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.     

Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took >10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications.     

Team players against headache: multidisciplinary treatment of primary headaches and medication overuse headache

Multidisciplinary approaches are gaining acceptance in headache treatment. However, there is a lack of scientific data about the efficacy of various strategies and their combinations offered by physiotherapists, physicians, psychologists and headache nurses. Therefore, an international platform for more intense collaboration between these professions and between headache centers is needed. Our aims were to establish closer collaboration and an interchange of knowledge between headache care providers and different disciplines. A scientific session focusing on multidisciplinary headache management was organised at The European Headache and Migraine Trust International Congress (EHMTIC) 2010 in Nice. A summary of the contributions and the discussion is presented. It was concluded that effective multidisciplinary headache treatment can reduce headache frequency and burden of disease, as well as the risk for medication overuse headache. The significant value of physiotherapy, education in headache schools, and implementation of strategies of cognitive behavioural therapy was highlighted and the way paved for future studies and international collaboration.     

Treatment-resistant medication overuse headache can be cured

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

Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness

It is generally accepted that ongoing medication overuse nullifies the effect of prophylactic treatment, although few data support this contention. We set out to describe the treatment outcome in patients withdrawn from medication overuse and relate any improvement to a renewed effect of prophylaxis. For patients with probable medication-overuse headache (pMOH), treated and dismissed from the Danish Headache Centre in 2002 and 2003, we assed, from prospective headache diaries, the headache frequency before and after withdrawal of offending drugs and compared these frequencies with the headache frequency at dismissal. Among 1326 patients, 337 had pMOH. Eligible were 175, mean age 49 years, male/female ratio 1 : 2.7. Overall, there was a 46% decrease in headache frequency from the first visit to dismissal (P < 0.0001). Patients with no improvement 2 months after complete drug withdrawal (N = 88) subsequently responded to pharmacological and/or non-pharmacological prophylaxis with a 26% decrease in headache frequency as measured from the end of withdrawal to dismissal (P < 0.0001). At dismissal, 47% were on prophylaxis. Former non-responders to medical prophylaxis had a 49% decrease in headache frequency from first visit to dismissal (P < 0.0001), whereas those who had never received prophylaxis had a 56% reduction (P < 0.0001). This difference was not statistically significant (P = 0.22). Almost all MOH patients benefit from drug withdrawal, either just from the withdrawal or by transformation from therapeutic non-responsiveness to responsiveness. According to the International Classification of Headache Disorders, 2nd edn, the MOH diagnosis requires improvement after drug withdrawal. Our data suggest that these diagnostic criteria are too strict.     

Prevalence, pattern and predictors of use of complementary and alternative medicine (CAM) in migraine patients attending a headache clinic in Italy

The use of complementary and alternative medicine (CAM) in migraine is a growing phenomenon about which little is known. This study was undertaken to evaluate the rates, pattern and presence of predictors of CAM use in a clinical population of patients with different migraine subtypes. Four hundred and eighty-one migraineurs attending a headache clinic were asked to undergo a physician-administered structured interview designed to gather information on CAM use. Past use of CAM therapies was reported by 31.4% of the patients surveyed, with 17.1% having used CAM in the previous year. CAM therapies were perceived as beneficial by 39.5% of the patients who had used them. A significantly higher proportion of transformed migraine patients reported CAM treatments as ineffective compared with patients suffering from episodic migraine (73.1% vs. 50.7%, P < 0.001). The most common source of a recommendation of CAM was a friend or relative (52.7%). In most cases, migraineurs' recourse to CAM treatments was specifically for their headache (89.3%). Approximately 61% of CAM users had not informed their medical doctors of their CAM use. The most common reason for deciding to try a CAM therapy was that it offered a 'potential improvement of headache' (47.7%). The greatest users of CAM treatments were: patients with a diagnosis of transformed migraine; those who had consulted a high number of specialists and reported a higher lifetime number of conventional medical visits; those with a comorbid psychiatric disorder; those with a high income; and those whose headache had been either misdiagnosed or not diagnosed at all. Our findings suggest that headache clinic migraine patients, in their need of and quest for care, seek and explore both conventional and CAM approaches. Physicians should be made aware of this patient-driven change in the medical climate in order to prevent misuse of healthcare resources and to be better equipped to meet patients' needs.     

