Abstract
Worldwide, chronic daily headache (CDH) has become a significant public health concern because of its high prevalence (3–4%) and considerable disability. It is a group of disorders in which headache occurs ≥ 15 days/month for at least 3 months and includes the following diagnostic subtypes: chronic migraine, chronic tension-type headache, hemicrania continua and new daily persistent headache. Of note, many patients with CDH also overuse acute medications. Medication overuse headache (MOH) was first classified by Silberstein and Lipton (S-L criteria) and then affirmed by the International Classification of Headache Disorders, 2nd edn (ICHD-2), 2004 with further modifications in 2006. It has been estimated that around one-third of patients with CDH have MOH. In this paper, we present the profile of MOH in Taiwan.
EPIDEMIOLOGICAL SURVEYS
We have performed three large-scale population-based surveys of CDH as well as MOH in different age groups in Taiwan (Table 1). In 1997, we surveyed 3377 subjects aged ≥ 15 years in Taipei and found that 108 (3.4%) of them had CDH (1). Of these, 37 (34% of CDH subjects; 1.1% of all studied subjects) met the S-L criteria for medication overuse. Medications overused included both simple analgesics (46%) and compound analgesics (54%). None of the CDH subjects in the survey overused narcotics or ergotamine. We found that over-the-counter medications were the single most common source for these analgesics (73%), followed by prescription drugs (22%) and, in some cases, both (5%). Compared with non-over-users, medication over-users were older (45 ± 15 vs. 36 ± 14 years, P < 0.005), but neither group differed in sex distribution or subtypes of CDH. When analysing the reasons for using acute medications, we found that the majority (87%) of the CDH subjects without medication overuse reported that they did not use any painkillers until the headache became ‘truly big or annoying’. In contrast, 46% of subjects with medication overuse admitted that they took painkillers even when their headaches were trivial, because ‘I have to stop the headache before it gets bigger’ (n = 8). For some patients it was: ‘I can not tolerate any functional limitation at all’ (n = 5), or ‘I can not tolerate any pain at all’ (n = 3). Clearly, anticipation and avoidance of severe disability due to acute attacks are important factors contributing to medication overuse. As with other population studies of this problem worldwide, this study demonstrated that the prevalence of MOH was around 1%. At the 2-year follow-up (with 37 subjects with MOH identified at the initial survey), 36 patients were still available for follow-up. Of these, 16 (44%) continued with MOH, two (6%) had stopped overuse but were still bothered by CDH, and the remaining 18 (50%) were free from CDH and no longer overused analgesics.
Three population-based surveys of CDH and MOH in Taiwan
CDH, chronic daily headache; MOH, medication overuse headache.
In a survey of the elderly (age ≥ 65 years old; n = 1533, mean age 73.7 ± 6.9 years) done in Kinmen, Taiwan in 1993, we found 60 subjects (3.9%) had CDH (2). Of these, 15 (25% of CDH subjects, 1% of all subjects) had MOH. The most commonly overused medications in this study were combinations of paracetamol/aspirin and caffeine (47%), followed by aspirin (20%) and paracetamol (20%). To our surprise, we found no decline in the prevalence of CDH or MOH in the elderly subjects similar to that of migraine headaches. In fact, the results in this elderly sample are quite similar to those done in the general population. Of note, MOH was quite protracted in this age group, and 11 of 15 patients (73%) with MOH still had MOH at 2-year follow-up.
In 2000, we conducted a headache survey of 7900 adolescent students (aged 12–14 years) in five middle schools in Taiwan (3). The 1-year prevalence of CDH was estimated as 1.5% (n = 122), and 0.3% (n = 24) of adolescents could be diagnosed as MOH, accounting for one-fifth of all CDH sufferers. All of them overused over-the-counter painkillers. Eighteen (75%) overused combination analgesics containing caffeine and six respondents used simple analgesics (paracetamol in all). None of our CDH subjects overused ergotamine, triptans or narcotics. In contrast to previous studies, we found medication overuse was an important underlying mechanism for adolescent CDH. Criteria bias might have contributed to this discrepancy. The previously used S-L criteria are more strict in defining MOH, because both the frequency and the total amount of symptomatic medications were counted, whereas the ICHD-2 criteria consider only the frequency. In fact, only six subjects fulfilled the S-L criteria for MOH (5% of all CDH subjects) in this study. Therefore, the new ICHD-2 criteria increased, by fourfold, the prevalence of MOH; however, the validity still needs to be examined. Of note, adolescents with MOH had a higher rate of remission and only 22% of them had MOH at 2-year follow-up.
