Medication Overuse Headache

Etiology

To diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled:

• A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder.
• A patient must have misused the acute headache medication for 3 or more months.
• A headache is not attributable to another ICHD-3 headache condition.

Medication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.[7][8]

The ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately.

The most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches.

Patients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.[9]

Epidemiology

Medication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases.

Medication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.[10]

Pathophysiology

The exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.[11]

Other studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.[12] PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.[13][14][13]

History and Physical

Clinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.[15]

Although pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including:

• The headaches are typically episodic.
• Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.[16]
• Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments.
• Typically occurs in the morning, presumed related to withdrawal occurring during sleep.
• Poor sleep quality.
• Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids.
• Comorbid anxiety and depression.
• All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal.

Evaluation

There are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time.

Treatment / Management

Education is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.[17](A1)

In addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.[18][19][20]

Educating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.[14] Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches.

Following successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.[21][22]

Differential Diagnosis

A medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.[23][24]

Prognosis

A tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.[25]

Complications

Complications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[26]