HEADACHE UPDATE: Expanding Our Horizons

Allan Bernstein, MD

Headache continues to be a major cause of disability worldwide. Migraine alone affects 15–20% of the female population and 8–10% of the male population in the United States, with the greatest impact during ages 35–45, the “working years.”¹ Migraine occurs in all ethnicities and has a disproportionate prevalence in lower socio-economic groups.

While tension headaches are generally less disabling than migraine, their incidence is higher, leading to significant medication overuse. The lifelong impact of trauma, both physical and emotional, in creating new headache types and aggravating existing headache conditions is now being recognized. The economic impact of headache due to medical costs alone is over $10 billion yearly in the U.S., and that does not account for the indirect cost of time off work or working impaired, also known as “presenteeism.”²

The triptan-type medications, which are serotonin 1B/D agonists, have been available to treat migraine for over 20 years. They have proven to be relatively safe, neither triggering serotonin syndromes nor raising the incidence of cerebrovascular or cardiovascular events when used appropriately. When overused, i.e., more than 10 days a month for three or more months, they may induce medication overuse headaches and convert episodic migraine to chronic migraine. Although some triptans have become generic, their price hasn’t significantly decreased, limiting their availability to a large segment of the population.

Ergotamine, another serotonin agonist, has been used for over 50 years to treat migraine, but its strong vasoconstrictive properties and associated nausea limit its usefulness in a condition that already has nausea as a symptom. The derivative dihydroergotamine (DHE) is less vasoactive but is still associated with nausea, even in sublingual and nasal forms. A newer version of inhaled DHE is coming to the market with reports of less or no associated nausea.³

The antiepileptic medications valproate and topirimate have been used for migraine prevention with moderate success. The teratogenic risk of valproate limits its use in young women.⁴ Topirimate, in addition to causing cognitive problems in many users, may interact with oral contraceptives, reducing their efficacy.⁵

Beta blockers continue to be useful in migraine prevention, though side effects of asthma, exercise intolerance, hypotension and depression are significant drawbacks in the young population being treated.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are being reevaluated for migraine prevention. The underlying physiology is not entirely clear, but the effectiveness can be significant, with relatively few side effects. ARBs seem more effective than ACE inhibitors. with candesartan being the preferred medication.⁶ Funding for formal research on these drugs has been limited, so most data is consensus-driven.

Botox has been approved for chronic migraine, i.e., more than 15 headache days per month.⁷ It requires 15–30 subcutaneous injections per treatment, including the face, hair line around the scalp, and occipital region down to the upper trapezius muscles. It can be very effective in some individuals, but the benefit typically wears off in 10–14 weeks and needs to be repeated, potentially for years. Some insurance providers cover the cost, but Botox is currently a very expensive modality.

Calcitonin gene related peptide (CGRP) rises with the onset of acute migraine. CGRP receptor blockers and CGRP monoclonal antibodies are being investigated for both acute migraine attacks and migraine prevention.⁸ The first medication in this class, telcagepant, was studied for treating acute migraine. It produced results comparable to the triptans. Moreover, it was not vasoconstrictive and could be used in subjects with pre-existing stroke and cardiovascular disease. The development of hepatic abnormalities, however, halted further development of this drug.⁹ Other trials on related drugs have been started. Monoclonal antibodies to CGRP for the prevention of migraine have shown positive results in phase 2 testing.¹⁰ Larger trials are planned.

Local nerve blocks for acute headache have been underused. They are typically done with 0.5% bupivacaine, using 1 cc over each occipital nerve at the occipital protuberance. The relief is rapid, with no systemic side effects. The effect lasts 3–6 hours, and when the headache eventually returns, it is usually at a much lower level of intensity. Trigger-point muscle injections to both upper trapezius muscles at the same time as the occipital nerve blocks seem to increase the effectiveness of the nerve blocks.¹¹

Oxygen by mask (10 liter/min for 10 minutes) is the accepted treatment for cluster headaches, but it may also be effective for acute migraine. The vasoconstrictive properties of oxygen, along with its tendency to decelerate respiration, may be part of the effect. The safety of this treatment makes it ideal for patients who may be pregnant.

