CASE c Kelly M. Latimer, MD, MPH, FAAFP Chronic : Naval Hospital, Camp Lejeune Family Medicine Residency, North Carolina Stop the pain before it starts kelly.latimer@med. navy.mil Familiarity with the risks associated with medication The author reported no potential conflict of interest overuse and the importance of headache prophylaxis relevant to this article.

The opinions and assertions is key to easing your patient’s pain. contained herein are the private views of the author and are not meant to be construed as official or as reflecting the views of the US Navy. CASE c Eric K, age 25, is in your office, seeking help for chron- Practice ic headache—which he’s had nearly every day for the past recommendations 9 months. He says that the vary in quality and in- › Treat medication overuse tensity. Sometimes the pain is in the right temporal area; has headache by withdrawing a throbbing, pulsating quality; and is accompanied by nausea abortive therapy and initiat- and . These headaches are incapacitating, with C ing prophylactic therapy. an intensity of 10 on a scale of one to 10. When they occur, the › Select prophylactic patient reports, all he can do is take medication and medications that are first-line lie down in a darkened room for several hours, until the pain therapy for chronic migraine goes away. He cannot identify any triggers. or tension-type headache He also gets headaches that are not incapacitating, but and are appropriate for the occur almost daily, the patient says, describing a dull bilateral patient’s comorbidities. C pressure that usually begins in the afternoon and worsens un- › Advise patients to til he takes headache medication. He denies any fever, chills, limit intake of abortive weight loss, visual changes, or tinnitus. His medical history is headache medications significant only for obesity, but a system review is positive for to ≤9 per month. B depression and insomnia. Physical examination reveals normal

Strength of recommendation (SOR) vital signs; normal head, eyes, ears, nose, and throat (HEENT); and normal fundoscopic and neurological exams. A Good-quality patient-oriented evidence B  Inconsistent or limited-quality atients like Mr. K can be challenging for primary care patient-oriented evidence C  Consensus, usual practice, physicians, but referral to a neurologist is indicated opinion, disease-oriented only in the most intractable cases. For the vast major- evidence, case series P ity of patients with frequent headaches, family physicians can perform the diagnostic work-up and oversee treatment. This review will help with both.

What kind of headache? While most headaches are sporadic in nature, the preva- lence of “chronic daily headache” ranges from 3% to 5% worldwide.1-3 Chronic daily headache is not a diagnosis, however, nor is it an indication that a patient has a headache every day. According to the International Classification of Head-

126 The Journal of Family Practice | march 2013 | Vol 62, No 3 Acute headache medications should follow the “one and done” rule, eliminating the pain with a single dose.

ache Disorders (ICHD-II), chronic daily that occur ≤14 times a month—is also a risk fac- headache encompasses several distinct pri- tor for chronic headache. mary headache disorders that have a fre- ICHD-II classifies EM as a progressive quency of ≥15 times per month for at least disease that transforms to CM at a rate of 3% 3 months. These disorders are also classified per year.9 Transformation of EM to CM has by duration, as long (>4 hours) or short.4 been found to occur after as few as 5 days of The text and tables that follow focus on barbiturates or 8 days of opiates per month.10 the diagnosis and treatment of the 4 primary Patients with EM should be warned headache disorders of long duration—chron- about the potential for to become ic migraine (CM), chronic tension-type head- chronic and have their acute headache medi- ache (CTTH), hemicrania continua (HC), cations replaced with a prophylactic drug if and new daily persistent headache (NDPH) the frequency approaches 2 per week. (TABLE 1).4,5 Although medication overuse headache (MOH) is not a primary head- ache, it is included in this review because it Pinpointing the type of headache often contributes to and complicates treat- An accurate diagnosis requires a thorough ment of primary headache disorders. What’s headache history and a HEENT and neuro- more, most chronic daily headache syn- logical examination. The history should in- dromes are inextricably linked to medication clude questions about the characteristics of overuse.6,7 the headache, including the location, inten- sity, frequency, timing, associated symptoms, Which individuals are at risk? previous headache diagnoses, and triggers, Risk factors for chronic headache include fe- and address comorbidities, medication use, I mage © © mage male sex, older age, obesity, heavy caffeine caffeine intake, and family history.8 In the consumption, tobacco use, low educational absence of red flags—age >50 years, history j oe gorman oe level, overuse of abortive headache medica- of headache or systemic illness, sudden on- tions, and a history of head and neck trauma.8 set, or papilledema, among other findings Episodic migraine (EM)—that is, migraines that may indicate more serious conditions

