Headache From Medication Overuse

Etiology

For diagnosis of medication overuse headache under the most recent ICHD-3b criteria, the following three points must be met: 

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

Medication overuse headache is thought to occur when patients are taking acute headache medication with the following frequencies: 15 days or more per month for simple analgesics (i.e., acetaminophen, NSAIDs); and ten days or more per month for ergotamine, triptans, opioids, or combination analgesics (i.e., butalbital/acetaminophen/caffeine).[6][7]

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

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 headache. For example, given the differences in efficacy in treating migraines between acetaminophen 1000 mg PO (NNT=12) and ibuprofen 400 mg by mouth (NNT= 7.2), the patient using acetaminophen will generally end up requiring more frequent dosages of this medication to control a headache compared to those who are using ibuprofen.

Epidemiology

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

It occurs fairly commonly in patients with chronic migraines (CM), with estimates of about 32% of patients within the chronic migraine group having medication overuse headaches. Medication overuse headache is believed to be more common in women (male to female ratio ranging from 2 to 1 to 5 to 1) and those with low socioeconomic status.[8]

Pathophysiology

The exact mechanism of medication overuse headache is unclear. It is hypothesized that medication overuse headache is attributed to the depletion of 5-HT by overuse of headache abortive medications. This leads to neuronal hyperexcitability in the cerebral cortex (which can lead to cortical spreading depression) and the trigeminal system (which produces peripheral and central sensitization). The decrease in 5-HT levels leads to increased CGRP release from trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.

Other studies demonstrate structural and functional brain changes that occur in medication overuse headaches. There are notable changes in metabolism in various brain structures as seen on PET scans of medication overuse headache patients. These changes were mostly reversed upon withdrawal of analgesic medication, except for persistent hypometabolism seen in the orbitofrontal area. This particular 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 headache.[9]

History and Physical

Clinical presentation of medication overuse headache varies between patients and even changes with time in the same patient. There can be an increase in the frequency of a pre-existing headache or the evolution into a new type of headache. There are no specific tests to diagnose this condition, and thus it is headache quantity and frequency, and type and frequency of acute medication used that leads to the diagnosis.[10] Although pain location and quality are non-specific in medication overuse headache, there are some general features commonly seen in this patient population; these include the following:

• The headaches are usually episodic
• Frequent acute medication consumption depends on the type of abortive medication used (see Etiology section for more detail)
• Neck pain is common (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
• Autonomic symptoms (i.e., nasal congestion, rhinorrhea, gastrointestinal [GI] disturbance) are more frequent with overused opioids
• Comorbid anxiety and depression
• All headache treatments are generally less effective when medication overuse headache is present; efficacy improves after the weaning.

Evaluation

There are currently no specific biomarkers or studies whereby differentiate or point towards medication overuse headache. The diagnosis is purely clinical and deserves special attention, not to be overlooked due to the potential consequences of worsening over time.

Treatment / Management

Typical treatment involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete 100% weaning of overused acute medication shows the best results compared to continuing on the same acute medication responsible for medication overuse headache but placing frequency limits on its use. Note that patients can be prescribed a new acute medication from a different class. Patients can wean from the offending medication abruptly ("cold turkey") or gradually over several weeks. Preventative treatment can include prophylactic medication and/or non-pharmaceutical treatments (i.e., cognitive behavioral therapy, biofeedback, relaxation training, lifestyle modification with trigger avoidance).[11][12][13]

Educating the patient and their family on 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 thought to typically last up to 10 days, then eventually followed by improvement in medication overuse headache. 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. It is important to address and treat co-morbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, but without potentiating the boosting effects, anxiolytic medication has in maintaining the headache.

Following successful weaning, about half of patients relapse after five 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 professionals suggest tapering prophylactic medication after one year.[14][15]

Differential Diagnosis

Medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. Other secondary headaches must be ruled out with the guidance of the patient's clinical picture and the aid of all the necessary tests, more so when the features of the original episodic headache are different from its chronic counterpart.[16][17]

Prognosis

The results of a tailored regime are excellent in the long-term, but with an estimated relapse rate of about 30% within six months and 50% following a 5-year period.[18]

Complications

Complications that may accompany medication overuse headaches are symptomatic. These include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[19]