Dental disclusive devices and transmandibular joint manipulations have long been espoused by dentists and chiropractors. These treatments are typically used for acute events but are less effective for prevention. Since most physicians are unfamiliar with them, they remain underused.

The ultimate migraine medication, with the best safety record, is caffeine. It can be used preventively and during an attack. When traveling on an airplane or to altitudes over 3,000 feet, 50-100 mg of caffeine taken an hour before travel may prevent headaches. Excedrin and other AAC tablets (aspirin 500 mg, acetaminophen 500 mg, caffeine 130 mg) remain the most popular medications for treating headaches in general and migraine in particular.¹²

Migraine diets have been around for many years, but they are still not considered “real medicine.” The headache-triggering effect of red wine and carbonated alcoholic beverages is well known.¹³ Migraineurs usually learn this as teenagers. Other alcoholic beverages are less consistent in their headache-triggering capacity. Most patients are able to identify specific triggers and either eliminate them or reduce the amount used. A good example is chocolate: small amounts rarely trigger headaches, but large amounts are likely to do so. Other migraine-inducing items in diets include MSG, aspartame and pork (but not nitrates).¹⁴ Some people think gluten is a trigger, but evidence is lacking. The ketogenic diet, also known as a modified Atkins or low-carb diet, has proven useful in preventing headaches as well as seizures. The diet is currently being tested as a symptomatic treatment for Alzheimer’s disease.

Behavior modification in multiple forms is a component of comprehensive headache care. Stress management, exercise programs, yoga, Pilates and cognitive behavioral therapy (CBT) are used increasingly as more and more people try to minimize their use of medications. Biofeedback has a long history, especially locally, in the treatment of headaches of all types.^15–17

Flickering lights and bright lights in general are triggers for all types of headaches. People with low-level headaches tend to have chronic mild pupil dilation. Bright light acts as an irritant on their retinas, leading to increased headaches. Changing to incandescent bulbs with dimmer switches has reduced the frequency of headaches in many workplaces. The newer buildings with LED lighting do not seem to trigger headaches with the same frequency as those with fluorescent bulbs. Polarized sunglasses help reduce the frequency of sunlight-induced headaches.

Strong smells induce headaches in many people. The ban on scented products in medical facilities attests to the recognition of this issue. The staff may be compliant, but it is more difficult to get patients to buy in.

Sleep disorders are being recognized as triggers for headache disorders.¹⁸ Identifying and treating sleep disorders is important not only for headache management, but also for reducing the risk of heart attacks and strokes.

Neurostimulation devices represent a new wave of headache treatments. Occipital nerve stimulators have been successfully used to reduce headaches and pain for the last few years. The unit is implanted in the chest, with a wire going up the back of the neck. The day-to-day motion of the neck frequently disconnects or breaks the wires, however, making the current models less than ideal.

Transcutaneous nerve stimulation (TNS), long used to treat spinal pain, is now being used for migraine. A unit attached to a band that wraps around the forehead is the latest iteration of TNS technology.¹⁹ Headache reduction with TNS is reported to be in the 50% range, and the lack of side effects seems encouraging. The treatment is not yet covered by insurance, but its $300–$400 price range allows many patients to consider it.

A TNS device placed over the vagus nerve in the neck is being tested in Europe for migraine prevention. A transcutaneous magnetic cerebral stimulator is also being investigated.

In response to the increasing number of noninvasive and invasive approaches for treating primary headache—including hypothalamic deep-brain stimulation, occipital nerve stimulation, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct-current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation—the European Headache Federation issued a consensus statement on these neuromodulation treatments in October 2013. Their overall recommendation is “wait for better data.”

In summary, headache remains a major public health issue. There are substantial direct costs to the health care system and significant indirect costs to the affected patients, families and employers. Most current research is industry-funded and therefore directed at drugs and devices, even though there is strong evidence that behavior changes are efficacious.

Online resources for patients and medical professionals include the American Headache Society, the American Academy of Neurology and Promyhealth.org.

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Dr. Bernstein, a Sebastopol neurologist, serves on the SCMA Editorial Board.

Email: bernsteinallan@gmail.com

References
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