jfponline.com Vol 62, No 3 | march 2013 | The Journal of Family Practice 127 (TABLE 2)7—advanced imaging and further z Headache with overlapping features. work-up are not needed. It is possible for a patient to have chronic headache with features of both migraine and Migraine or ? tension headache. Advise patients whose Chronic migraine. To be classified as CM, headaches have varying characteristics to the headache must have occurred ≥15 days a keep a headache journal to determine which month for 3 months or more and have features features are more prominent. Patients with of migraine, such as unilateral location, pulsat- smart phones can download a free app, such ing quality, and moderate to severe intensity. as iHeadache or My Headache Log Pro, to be Migraines are aggravated by physical activity used for this purpose.11,12 and associated with nausea and/or vomiting, photophobia, and phonophobia, and may or When to suspect medication may not be preceded by aura. Common triggers overuse headache include stress, menstruation, alcohol, skipped MOH is sometimes referred to as a rebound meals, dehydration, and chocolate. Migraines headache or drug-induced headache. Head- typically respond to ergots and triptans.4,5 aches associated with medication overuse z Partial treatment. Patients with CM have variable intensity. Patients with MOH often take medication early in the course of often awaken from sleep with a headache, a headache. This sometimes results in a par- and neck pain is highly prevalent.10 A definitive tially treated migraine that develops into a z Quantifying overuse. According to diagnosis of headache with tension-type features, such ICHD-II, overuse is defined as using a single chronic migraine as a bilateral location, a pressing quality, and abortive headache medication ≥10 times is possible only mild-to-moderate intensity, as well as a pos- a month or using 2 or more such drugs in the absence sible transformation to MOH. This is most ≥15 times a month.5 of overuse likely to occur in patients who have migraines Triptans have the potential to cause of abortive without an aura. MOH more quickly and in lower doses com- headache To avoid partial treatment, medications pared with other acute headache medi- medications. for acute migraine should be taken within cations. However, analgesics—especially 30 minutes of an attack, in a dose that’s suf- combination products such as butalbital/ ficient to relieve the pain within 2 hours, acetaminophen/caffeine (Fioricet)—are with no need for a second dose—a protocol most frequently associated with the devel- known as “one and done.” Efficacy of a triptan opment of MOH.13,14 NSAIDs have less po- can be improved by adding a nonsteroidal tential to cause MOH and are sometimes anti-inflammatory drug (NSAID).10 given as bridge therapy for patients who A definitive diagnosis of CM is only pos- are discontinuing their acute headache sible in the absence of medication overuse.4,5 medication. A patient who is overusing abortive headache medication and whose headache meets the Less common primary headache disorders criteria for CM should be given a diagnosis of Hemicrania continua, a rare cause of chronic probable CM instead. daily headache, is unilateral, without shift- z Chronic tension-type headache. In ing sides, and the intensity is moderate to se- addition to traits common to tension head- vere—and unrelenting. HC is associated with aches, CTTH may be associated with mild autonomic features such as lacrimation, pto- nausea, photophobia, or phonophobia (but sis, and nasal congestion. typically only one such feature at a time). z New daily persistent headache is There may also be tenderness to palpation characterized by an out-of-the-blue onset of of the pericranial muscles. Unlike migraine, a headache that becomes unremitting soon CTTH is not affected by physical activity. after it develops. To receive a diagnosis of Here, too, overuse of headache medica- NDPH, the patient must have a headache tion is often a factor and should be stopped, that started suddenly and has continued for if possible, before a definitive diagnosis of 3 months or more. CTTH can be made. Most patients diagnosed with NDPH are