Acupuncture use for the treatment of headache prior to neurological referral

Acupuncture is a popular complementary treatment for various pain syndromes. Some studies claim efficacy in the treatment of primary headache syndromes. However, data on the frequency of acupuncture use by patients with headache prior to neurological referral have not been identified. In this study, 12% of patients with headache attending general neurology outpatient clinics had already received acupuncture; of the remainder, 73% said they would be willing to try it.     

Encopresis in a multihandicapped child: Rapid multidisciplinary treatment

An 8-year-old child with cognitive, behavioral, and speech and language impairments presented to a multidisciplinary diagnostic and treatment center with long-standing secondary encopresis. The medical and behavioral literature is reviewed. The case is used to illustrate how: (1) secondary encopresis is often unreported because parents and some health professionals assume it is a natural part of the syndrome of disabilities of a multiply handicapped child; (2) it can present as a social emergency when community agencies are inconvenienced by this symptom; (3) a multidisciplinary team, using community resources, can successfully treat this symptom in the face of a number of factors which generally point toward a poor prognosis for rapid elimination of this symptom. Health professionals are urged to routinely inquire about secondary encopresis to insure that this symptom is not ignored.     

Prevalence of headache in Europe: a review for the Eurolight project

The main aim of the present study was to do an update on studies on headache epidemiology as a preparation for the multinational European study on the prevalence and burden of headache and investigate the impact of different methodological issues on the results. The study was based on a previous study, and a systematic literature search was performed to identify the newest studies. More than 50% of adults indicate that they suffer from headache in general during the last year or less, but when asked specifically about tension-type headache, the prevalence was 60%. Migraine occurs in 15%, chronic headache in about 4% and possible medication overuse headache in 1–2%. Cluster headache has a lifetime prevalence of 0.2–0.3%. Most headaches are more prevalent in women, and somewhat less prevalent in children and youth. Some studies indicate that the headache prevalence is increasing during the last decades in Europe. As to methodological issues, lifetime prevalences are in general higher than 1-year prevalences, but the exact time frame of headache (1 year, 6 or 3 months, or no time frame stated) seems to be of less importance. Studies using personal interviews seem to give somewhat higher prevalences than those using questionnaires.     

Outcomes of a headache-specific cross-sectional multidisciplinary treatment program

Aim.— Chronic headache is a disabling disorder that is frequently poorly managed in general clinical practice. Objectives.— To investigate primary (headache frequency in days/month) and secondary (headache‐related disability, lost work/school time, anxiety and depression, amount and intake frequency of acute medication) 12‐month outcomes of a headache‐specific cross‐sectional outpatient and inpatient multidisciplinary treatment program using a dedicated computer system for data collection and corresponding between integrated care team in a tertiary headache center and practicing headache specialists. Background.— A need for integrated headache care using comprehensive and standardized assessment for diagnosis of headache, psychiatric comorbidity, and burden of disease exists. There are little published data on long‐term efficacy of multidisciplinary treatment programs for chronic headache. Design.— A prospective, observational, 12‐month, follow‐up study. Subjects and Methods.— Prospectively recruited consecutive patients with frequent difficult‐to‐treat headaches (n = 201; 63 migraine, 11 tension‐type headache, 59 combined migraine/tension‐type headache, and 68 medication overuse headache) were enrolled. Outcome measures included prospective headache diaries, a medication survey, Migraine Disability Assessment, 12‐item short form health survey, and the Hospital Anxiety and Depression Scale. Results.— The primary outcome of a reduction of ≥50% of headache frequency (days/month) was observed in 62.7%. Mean headache frequency decreased from 14.4 ± 8.2 to 7.6 ± 8.3 days/month, P < .0001. Secondary outcomes improved significantly in the total cohort and all headache subgroups. Predictors for good outcome were younger age, few days lost at work/school, and familiarity with progressive muscle relaxation therapy at baseline. Conclusions.— The present analysis provided support for a cross‐sectional multidisciplinary integrated headache‐care program.     