CLINIC-BASED STUDIES
A recent clinical study done at the Headache Clinic, Taipei Veterans General Hospital, recruited 2983 new patients aged > 18 years, of whom 1861 (mean age 49.6 ± 15.4 years, 62.4% of total sample) had CDH. Of the 1861 patients recruited, 895 (48%) had MOH based on the ICHD-2 (4). Compared with those patients without MOH, MOH patients were more likely to be female [odds ratio (OR) 1.32], have less education and to have experienced migraine headache, have longer duration of CDH, more severe intensity headaches, more frequent attacks and higher rates of physician consultation. Patients with MOH also demonstrated higher psychological distress as measured by the Hospital Anxiety and Depression Scale. Of note, according to Diagnostic and Statistical Manual of Mental Disorders, 4th edn substance dependence criteria, 606 of the 893 patients with MOH (68%) were classified as having substance dependence, whereas only 191 of 968 CDH patients without MOH (20%) were so classified (OR 8.6, P < 0.001). These study results showed that MOH might, at least in some patients, represent a type of dependence behaviour. This finding has several implications. First, incorporation of the concept of dependence into the treatment of MOH might help clinicians handle this important disorder in a more proper and comprehensive therapeutic programme. Second, acknowledging MOH as a ‘dependence’ behaviour similar to that seen with other compulsive behaviours may help patients and clinicians understand the recurrent nature of repeated drug overuse.
OVERUSED MEDICATIONS
As we have seen with the community-based studies, most headache clinic patients with MOH overused simple analgesics (with/without caffeine). In Taiwan, overuse of narcotics or combinations of simple analgesics, opioids and butabital in patients with MOH is very rare because of the severe restriction of the former in medical use by physicians and unavailability of the latter. It is estimated that, in our headache clinic, around 7.5% of patients with MOH due to ergotamine and caffeine but overuse of triptan is very rare. Overuse of anti-cold liquid medications is not uncommon in Taiwan and accounts 24% of patients with MOH in our headache clinic. There are > 100 brands of anti-cold liquids available in Taiwan. Most of them are bottled in 60-ml quantities. Paracetamol (7.5–15 mg/cm3), caffeine, chlorpheniramine, methylephedrine and guaifenesin comprise the main components of these cold treatments. Of these, paracetamol and caffeine are commonly used for pain relief, especially for headache. Again, anti-cold liquids are sold as over-the-counter medicines in pharmacies. Although these cold liquids have a suggested dosage of 10 ml per treatment, patients with MOH have frequently reported taking an entire bottle per treatment dose. Patients with anti-cold liquid MOH are commonly less educated and have longer duration of CDH in comparison with those who overused other acute medications (unpublished data). Most of the cold liquid medication abusers (88%) also took other acute medications.
TREATMENT
In Taiwan, we do not have dihydroergotamine injections. Therefore, intravenous prochloroperazine has been commonly used instead for withdrawal headache during detoxification in hospital. In a previous study, a total of 135 patients with refractory CDH were recruited, including 95 (70%) with analgesic overuse (5). After intravenous prochlorperazine treatment, 121 (90%) achieved at least a 50% reduction in headache intensity, including 85 (63%) who became headache free. The mean hospital stay was 6.2 ± 2.7 days, and mean total prochlorperazine used was 98 ± 48 mg. Acute extrapyramidal symptoms occurred in 21 (16%) patients. In total, 124 (92%) patients were successfully followed up, with a mean duration of 14.3 ± 7.5 months. When asked to compare their current headache status with that prior to treatment, 93 patients (75%) reported decreased headache intensity and 86 (69%) reported a decrease in their headache frequency, even though 40 (32%) still had a daily headache at follow-up. Of the 87 patients with analgesic overuse who could be followed, 61 (70%) no longer overused analgesics. We consider that prochlorperazine is effective and safe in the treatment of patients with MOH. Compared with dihydroergotamine, prochlorperazine seems less effective in achieving ‘freedom from headache’ during hospitalization, but has a similar outcome at follow-up. In Taiwan, like other countries, prophylactic agents including propranolol, flunarizine, amitriptyline, valproic acid or topiramate are always given to MOH patients after detoxification for a period of at least several months and are tapered if their headache symptoms improve substantially.
PROGNOSIS
In our three prospective epidemiological studies of CDH in different age groups (1–3), we consistently found that the presence of medication overuse is predictive of persistent CDH, i.e. a poor outcome predictor. In addition, we also found elderly patients with MOH had the highest persistence rate of MOH at the 2-year follow-up. Therefore, withdrawal of the overused medications is of utmost importance in the successful treatment of patients with MOH.
CONCLUSIONS
The prevalence of MOH in Taiwan is similar to that in other parts of the world. It affects 1% of the general population. Simple analgesics, with and without caffeine, and obtained as over-the-counter treatments are the two most overused medications. In addition, overuse of anti-cold liquids is still common, particularly in those patients with less education. Our studies have also shown that MOH represents a type of dependence behaviour in at least some patients. Also, in Taiwan in-patient intravenous prochloperazine is used for withdrawal headache during detoxification. Medication overuse predicted poor outcome in patients with CDH. Older patients with MOH had a higher persistence rate of MOH than younger patients. The prognosis is generally satisfactory if overused medications can be withdrawn.