128 The Journal of Family Practice | march 2013 | Vol 62, No 3 Chronic headache

TABLE 1 Diagnosing and treating chronic headache4,5

Type of headache ICHD-II diagnostic criteria First-line treatment Chronic migraine 1. Headache fulfilling criteria for migraine without aura Prophylactic therapy: ≥8 days/month • TCAs 2. Headache occurs ≥15 d/mo for ≥3 mo • SNRIs 3. No overuse of medication • Anticonvulsants 4. No secondary headache • Beta-blockers • Botulinum toxin A Limit acute medication; avoid triggers; initiate lifestyle modification Chronic 1. Headache fulfilling criteria for tension-type headache Prophylactic therapy: tension-type headache 2. Occurs ≥15 days/mo for ≥3 mo • Amitriptyline 3. No overuse of medication • Venlafaxine 4. No secondary headache • Mirtazapine Limit acute medication; avoid triggers; initiate lifestyle modification Medication overuse 1. Headache occurs ≥15 days/mo Discontinue overused acute meds; headache provide headache education; 2. Single abortive medication use ≥10 days/mo bridge with NSAIDs, prednisone, or combination therapy ≥15 days/mo for ≥3 mo or botulinum toxin A; 3. Headache developed or worsened during medication begin prophylactic medication overuse Hemicrania continua 1. Headache for ≥3 mo Indomethacin 2. All of the following characteristics: • Unilateral pain without side shift • Daily and continuous, without pain-free periods • Moderate intensity, but with exacerbations of severe pain 3. At least one of the following on the same side as the pain: • Conjunctival injection and/or lacrimation • Nasal congestion and/or • and/or 4. Complete response to therapeutic doses of indomethacin New daily persistent 1. Headache for ≥3 mo Rule out secondary causes; treat headache according to migrainous or tension 2. Characteristics of tension-type headache features of headache (but migrainous features are common) 3. Unrelenting from onset or within 3 days of onset 4. No medication overuse ICHD-II, International Classification of Headache Disorders; NSAIDs, nonsteroidal anti-inflammatory drugs; SNRIs, serotonin-norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants.

jfponline.com Vol 62, No 3 | march 2013 | The Journal of Family Practice 129 TABLE 2 Beyond headache: Red flags warrant additional testing7

Red flag Condition(s) to rule out Age of onset >50 y Giant cell arteritis, mass lesion, stroke No prior history of headache OR Cancer, aneurysm, stroke, cerebral sinus change in characteristic from prior headaches thrombosis, infection “Thunderclap” headache Ruptured aneurysm Signs or symptoms of systemic illness Meningitis, encephalitis, cancer (eg, fever, chills, weight loss) History of systemic illness, such as cancer, Brain metastasis, mass lesion, autoimmune autoimmune disease, or HIV meningitis, thrombosis Headache brought on by change in head position Spontaneous CSF leak or Chiari malformation or Valsalva maneuver Occipital location of headache (in children) Brain tumor Neurological symptoms Mass lesion, encephalitis Papilledema Idiopathic intracranial hypertension, cerebral sinus thrombosis Ask patients whose CSF, cerebrospinal fluid; HIV, human immunodeficiency virus. headaches have varying characteristics to able to recall, to the day, when the headache Treating chronic headache: keep a headache started. More than 50% report a precipitating Which drugs are best? journal, and let event, such as a viral illness, a stressful expe- A multimodal approach combining pharma- them know that rience, or surgery.15 ICHD-II defines NDPH cologic and nonpharmacologic therapies is there are free as having the characteristics of a tension usually required for patients with chronic head- apps for smart headache. Notably, however, migrainous ache. The particular therapy and prognosis de- phones designed features are also common, and neurologists pend on the type of headache a patient has and for this purpose. often diagnose NDPH with either migrainous the presence of comorbidities (TABLE 3).6,7,23,24 or tension-type features.16 The sudden onset of NDPH is a red flag and, like other red flags, always warrants Choice for migraine prophylaxis? further work-up. Magnetic resonance im- Here’s what the evidence tells us aging with gadolinium is preferred to com- Although most studies of the benefits of puted tomography. Magnetic resonance prophylaxis have involved patients with epi- venography or lumbar puncture may also be sodic or frequent migraine rather than CM, considered.15,16 extrapolation of the findings to patients with CM is not unreasonable. And, although doz- Review comorbidities, rule out ens of pharmacologic and complementary secondary causes therapies have been studied for migraine Patients who suffer from frequent head- prophylaxis and certain classes of drugs have aches have a high prevalence of depression, been identified as effective, there are very anxiety,17,18 sleep disorders,19 obesity,20 irrita- few head-to-head trials comparing agents. ble bowel disease, fibromyalgia,21 temporo- The American Academy of Neurology mandibular joint disorder,22 and chronic and the American Headache Society pub- fatigue syndrome. Treatment of these disor- lished a summary of the evidence in 2012.23 ders may increase the efficacy of headache Key findings: The types of medication with treatment. Conversely, overuse of headache the most evidence to support their use as medications can make comorbidities harder first-line agents for CM are antidepressants, to treat. anticonvulsants, and beta-blockers.

