# Medication overuse headache

A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, can be very painful and are a common cause of chronic daily headache. They typically occur in patients with an underlying headache disorder such as migraine or tension-type headache that "transforms" over time from an episodic condition to chronic daily headache due to excessive intake of acute headache relief medications. MOH is a serious, disabling and well-characterized disorder, which represents a worldwide problem and is now considered the third-most prevalent type of headache. The proportion of patients in the population with Chronic Daily Headache (CDH) who overuse acute medications ranges from 18% to 33%. The prevalence of medication overuse headache (MOH) varies depending on the population studied and diagnostic criteria used. However, it is estimated that MOH affects approximately 1-2% of the general population, but its relative frequency is much higher in secondary and tertiary care.

## Classification

Medication overuse headache is a recognized ICHD (International Classification of Headache Disorders) classification. Over the years different sets of diagnostic criteria have been proposed and revised by the major experts of headache disorders. The term MOH first appeared in the ICHD 2nd edition in 2004. It was defined as a secondary headache, with the aim of emphasising excessive drug intake as the basis of this form of headache. The two subsequent revisions of the diagnostic criteria for MOH (2005 and 2006) refined and extended the definition of the condition on the basis of both its chronicity (headache on more than 15 days/month for more than three months) and drug classes, thereby identifying the main types of MOH. In the case of ergotamine, triptans, opioids and combination medications in particular, intake on > 10 days/month for > 3 months is required, whereas simple analgesics are considered overused when they are taken on > 15 days/month for >3 months.

## Causes

MOH is known to occur with frequent use of many different medications, including most commonly: triptans, ergotamines, simple and combination analgesics, and opioids. Common over-the-counter medicines that can cause headaches when overused include Excedrin Migraine, Cafergot, and Advil. Dietary and medicinal caffeine consumption appears to be a modest risk factor for chronic daily headache onset, regardless of headache type.
A lifelong history of headaches is a major risk factor for MOH. MOH is very rare in patients without a history of recurrent headaches, and it rarely develops in patients who take analgesics for non-headache pain, like arthritis or irritable bowel syndrome. Furthermore, MOH is more probable when a family history of MOH is present, thus indicating a genetic susceptibility. It is thought that rebound headaches are caused by a neuronal re-adjustment process. Analgesic intake raises the pain threshold. Thus, lacking pain stimuli for longer times, the brain re-calibrates to experience normal stimuli as pain.
The time it takes for someone to develop medication overuse headaches (MOH) after taking medication too often depends on the type of medication they are using. If someone is taking triptans (such as Sumatriptan etc.), it may take about 1.7 years for them to develop MOH. If they are taking ergots (such as Ergotamine etc.), it may take about 2.7 years, and if they are taking analgesics (such as Naproxen etc.), it may take about 4.8 years. So, the delay between taking medication too often and developing MOH varies based on the type of medication being used.
The underlying mechanisms that lead to the development of the condition are still widely unknown and clarification of their role is hampered by a lack of experimental research or suitable animal models. Various pathophysiological abnormalities have been reported and they seem to have an important role in initiating and maintaining chronic headache (genetic disposition, receptor and enzyme physiology and regulation, psychological and behavioural factors, physical dependencies, recent functional imaging results).
In some cases, individuals may be genetically predisposed to developing medication overuse headache. A PET study in patients with chronic analgesic overuse showed decreased activity in the orbitofrontal cortex of the brain, which is also seen in substance abuse. This suggests that there may be an underlying neurological susceptibility to addiction in some individuals. However, more research is needed to fully understand the complex interplay of factors that contribute to the development of MOH.

### Headache treatment

Opioids and butalbital are sometimes inappropriately used as treatment for migraine and headache and should be avoided in favor of more effective, migraine-specific treatments. Opioid and butalbital use can worsen headaches and cause MOH. When a patient fails to respond to other treatment or migraine specific treatment is unavailable, then opioids may be used.
Regular use of over-the-counter drugs (OTC) such as paracetamol and NSAIDs can also be a cause of MOH. OTC medication for headache should be limited to use for not more than two days weekly, and it is recommended to seek medical counsel when any pain lasts more than a few days. Concurrent with MOH, overuse of acetaminophen (known as paracetamol in some countries) for treating headaches risks causing liver damage and NSAID overuse can cause gastrointestinal bleeding.

## Prevention

In general, any patient who has frequent headaches or migraine attacks should be considered as a potential candidate for preventive medications instead of being encouraged to take more and more painkillers or other rebound-causing medications. Preventive medications are taken on a daily basis. Some patients may require preventive medications for many years; others may require them for only a relatively short period of time such as six months. Effective preventive medications have been found to come from many classes of medications including neuronal stabilizing agents (aka anticonvulsants), antidepressants, antihypertensives, and antihistamines. Some effective preventive medications include Elavil (amitriptyline), Depakote (valproate), Topamax (topiramate), and Inderal (propranolol).

## Treatment

MOH is common and can be treated. The overused medications must be stopped for the patient's headache to resolve, though there is limited evidence to suggest this can be done without using other preventive measures. Clinical data shows that the treatment of choice is abrupt drugs withdrawal, followed by starting prophylactic therapy. However, the discontinuation of overused drugs may lead to the initial worsening of headaches, nausea, vomiting, sleep disturbance, anxiety, and restlessness. These symptoms greatly depend on the previously overused drugs and typically last from two to ten days. They are relieved by the further intake of the overused medication, which might reinforce the continuation of overuse and noncompliance toward discontinuation. Where physical dependence or a rebound effect such as rebound headache is possible, gradual reduction of medication may be necessary. It is important that the patient's physician be consulted before abruptly discontinuing certain medications as such a course of action has the potential to induce medically significant physical withdrawal symptoms. Abruptly discontinuing butalbital, for example, can actually induce seizures in some patients, although simple over the counter analgesics can safely be stopped by the patient without medical supervision. A long-acting analgesic/anti-inflammatory, such as naproxen (500 mg twice a day), can be used to ease headache during the withdrawal period. Two months after the completion of a medication withdrawal, patients with MOH typically notice a marked reduction in headache frequency and intensity.
Drug withdrawal is performed very differently within and across countries. Most physicians prefer inpatients programmes, however effective drug withdrawal may also be achieved in an outpatient setting in uncomplicated MOH patients (i.e. subjects without important co-morbidities, not overusing opioids or ergotaminics and who are at their first detoxification attempt). In the absence of evidence-based indications, in MOH patients the choice of preventive agent should be based on the primary headache type (migraine or TTH), on the drug side-effect profile, on the presence of co-morbid and co-existent conditions, on patient's preferences, and on previous therapeutic experiences.
Following an initial improvement of headache with the return to an episodic pattern, a relevant proportion (up to 45%) of patients relapse, reverting to the overuse of symptomatic drugs.
Predictors of the relapse, and that could influence treatment strategies, are considered the type of primary headache, from which MOH has evolved, and the type of drug abused (analgesics, and mostly combination of analgesics, but also drugs containing barbiturates or tranquillisers cause significantly higher relapse rates), while gender, age, duration of disease and previous intake of preventative treatment do not seem to predict relapse rate.
MOH is clearly a cause of disability and, if not adequately treated, it represents a condition of risk of possible co-morbidities associated to the excessive intake of drugs that are not devoid of side-effect. MOH can be treated through withdrawal of the overused drug(s) and by means of specific approaches that focus on the development of a close doctor-patient relationship in the post-withdrawal period.

## History

Rebound headache was first described by Dr. Lee Kudrow in 1982.