Placebo and other psychological interactions in headache treatment

We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients’ expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of administration was limited, the control of attacks uncertain as well as the evolution of the co-morbid psycho-pathology. Considering the reviews and meta-analysis of complex prophylactic procedures, it must be concluded that their effect is mostly linked to a placebo and non-specific psychological effects. Acupuncture may have a slight specific effect on tension type headache, but not on migraine. Manual therapy studies do not exhibit difference between manipulation, mobilization, and controls; touch has no proven specific effect. A comprehensive efficacy review of biofeedback studies concludes to a small specific effect on tension type headache but not on migraine. A review of behavioral treatment conclude to an interesting mean improvement but did not demonstrated a specific effect with the exception of a four arm study including a pseudo meditation control group. Expectation-linked placebo, conditioning, and non-specific psychological effects vary according clinical situations and psychological context; likely low in RCT, high after anempathic medical contact, and at its maximum with a desired charismatic healer. The announcements of doctors strongly influence the beliefs of patients, and in consequence their pain and anxiety sensibilities; this modulates the amplitude of the placebo and the non-specific psychological effects and is therefore a major determinant of the therapeutic success. Furthermore, any repetitive contact, even through a placebo, may interfere positively with the psychopathological co-morbidity. One has to keep in mind that the non-specific psychological interactions play a major role in the improvement of the majority of the headache sufferers.     

Disability in chronic migraine with medication overuse: treatment effects at 3 years

OBJECTIVES: To determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated 3 years previously. BACKGROUND: Patients who have chronic migraine accompanied by medication overuse are particularly difficult to treat. Investigations are limited in number, few have included follow-up beyond 6 months, and almost none have examined whether treatment leads to concurrent improvements in disability and functional impairment. In a prior report, we described the clinical course of 84 such patients followed for 1 full year after treatment. METHODS: These same 84 patients were followed for 2 additional years to assess longer term maintenance of effects, using measurement procedures identical to those in the original investigation. RESULTS: Both endpoint and completer analyses revealed significant improvement on all measures studied-headache days per month, analgesic consumption, and MIDAS scores (Total, Headache Frequency, and Headache Intensity)-with some loss of benefits over time for the pain indices. MIDAS total scores, however, were lower at 36 months than at 6 months. Comparisons of those who completed the 3-year follow-up to those who did not revealed few differences at baseline. All of this suggests attrition did not have a bearing on outcome. DISCUSSION: High levels of maintenance were revealed at 3 years. Even though reports of pain revealed some lessening of effects, this was not accompanied by reports of deterioration in functioning. This suggests that patients have learned to adapt and adjust to headaches in their daily lives.     

The burden of headache in a patient population from a specialized headache centre

The aim was to characterize the individual and socio-economic impact of headache in a patient population from The Danish Headache Centre. This was a cross-sectional study using a structured interview, prospective headache diaries and standardized self-administered questionnaires using the ICHD-II criteria. Fifty-five subjects (12 male and 43 female) with a median age of 41 years and a median headache frequency of 15 days/month participated. Very high utilization of the healthcare system and a high absence rate due to headache of 12 days/year were reported. Eighty-one percent experienced a marked decrease in work effectiveness. Overall, 91% felt hampered by their headache on a daily basis and 98% had had expenses for headache medication. Frequent headache disorders are highly costly, especially due to indirect costs. Prevention, early intervention or effective treatment strategies for headache disorders may therefore be highly cost effective, not only for the individual but also for society.     