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TABLE 3 Consider comorbidities in prophylaxis selection6,7,23,24

Comorbidity What to choose What to avoid Depression Venlafaxine — Bipolar disorder Valproic acid Venlafaxine, amitriptyline, mirtazapine Insomnia (CM) Amitriptyline — Insomnia (CTTH) Mirtazapine — Obesity Topiramate Amitriptyline Hypertension Metoprolol, propranolol —

Cardiac conduction abnormalities — Amitriptyline Fibromyalgia Amitriptyline, tizanidine — CM, chronic migraine; CTTH, chronic tension-type headache.

z Antidepressants, especially tricyclics profile, which includes erectile dysfunction, (TCAs) and serotonin-norepinephrine reup- bradycardia, and hypotension, although the Triptans, simple take inhibitors (SNRIs), have been found to lower dosage needed for migraine prophy- analgesics, and be effective. Chief among them are amitripty- laxis may be a mitigating factor. Calcium ergots can line, a TCA, which is inexpensive and may be channel blockers are commonly prescribed be safely beneficial for patients with coexisting insom- for migraine, but there is little evidence to withdrawn nia due to its sedating effect, and venlafax- support their use for CM.23 at once or with ine, an SNRI, which may help treat comorbid Other medications that are likely effec- a slow wean depression.23 Amitriptyline is associated with tive for migraine prophylaxis include naprox- over a 4- to weight gain and can prolong the QT inter- en24 and tizanidine27 (a muscle relaxant). 6-week period. val at higher doses. There is insufficient or Complementary and alternative treatments conflicting evidence of the value of selective that appear to be effective include magne- serotonin reuptake inhibitors for migraine sium, feverfew, butterbur, and riboflavin, al- prophylaxis. though the benefits may not be noticeable for z Anticonvulsants that have been stud- several months.24 ied most extensively for migraine are topira- z Botulinum toxin A is the only medi- mate and sodium valproate. Both have level A cation approved by the US Food and Drug ratings for established efficacy.23 Topiramate Administration for prevention of CM. It is has also been shown to be noninferior to generally considered to be a second-line amitriptyline in reducing migraine frequency agent because of its high cost and the need and is associated with weight loss, rather than for training and expertise to administer it. weight gain.25 (Topiramate and valproic acid Botulinum toxin A is not effective as prophy- should be avoided in women who are hoping laxis for EM.28 to become pregnant.) Gabapentin has con- flicting evidence and is not recommended Treating other headache syndromes for migraine.23 Chronic tension-type headache. Treatment z Beta-blockers that appear to be most of CTTH applies similar principles to those effective as prophylaxis for CM are proprano- of CM, and amitriptyline and venlafaxine— lol, metoprolol, and timolol.23,26 Any of these as well as mirtazapine, a sedating SNRI— would be the obvious choice for a patient have evidence to support their use for this with comorbid hypertension. Beta-blockers type of headache.29 Overall, however, CTTH can take several months to have an effect on therapies have not been studied as exten- migraines, however. Their use as CM prophy- sively as those for migraine. There is conflict- laxis may be limited by their adverse effect ing evidence of the value of anticonvulsants

