Medication-Overuse Headache in Japan

STATISTICS AND CLINICAL CHARACTERISTICS The phenomenon of medication overuse headache (MOH) was first described in 1951. The case was overuse of ergotamine. Patients who took ergotamine on a daily basis developed daily headache and improved significantly after withdrawal of ergotamine. Many terms, such as drug-induced headache and medication misuse headache, have been used to describe this entity. The term medication overuse headache was introduced into the International Headache Society’s classification in 2004 (ICHD-II), and a further modification has been made. The new classification defines subforms of MOH according to causal drugs. Epidemiological studies indicate that the prevalence of chronic headache is about 4–5%, and the prevalence of chronic headache due to overuse of analgesics is about 1%. MOH is a growing worldwide problem in clinical practice. Japan is not an exceptional area, even though specific statistics are scarce. Since studies from other Asian countries have indicated no racial differences in MOH prevalence, Japan seems to have a similar prevalence of MOH. However, the drugs which cause MOH may vary from country to country, since their availabilities in the market differ, and cultural factors greatly affect people’s attitudes. Combination analgesics, which are the major candidates for MOH in the USA and Europe, may contain codeine, barbiturates or caffeine. Neither codeine nor barbiturate is used in combination analgesics in Japan. The introduction of the first triptan to Japan was in 2000, which was much later than in other countries. These differences in circumstances probably affect the profile of the causative drugs of MOH in Japan. Imai and colleagues have conducted a study to clarify clinical features of MOH in Japan (1). Patients with probable MOH (n = 47) according to ICHD-II were enrolled. They were 41 women and six men, mean age 42.0 years. Of the 47 patients, 38 (80.9%) had migraine only as their primary headache, and two (4.3%) had tension-type headache (TTH) only. Seven patients (14.9%) had both migraine and TTH. The overused medication was combination analgesics in 40 patients (85.1%), analgesics in four (8.5%), ergotamine in one (2.1%), triptans in one, and a combination of acute medications in one patient. The methods of withdrawal used were as follows: abrupt out-patient withdrawal, abrupt in-patient withdrawal, or tapering out-patient withdrawal. Amitriptyline was prescribed daily for management of rebound headache. Fluid replacement, antiemetics and tranquilizers were used to treat withdrawal symptoms. For prophylaxis of migraine, a calcium channel blocker, lomerizine, available only in Japan, was used (2). Triptans were used for migraine attacks. They defined complete resolution of chronic headache and analgesic use on < 10 days/month within 2 months after discontinuation of overused medications as successful withdrawal. According to this definition, 36 patients (76.6%) were successful. Nagaseki, one of the authors of this communication, and colleagues have reported a large number of MOH patients who had visited his headache clinic. There were 276 MOH patients included (40 men and 236 women, mean age 42.8 years). The age distribution of the MOH patients is shown in Fig. 1. In that study, 201 patients (72.8%) had migraine as the primary headache, including menstrual migraine. Seventy-five patients (27.2%) had other types of headache such as TTH, and headache attributed to somatization disorder (18 patients, 6.5%). One hundred and ninety-nine patients took over-the-counter (OTC) medications, which were mostly combination analgesics containing caffeine. In 184 patients (66.8%) of these, OTC medications were causative drugs for MOH. Thirteen patients (4.7%) overused triptans. The duration of suffering with MOH was from 3 months to 32 years (average 6.5 years). At the end of 3 months after withdrawal treatment started, 78% of patients improved remarkably. They stopped taking medications completely, and their headache improved. Comorbidity with depression was observed in 24.6% of the MOH patients, whereas only 12.9% of migraine patients at their clinic had depression. Nagaseki and colleagues have pointed out that MOH patients have a higher percentage of comorbidity with depression than migraine patients. Some of the MOH patients were prescribed selective 5-HT reuptake inhibitors (SSRI) during withdrawal treatment. The researchers have found use of SSRI to be effective. Diener and Dahlöf have summarized 29 studies, which included 2612 MOH patients (3). According to their metaanalysis, migraine was the primary headache in 65% of patients, TTH in 27%, and mixed or other headaches in 8%. Migraine was the primary headache in 80.9% of the MOH patients in Imai’s study, and in 72.8% of the MOH patients in Nagaseki’s. These figures were higher than the data in the meta-analysis. The prevalence of migraine in Japan is reported to be 8.4%, which is roughly equivalent to other countries (4). Thus, the higher percentage of migraine as the primary headache in Japanese MOH patients cannot be explained by a higher prevalence of migraine in Japan. Many of migraine patients in Japan do not visit a doctor and take only OTC medications. Of migraine sufferers, 56.8% use only OTC analgesics in Japan (4). Many OTC analgesics are combination medications and readily available. It can be speculated that migraine is not well controlled by OTC medications, and therefore many migraine sufferers keep taking medications, ending up with medication overuse. Some may acquire MOH in that process. It is strongly recommended Headache Currents