Clinical Review

Chronic headache: Stop the pain before it starts

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Less common primary headache disorders
Hemicrania continua, a rare cause of chronic daily headache, is unilateral, without shifting sides, and the intensity is moderate to severe—and unrelenting. HC is associated with autonomic features such as lacrimation, ptosis, and nasal congestion.

New daily persistent headache is characterized by an out-of-the-blue onset of a headache that becomes unremitting soon after it develops. To receive a diagnosis of NDPH, the patient must have a headache that started suddenly and has continued for 3 months or more.

Most patients diagnosed with NDPH are able to recall, to the day, when the headache started. More than 50% report a precipitating event, such as a viral illness, a stressful experience, or surgery.15 ICHD-II defines NDPH as having the characteristics of a tension headache. Notably, however, migrainous features are also common, and neurologists often diagnose NDPH with either migrainous or tension-type features.16

The sudden onset of NDPH is a red flag and, like other red flags, always warrants further work-up. Magnetic resonance imaging with gadolinium is preferred to computed tomography. Magnetic resonance venography or lumbar puncture may also be considered.15,16

Review comorbidities, rule out secondary causes
Patients who suffer from frequent headaches have a high prevalence of depression, anxiety,17,18 sleep disorders,19 obesity,20 irritable bowel disease, fibromyalgia,21 temporomandibular joint disorder,22 and chronic fatigue syndrome. Treatment of these disorders may increase the efficacy of headache treatment. Conversely, overuse of headache medications can make comorbidities harder to treat.

Treating chronic headache: Which drugs are best?
A multimodal approach combining pharmacologic and nonpharmacologic therapies is usually required for patients with chronic headache. The particular therapy and prognosis depend on the type of headache a patient has and the presence of comorbidities (TABLE 3).6,7,23,24

Consider comorbidities in prophylaxis selection6,7,23,24

ComorbidityWhat to chooseWhat to avoid
Bipolar disorderValproic acidVenlafaxine, amitriptyline, mirtazapine
Insomnia (CM)Amitriptyline
Insomnia (CTTH)Mirtazapine
HypertensionMetoprolol, propranolol
Cardiac conduction abnormalitiesAmitriptyline
FibromyalgiaAmitriptyline, tizanidine
CM, chronic migraine; CTTH, chronic tension-type headache.

Choice for migraine prophylaxis? Here’s what the evidence tells us

Although most studies of the benefits of prophylaxis have involved patients with episodic or frequent migraine rather than CM, extrapolation of the findings to patients with CM is not unreasonable. And, although dozens of pharmacologic and complementary therapies have been studied for migraine prophylaxis and certain classes of drugs have been identified as effective, there are very few head-to-head trials comparing agents.

The American Academy of Neurology and the American Headache Society published a summary of the evidence in 2012.23 Key findings: The types of medication with the most evidence to support their use as first-line agents for CM are antidepressants, anticonvulsants, and beta-blockers.

Antidepressants, especially tricyclics (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), have been found to be effective. Chief among them are amitriptyline, a TCA, which is inexpensive and may be beneficial for patients with coexisting insomnia due to its sedating effect, and venlafaxine, an SNRI, which may help treat comorbid depression.23 Amitriptyline is associated with weight gain and can prolong the QT interval at higher doses. There is insufficient or conflicting evidence of the value of selective serotonin reuptake inhibitors for migraine prophylaxis.

Anticonvulsants that have been studied most extensively for migraine are topiramate and sodium valproate. Both have level A ratings for established efficacy.23 Topiramate has also been shown to be noninferior to amitriptyline in reducing migraine frequency and is associated with weight loss, rather than weight gain.25 (Topiramate and valproic acid should be avoided in women who are hoping to become pregnant.) Gabapentin has conflicting evidence and is not recommended for migraine.23

Beta-blockers that appear to be most effective as prophylaxis for CM are propranolol, metoprolol, and timolol.23,26 Any of these would be the obvious choice for a patient with comorbid hypertension. Beta-blockers can take several months to have an effect on migraines, however. Their use as CM prophylaxis may be limited by their adverse effect profile, which includes erectile dysfunction, bradycardia, and hypotension, although the lower dosage needed for migraine prophylaxis may be a mitigating factor. Calcium channel blockers are commonly prescribed for migraine, but there is little evidence to support their use for CM.23

Other medications that are likely effective for migraine prophylaxis include naproxen24 and tizanidine27 (a muscle relaxant). Complementary and alternative treatments that appear to be effective include magnesium, feverfew, butterbur, and riboflavin, although the benefits may not be noticeable for several months.24

Botulinum toxin A is the only medication approved by the US Food and Drug Administration for prevention of CM. It is generally considered to be a second-line agent because of its high cost and the need for training and expertise to administer it. Botulinum toxin A is not effective as prophylaxis for EM.28


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