Medication-Overuse Headache

Medication-overuse headache is a neurologic disorder that can cause significant disability and suffering. This condition typically only occurs in patients with migraine or tension headaches and is associated with overuse of medications for the treatment of the primary headache. Responsiveness to prophylactic therapies may also be reduced, leading to a cycle of increased medication use and increasing headache frequency and intensity. Alternative names for this condition include analgesic rebound headache, drug-induced headaches, and medication misuse headaches.

The International Classification of Headache Disorders (ICHD) defines medication-overuse headache as: “Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped.”

The prevalence of medication-overuse headache is estimated to be around 1% in the general population but may be up to 50% in specialised headache clinics.

While the pathophysiology of medication-overuse headache is not fully understood, it is thought to be related to central sensitisation. Some evidence suggests that there may also be a behavioural component, with some studies finding a higher prevalence of substance use disorders in people with medication overuse headache. Some neurobiological pathways may be common to both substance-related disorders and medication-overuse headache.

Animal models demonstrate that chronic analgesia exposure causes increased excitability in parts of the nervous system related to headache pathogenesis. This includes upregulation of calcitonin gene-related peptide (CGRP), substance P, and nitric oxide synthase in trigeminal ganglia; reduced nociceptive threshold of central trigeminal neurons; and increased susceptibility to develop cortical spreading depression.

Medications that are considered potent inducers of medication overuse headache include opioids, triptans, and ergot alkaloids. Patients may be at risk if they are taking these medications more than ten days per month. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) can also induce this disorder if taken for more than 15 days per month. Medication overuse headache can also develop in headache-prone individuals when acute headache medications are taken for other indications.

Other potential risk factors for medication-overuse headache include:

• High headache frequency at baseline;
• Age <50 years;
• Female sex;
• Anxiety or depression;
• Physical inactivity;
• Chronic musculoskeletal complaints;
• Smoking; and
• Metabolic syndrome.

Management:

The management of medication-overuse headache typically involves withdrawal of the overused medication. Patients may experience unpleasant withdrawal symptoms during this period. Symptoms will vary depending on the medicine but may include increased headache, vomiting, restlessness, sleep disturbances, and anxiety. The duration of withdrawal symptoms is typically up to four days for triptans, seven days for ergotamine, and up to ten days for analgesics. Simple analgesics, triptans, and ergot alkaloids can be discontinued abruptly without dose tapering. However, gradual dose reduction may be required for patients taking opioids or benzodiazepines.

Medications that have been overused should be avoided during the withdrawal period. However, bridging therapy may be considered, particularly for patients with severe symptoms. The Therapeutic Guidelines recommend a long-acting NSAID or a short course of prednisolone for bridging therapy, as follows:

• Naproxen modified-release tablets 750mg once daily for five days in the first week, then three to four days per week in the next two weeks, then stop; or
• Prednisolone or prednisone 50mg once daily for three days, then reduce gradually over seven to ten days to zero.

Following this, the guidelines advise that the usual acute medication may be restarted with restrictions on dose frequency (i.e. opioids and triptans to be used less than ten days a month, non-opioid analgesics for less than 15 days per month). However, it is important that these patients receive education and appropriate follow-up to reduce the risk of recurrence.

Studies support the addition of prophylactic medications for patients with primary migraine or tension headaches to return to an episodic pattern. Preventative medications with significant evidence to support them in this setting include:

• Topiramate;
• Onabotulinumtoxin A; and
• Monoclonal antibodies against CGRP (e.g. erenumab, fremanezumab).

Other prophylactic medications, such as beta-blockers, may also be considered as appropriate.

Summary

Medication overuse headache can have a significant impact on a patient’s quality of life. The accurate diagnosis of this condition is important as patients often improve following discontinuation of the overused medication. Follow-up care is important for these patients as relapse and recurrence are common.