache: Description, treatment, and relapse prevention

Medication-overuse headache (MOH) has increasingly become a focus within the field of headache. The biologic and physiopathologic origin for MOH likely resides in receptor physiology, but it also is probable that the initiation and sustaining dynamics of this pathologic condition involve several other factors. Not all patients with frequent headache eventually overuse their medications, but when it happens (the percentage is approximately 1%), the diagnosis of MOH is clinically important because patients rarely respond to preventive medications while overusing acute medications. Properly treating medication overuse and preventing relapse require recognition of the different factors that contribute to its development and perpetuation, including some behaviors and psychologic elements that are important in sustaining the overuse of medication. The problem regarding the diagnosis, the classification, and clinical aspects of MOH is reviewed in this article. The different therapeutic approaches, initial outcomes, and long-term durability of treatment also are discussed.     

Chronic daily headache: correlation between the 2004 and the 1988 International Headache Society diagnostic criteria

BACKGROUND: In a previous study, we compared the 1988 International Headache Society (IHS) criteria and the Silberstein-Lipton criteria (S-L) in a subspeciality clinic sample of 638 patients with chronic daily headache (CDH) assessed both clinically and with headache diaries. Both systems allowed for the classification of most patients with CDH. The 1988 IHS classification required multiple diagnoses and was more complex to apply. OBJECTIVES: The aim of this study was to revisit the same database, now comparing the prior classification systems with the new 2004 IHS classification. In contrast with the 1st edition, the 2nd edition includes criteria for chronic migraine (CM), new daily persistent headache (NDPH), and hemicrania continua (HC). METHODS: We reviewed the clinical records and the headache diaries of 638 patients seen between 1980 and 2001 at a headache center. All patients had primary CDH according to the S-L criteria. RESULTS: Using the S-L criteria as a reference, of the 158 patients with transformed migraine (TM) without medication overuse, just 9 (5.6%) met 2004 IHS criteria for CM. Most of the subjects were classified using combinations of migraine and CTTH diagnoses, much like the 1988 IHS classification. Similarly, using the new IHS system, just 41/399 (10.2%) subjects with TM with medication overuse were classified as probable CM with probable medication overuse. Most patients with NDPH without overuse were easily classified using the 2004 criteria (95.8%). Regarding NDPH with medication overuse, the diagnostic groups were much like results for the 1st edition. All patients with chronic tension-type headache (CTTH) and hemicrania continua (HC) according to the S-L system were easily classified using the 2004 IHS criteria. CONCLUSIONS: We conclude that the 2004 IHS criteria facilitate the classification of NDPH without medication overuse and HC. For subjects with TM according to the S-L system, the new IHS criteria are complex to use and require multiple diagnoses. Very few patients with TM in the S-L system could be classified with a single diagnosis in the 2004 IHS classification. In fact, CM was so rare that it would be virtually impossible to conduct clinical trials of this entity using the 2004 IHS criteria. Clinical trials of this entity should therefore be conducted using the S-L criteria. Finally, we propose that in the 3rd edition of the IHS classification, the diagnosis of NDPH be revised so as not to exclude migraine features.     

Obsessive-Compulsive Disorder and Migraine With Medication-Overuse Headache

Objective.— A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs.
Methods.— A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.— In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls ( P  < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups ( P  < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM.
Conclusions.— The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.     

Screening And Behavioral Management: Medication Overuse Headache – The Complex Case

The new appendix criteria for a broader concept of chronic migraine from the International Headache Society no longer require headache resolution or return to the previous headache pattern to confirm the diagnosis of medication overuse headache (MOH). MOH can be subdivided into simple (Type I) and complex (Type II). Complex cases may involve long-term use of daily opioids or combination analgesics, multisourcing, multiple psychiatric comorbidities, and/or a history of relapse. Daily use of opioids for other medical conditions, psychiatric comorbidity including borderline personality disorder, prior history of other substance dependence or abuse, and family history of substance disorders are risk factors for MOH. Relapse for analgesic overusers can be as high as 71% at 4-year follow-up. A case illustration spans 20 years from initial presentation through multiple periods of recovery and relapse to illustrate issues in the screening and management of complex MOH patients.     

Family History for Chronic Headache and Drug Overuse as a Risk Factor for Headache Chronification

Objectives.— To assess whether family history for chronic headache (CH) and drug overuse could represent a risk factor for headache chronification. Background.— Among factors investigated as risk factors for chronification of headache disorders, familial liability for CH and drug overuse has been rarely investigated. Patients and Methods.— A total of 105 consecutive patients with daily or nearly daily headache, and 102 consecutive patients with episodic headache matched by age, sex, and type of headache at onset, underwent a structured direct interview about family history for episodic headache, CH with and without medication overuse, substance abuse/dependence, and psychiatric disorders. Results.— In total, 80 out of 105 patients with CH received a diagnosis of medication overuse headache (MOH), 21 patients were classified as chronic migraine (CM), and 4 as chronic tension‐type headache (CTTH) without drug overuse. Some 38.1% of CH patients reported family history for CH vs only 13.7% of episodic headaches (P = .001). Familiality for CH with medication overuse was reported by 25.7% of cases vs 9.8% of controls (P = .0028). A familial history of substance abuse was reported by 20% of patients vs 5.9% of controls (P = .0026). In all, 28.7% of MOH patients reported family history for CH with medication overuse (P = .0014) and 21.2% for substance abuse (P = .002). Relatives of patients with MOH were more likely than control relatives to suffer from CH (OR = 4.19 [95% CI 2.05‐8.53]), drug overuse (OR = 3.7 [95% CI 1.66‐8.24]), and substance abuse (OR = 4.3 [95% CI 1.65‐11.19]). No differences regarding family history for episodic headache and for psychiatric disorders were found. No differences in family history for CH with drugs overuse and for substance abuse were found between CH patients without overuse and controls. Fifteen CH patients reported family history for alcohol abuse (P = .0003). Conclusions.— The significantly increased familial risk for CH, drug overuse, and substance abuse suggests that a genetic factor is involved in the process of headache chronification.     