jfponline.com Vol 62, No 3 | march 2013 | The Journal of Family Practice 131 for prophylaxis of CTTH, and botulinum contributed to the escalation of his head- toxin A has been shown to be no better than aches, and ask him to stop all the headache placebo.30 medications he has been using and to keep a z Medication overuse headache. Pro- headache journal. You prescribe meloxicam phylactic medications are not effective in as a short-term bridge therapy and low-dose patients who are overusing acute headache venlafaxine, which is increased to 150 mg/d medications, and patients with MOH should over the next 4 weeks; recommend riboflavin be instructed to stop the offending drugs. 400 mg/d; and refer Mr. K to a neurologist for Withdrawal of triptans, simple analgesics, botulinum toxin A. and ergots—either cold turkey or with a slow You ask him to return in 4 weeks and ex- wean over 4 to 6 weeks—is fairly safe and can plain that because he has successfully stopped be done in an outpatient setting. Concomi- the overuse of acute headache medications, tant use of prednisone, long-acting NSAIDs, he can begin taking them again—provided or botulinum toxin A can be used as “bridge he limits their use to no more than twice therapy” to relieve acute pain. Start the pa- a week. tient on a prophylactic medication based on the best estimate of his or her baseline head- Nonpharmacologic measures can help, too ache and comorbidities.31,32 For patients who Lifestyle modification can play an important have been overusing opiates or barbiturates, role in the treatment of chronic daily head- Beta-blockers most experts recommend inpatient treat- ache. Advise patients of the importance of are an obvious ment to manage withdrawal symptoms and proper sleep hygiene, regular exercise, stress choice for prevent complications.10 reduction, and a healthy diet, as well as avoid- headache Most patients with MOH will improve ing known triggers and minimizing intake prophylaxis with drug withdrawal, but some will be left of caffeine. Tell patients that biofeedback, in patients with with the same disabling headaches that cognitive behavioral therapy, and physical hypertension, caused them to overuse medication in the therapy may play a role in conjunction with but their use first place. For such patients, weekly office pharmacotherapy, especially for CTTH,26,29,33 may be limited visits during the withdrawal period may be but that hypnosis, acupuncture, chiroprac- by their adverse helpful. After completion of the bridge thera- tic manipulation, transcutaneous electrical effects profile. py, they will likely require abortive headache nerve stimulation, and hyperbaric oxygen treatment, but its use must be limited to no have too little evidence to recommend for or more than twice a week. Referral to a spe- against their use.26,34 cialty headache clinic may be appropriate for In discussing treatment for chronic such patients. headache and the goals of therapy with a pa- z Hemicrania continua. The treatment tient with chronic headache, it is important to for HC is indomethacin. A 2- to 5-day course be frank. Explain that while a complete cure typically results in complete recovery. is not always possible, a decrease in both the z New daily persistent headache. For frequency and severity of headaches and an patients with NDPH, the first step is ruling improvement in the quality of life and the pa- out secondary causes. Once that has been tient’s ability to function are realistic goals. done, most experts recommend trying to characterize the headache as having features CASE c At the 3-month follow-up, Mr. K re- of either migraine or tension and treating ac- ports that his headaches are down to less than cordingly with preventive therapy. If acute twice a week, and that he is undergoing cog- headache medication is still needed, limit nitive behavioral therapy for depression. For the quantity you prescribe and stress the acute headache pain, he takes sumatriptan importance of taking it no more than twice 100 mg with ibuprofen 800 mg, and is careful a week. not to do so more than twice a week. JFP

CASE c Mr. K receives a diagnosis of MOH and probable CM. You explain the way MOH Correspondence Kelly M. Latimer, MD, MPH, FAAFP, Naval Hospital, develops and how his medication use has Camp Lejeune, NC 28542; [email protected]

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