Medication-overuse headache frequently coexists with primary CDH and can preclude effective therapy of the latter. In some cases medication overuse headache may be responsible for the development or maintenance of a CDH syndrome; in other cases, medication overuse is the result of frequent headaches. Prophylactic medications for primary CDH are more likely to provide benefit following successful medication-overuse headache management.
The prevalence of medication-overuse headache in the general population is ~1.5%. The female to male ratio is 3.5:1. In tertiary headache clinics throughout America, up to 50 to 80% of patients have medication-overuse headache. By far, migraine is the most common primary headache disorder associated with medication-overuse headache. In a meta-analysis summarizing 29 studies, 65% of 2612 patients with chronic medication overuse headache had migraine, 27% had tension-type, and 8% had mixed or other type of primary headache.
The risk for medication overuse headache development differs with individual substances. Opioids, butalbital-containing analgesics, and aspirin/acetaminophen/caffeine combinations are high risk; triptans are moderate risk; and NSAIDs are low risk. In a recent longitudinal population-based study, any use of barbiturates and opiates was associated with increased risk of transformed migraine. Critical dose of opiate exposure was around 8 days per month, and the effect was more pronounced in men. Critical dose of barbiturate exposure was around 5 days per month and the effect was more pronounced in women. Triptans and NSAIDs induced migraine progression in those with high frequency of migraine at baseline (10–14 days per month), but not overall.
Multiple mechanisms may be involved in the development of medication-overuse headache. Development of medication-overuse headache appears to be restricted to those with underlying headache disorders as it does not develop de novo in those without headaches who overuse the same medications.[85 86] Neurophysiologic studies have shown facilitation of trigeminal and somatic nociceptive systems in medication-overuse headache, mainly mediated at a supraspinal level. This suggests central sensitization (a process also involved in migraine pathophysiology) may also be involved in medication-overuse headache pathophysiology. Studies using 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) have identified reversible metabolic changes in pain processing structures and persistent orbitofrontal hypofunction in migraine patients with coexistent medication overuse headache. Chronic morphine exposure results in increased descending facilitation from the rostral ventromedial medulla and increased excitatory neurotransmission at the dorsal horn. Sometimes, substance addiction may be the base for medication overuse headache. Others appear to be treating pain and a comorbid anxiety disorder with the same medication (e.g., opiates). Out of 895 patients with medication overuse headache studied in a prospective fashion, 68% met three of five substance-dependence criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) versus 20% in those without medication-overuse headache. Fear of headache, anticipatory anxiety, obsessive drug-taking behaviors, and psychological drug dependence may also help induce and then sustain medication-overuse headache.
As discussed earlier, medication-overuse headache patients typically have a primary headache disorder that increased in frequency and led to increased analgesic consumption and then medication-overuse headache. It is not uncommon for patients to take frequent analgesics solely to prevent a severe analgesic-withdrawal headache. Medication overuse headache varies in its characteristics (severity, location, type) and is frequently associated with nausea, asthenia, and cognitive difficulties (impaired memory, poor concentration, irritability). If a CDH sufferer is taking analgesics more than 2 to 3 days per week on average, medication-overuse headache should always be suspected. The following are current ICHD-2 diagnostic criteria for medication overuse headache. Please note that the type of medication overused is important for proper diagnosis.