Chronic migraine and medication overuse headache: clarifying the current International Headache Society classification criteria

Despite the recent advances in the understanding and classification of the chronic daily headaches, considerable controversy still exists regarding the classification of individual headaches, including chronic migraine (CM) and medication overuse headache (MOH). The original criteria, published in 2004, were difficult to apply to most patients with these disorders and were subsequently revised, resulting in broader clinical applicability. Nonetheless, they remain a topic of debate, and the revisions to the criteria have further added to the confusion. Even some prominent headache specialists are unsure which criteria to use. We aimed to explain the nature of the controversies surrounding the entities of CM and MOH. A clinical case will be used to illustrate some of the problems faced by clinicians in diagnosing patients with chronic daily headache.     

New appendix criteria open for a broader concept of chronic migraine

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.     

Medication–overuse headache: pathophysiological insights

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.     

The classification of chronic daily headache in adolescents--a comparison between the second edition of the international classification of headache disorders and alternative diagnostic criteria

OBJECTIVES: To compare the second edition of the International Classification of Headache Disorders (ICHD-2) and the Silberstein-Lipton (S-L) criteria in the classification of adolescents with chronic daily headache (CDH). METHODS: We reviewed the clinical records and the headache diaries of 170 adolescents (13 to 17 years) seen between 1998 and 2003 at a headache center. Relevant information was transferred to a standardized form that included operational criteria for the ICHD-2. CDH subtypes were classified according the criteria proposed by S-L into transformed migraine (TM) with (TM+) and without medication overuse (TM-), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). RESULTS: From the 69 patients with TM- according the S-L criteria, most (71%) could be classified as chronic migraine (CM), while a minority of patients required a combination of diagnosis, mainly migraine and CTTH (14.4%). Of the patients with TM+, just 39.6% met the criteria for probable CM (PCM) with probable medication overuse (PMO). If instead of 15 migraine days per month, we considered 15 or more days of migraine or probable migraine, 84% of the subjects with TM- and 68.7% of those with TM+ could be classified. Of the 27 subjects classified as NDPH without medication overuse according to the S-L system, the majority (51.2%) were also classified as NDPH according the ICHD-2. Interestingly, three (11.1% of the subjects with NDPH without medication overuse) were classified as CM in the ICHD-2 because these patients had an abrupt onset of 15 or more days of migraine per month. All patients with NDPH with medication overuse according to the S-L criteria required a combination of diagnoses in the ICHD-2. All subjects with CTTH received a single diagnosis in both classification systems. CONCLUSIONS: (i) Among adolescents with TM, the majority (58.1%) could be classified as CM, according to the ICHD-2. These results were driven by TM without medication overuse. (ii) If the ICHD-2 criteria for CM are revised to require 15 days of migraine or probable migraine, the proportion of patients with TM- who meet the criteria for CM increases from 71% to 84%; for TM+, the proportion with probable chronic migraine and PMO increases from 30% to 68%. (iii) About half of the patients with NDPH according to the S-L criteria have too many migraine features to meet ICHD-2 criteria for NDPH.     

Medication Overuse Headache in School‐Aged Children: More Common Than Expected?

Objective.— To investigate the prevalence of medication overuse headache (MOH) in a group of children and adolescents seen for headache in a third‐level center in Italy. Background.— Epidemiological studies indicate a prevalence of MOH in children and adolescents between 0.3 and 0.5%; no data are available for the Italian population. Methods.— We studied a group of first‐seen children and adolescents (118 patients, 43.2% male and 56.8% female, mean age: 11.9 years). A detailed history was taken, using criteria defined by Olesen et al to assess the presence of MOH. Statistical correlations between demographic and diagnostic variables were assessed. Results.— Eleven (9.3%) of our patients presented MOH; in the group with chronic daily headache, the prevalence raised to 20.8%. At follow up, after introduction of a more rationale treatment, most patients improved, but 2 of them reported a worsening of their headache. Conclusions.— We believe that a strong warning regarding medication overuse in headache therapy is essential for pediatricians and neuropsychiatrists.     

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study

BackgroundMedication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).MethodsRS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.ResultsIncreased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.ConclusionsThe current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.     

Tension-type headache with medication overuse: Pathophysiology and clinical implications

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.     

Gordian knot: medication overuse headache

Overuse of any kind of headache drugs may lead to the development of the medication overuse headache (MOH). Clinical features of MOH depend on the substance class that has been overused. Overuse of analgesics leads to a chronic tension-type like headache, the overuse of triptans to daily migraine-like headache or to the increase of migraine frequency. The delay between the drug overuse and onset of daily headache is shortest for triptans (1.7 years), longer for ergots (2.7 years) and longest for analgesics (4.8 years). Treatment includes withdrawal followed by structured acute therapy and initiation of specific prophylactic treatment for the underlying primary headache. The relapse rate after a successful withdrawal is about 30%. Predictors for relapse are tension-type headache and the overuse of analgesics in combination with codeine, caffeine or opioids.