Butalbital in the treatment of headache: history, pharmacology, and efficacy

Analgesics containing butalbital compounded with aspirin, acetaminophen, and/or caffeine are widely used for the treatment of migraine and tension-type headache. The butalbital-containing compounds are efficacious in placebo-controlled trials among patients with episodic tension-type headaches. Despite their frequent clinical use for migraine, they have not been studied in placebo-controlled trials among patients with migraine. Barbiturates can produce intoxication, hangover, tolerance, dependence, and toxicity. Butalbital can result in intoxication that is clinically indistinguishable from that produced by alcohol. Butalbital-containing analgesics can produce drug-induced headache in addition to tolerance and dependence. Higher doses can produce withdrawal syndromes after discontinuation. Butalbital-containing analgesics may be effective as backup medications or when other medications are ineffective or cannot be used. Because of concerns about overuse, medication-overuse headache, and withdrawal, their use should be limited and carefully monitored.     

Anti-epileptic drugs in the preventive treatment of migraine headache: a brief review

Anti-epileptic drugs are employed for the prophylactic treatment of migraine. Valproic acid and its sodium salt (divalproex) have been shown to be effective in preventing migraine in double-blind placebo-controlled studies. Gabapentin and lamotrigine have also been proposed for migraine prophylaxis, but more extensive studies are needed to confirm their efficacies. The main mechanism of action of anti-epileptic drugs in the inhibition of the sodium channel to induce a depolarization, preventing the high, frequent action potentials typically excited by convulsive attacks. Moreover, valproate and gabapentin increase brain concentrations of GABA and, probably, inhibit the degradation of GABA. Other proposed mechanisms of action for valproate are a direct effect on neuronal membranes and a reduction of excitatory transmission by aspartate. Valproate, at the recommended dose of 500 mg twice daily, is well tolerated. The more frequent unwanted effects associated with almost all drugs of this class are weight gain, drowsiness, dizziness and tremor. Topiramate has recently been proposed for the treatment of unresponsive, high frequency migraine, taking into account both the GABA and glutamatergic mechanisms of action. Received: 13 November 2000 / Accepted in revised form: 5 April 2001     

Basal cutaneous pain threshold in headache patients

The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ ² 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ ² 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization.     

Incidence and influence on referral of primary stabbing headache in an outpatient headache clinic

Primary stabbing headache (PSH) is a pain, as brief, sharp, jabbing stabs, predominantly felt in the first division of trigeminal nerve. Population studies have shown that PSH is a common headache. However, most people suffer attacks of low frequency or intensity and seldom seek for medical assistance. There are few clinic-based studies of PSH, and its real influence as a primary cause for referral to neurology outpatient offices is to be determined. We aim to investigate the burden of PSH as main complaint in an outpatient headache clinic. We reviewed all patients with PSH (ICHD-II criteria), attended in an outpatient headache clinic in a tertiary hospital during a 2.5-year period (January 2008–June 2010). We considered demographic and nosological characteristics and if PSH was main cause of submission. 36 patients (26 females, 10 males) out of 725 (5%) were diagnosed of PSH. Mean age at onset 34.1 ± 2.9 years (range 10–72). Mean time from onset to diagnosis 68.8 ± 18.3 months. Twenty-four patients fulfilled ICHD-II criteria for other headaches (14 migraine, 6 tension-type headache, 2 hemicrania continua, 1 primary cough headache and 1 primary exertional headache). 77.7% of patients were submitted from primary care. In 14 patients (39%), PSH was main reason for submission, its intensity or frequency in 5 (35.7%) and fear of malignancy in 9 (74.3%). Only two patients of those who associated other headaches were submitted due to PSH. In conclusion, PSH is not an uncommon diagnosis in an outpatient headache office. However, and according to our data, it is not usually the main cause of submission to a headache clinic.