Headache present on ≥15 days/month
Regular overuse for >3 months of one or more acute/symptomatic treatment drugs
Ergotamine, triptans, opioids, or combination analgesic medications on ≥10 days/month on a regular basis for >3 months
Simple analgesics or any combination of ergotamine, triptans, analgesic opioids on ≥15 days/month on a regular basis for >3 months without overuse of any single class alone
Headache has developed or markedly worsened during medication overuse
Abrupt drug withdrawal remains the treatment of choice when dangerous physical withdrawal is not a concern. Proper management of medication-overuse headache should include the following steps:
Withdrawal of offending medication
"Bridging" aimed at symptomatic relief during medication withdrawal
Establish new acute and preventive headache treatment regimen
Follow-up and headache reassessment
Patients with medication-overuse headache need to understand that as long as they are overusing analgesics, headache preventives may be less effective or not effective at all.[79,89] They need to be educated on why analgesic overuse is detrimental. The majority of medication-overuse headache patients benefit from drug withdrawal. Benefit may be from the withdrawal alone or from a "reparative" change from treatment failure to favorable response to medical management.[79,92]
Withdrawal of the Offending Medication
During analgesic withdrawal, headaches frequently exacerbate before starting to improve. Nausea, vomiting, restlessness, anxiety, and sleep disturbances may also occur during withdrawal.[85,89] Withdrawal symptoms usually last 2 to 10 days (mean 3.5 days), but can endure for 2 to 4 weeks. Although many physicians prefer inpatient programs for withdrawal, most patients can be managed on an outpatient basis. A recent prospective, randomized trial in patients with migraine and superimposed medication-overuse headache showed that simple, strong advice was as effective as structured inpatient and outpatient detoxification programs in achieving medication withdrawal. The mean success rate of withdrawal treatment at 1 to 6 months was 72.4% in a meta-analysis.
The goal of "bridging" is to provide symptomatic relief during acute medication withdrawal. No clear guidelines or consensus recommendations exist. Bridging recommendations are based on case series, retrospective chart reviews, prospective uncontrolled studies, and expert opinion. Some studies support the use of corticosteroids; others do not. Further randomized, placebo-controlled trials are needed to clarify the potential role of corticosteroids in medication-overuse headache management. Antiemetics are often prescribed in addition to the following published strategies.
Naproxen 500 mg twice a day until withdrawal is complete
Naproxen sodium 550 mg twice a day for 2 to 4 weeks
Naproxen sodium 550 mg twice a day for 1 week, then once a day for 1 week
Prednisone 60 mg/day, decrease by 20 mg every 2 days (total 6 days)
Prednisone 100 mg for 5 days
IV or intramuscular (IM) dexamethasone 8 to 20 mg/day, tapering over 2 to 3 days
IV hydrocortisone 100 mg every 6 hours for 24 hours; every 8 hours for 24 hours; then every 12 hours for 24 hours
Repetitive IV dihydroergotamine (DHE; inpatient): IV metoclopramide 10 mg, followed by 0.5 mg IV DHE. Doses adjusted based on headache severity and side effects
Continuous IV DHE (inpatient): 3 mg of DHE in 1000 mL of normal saline at 42 mL/h by IV infusion pump, totaling 3 mg of DHE administered at constant rate over 24 hours
Subcutaneous DHE (outpatient): 1 mg twice a day for 1 week followed by 0.5 mg twice a day for 1 week, or 1 mg twice a day for 1 week followed by 1 mg every day for 1 week
IV valproate sodium: loading dose of 15 mg/kg followed by daily maintenance of 5 mg/kg every 8 hours for 12 to 48 hours
IV prochlorperazine starting with 5 mg to 10 mg every 8 hours, with dosage adjustment according to efficacy and side effects until headache-free
Establish Appropriate Headache Prevention
Whether pharmacologic prophylaxis should be started at the time of medication withdrawal remains an ongoing dispute. Because most patients will require long-term preventives, the authors recommend starting such treatment at the time of withdrawal. Preventives are chosen according to the type of underlying primary headache disorder.
Follow-up and Headache Reassessment
Once the overused medications have been withdrawn, patients frequently return to a pattern of intermittent headaches. These headaches need to be classified and treated accordingly.
Most relapses occur in the first year following withdrawal. In general, avoidance of opiates and/or butalbital for the regular management of primary headache disorders is recommended. Limitations for the frequency of analgesic intake should be explained: triptan or combination analgesic use should be limited to 9 or fewer days a month on average and NSAIDs to 15 or fewer days a month to prevent medication-overuse headache relapse. The identification and management of comorbidities (anxiety, etc.) that may contribute to medication overuse headache development and preservation are of paramount importance to prevent medication overuse headache relapse.
Semin Neurol. 2010;30(2):154-166. © 2010 Thieme Medical Publishers
Cite this: Diagnosis and Management of Chronic Daily Headache - Medscape - Apr 01, 2010.