Headache - FMBR 2nd Edition

Educational Objectives

Program Objectives

Upon completing this educational activity, participants will be better able to:

1. Understand and appropriately respond to the wide range of medical and psychological issues frequently encountered by practicing family physicians.

2. Select relevant tests or diagnostic procedures for patients seeking care.

3. Utilize the best evidence-based knowledge to achieve optimal therapeutic goals.

4. Prescribe effective drugs and therapeutic procedures.

5. Integrate newly acquired knowledge into routine practice patterns.

Summary

Headache

Morris Maizels, MD, Family Physician, Carolina Headache Institute; Founding President, Southern Headache Society, Chapel Hill, NC

Features of worrisome headaches: while most headaches have benign causes, the consequences of missing a secondary headache can be devastating; systemic symptoms, neurologic signs, sudden or dramatic onset, onset at >50 yrs of age, change in pattern (SNOOP) — mnemonic summarizing indications a headache may have a more serious cause; systemic symptoms include fever, weight loss, cough, history of malignancy, and pregnancy (a hypercoagulable state); neurologic signs and symptoms can indicate a tumor, although ≥8% of patients diagnosed with brain tumors present with headache as an isolated symptom; since most brain tumors present with subtle symptoms of neurologic dysfunction (eg, changes in behavior or personality), it is important to perform a neurologic examination with fundoscopy during initial evaluations; sudden or dramatic onset is exemplified by a thunderclap headache (which reaches peak intensity within seconds), but may also refer to a first or worst headache, or headaches causing nocturnal awakening (although these commonly occur with migraines and medication overuse headaches [MOH]); in patients who present with onset of new headache at >50 yrs of age, potential neurologic causes and giant cell arteritis are a concern; any change in the pattern of a previously stable headache (eg, increased frequency or severity) can warrant concern

Features suggestive of benign causes: triggers of onset include alcohol, foods, odors, or a hormonal pattern; relief of headache occurs with sleep

Response to medication: does not preclude diagnosis of secondary headache (in numerous case reports document headaches of an ominous nature in patients who responded to sumatriptan)

Guidelines for imaging: the American Academy of Neurology does not recommend imaging for typical cases of episodic migraine (ie, headaches not occurring on a daily basis; note that many patients do not report their headaches as occurring daily unless specifically asked), and has not issued guidelines for other primary headaches (eg, chronic migraine [daily or near-daily], chronic tension-type headache, or cluster headache [CH]); when imaging is indicated, the computed tomography (CT) head scan is primarily useful to rule out bleeding, or when an urgent scan is needed; magnetic resonance imaging (MRI) — indicated for chronic headaches; offers better visualization of smaller lesions and the posterior fossa (important for diagnosis of Chiari malformation); although contrast agents are not required for typical screenings, the use of contrast is indicated when assessing for demyelinating lesions or dural enhancements (seen in, eg, low-pressure headaches), and when further definition of an abnormality seen on a routine MRI is needed; magnetic resonance angiography (MRA) and magnetic resonance venography MRV — MRA is indicated with suspicion of an aneurysm or arterial dissection; MRV is indicated with suspicion of cerebral venous thrombosis is suspected (most typically during the evaluation of thunderclap headache or pseudotumor cerebri); thunderclap headache — some experts recommend combination of MRI, MRA, and MRV, as potential causes include aneurysmal dissection and central venous thrombosis

Lumbar puncture (LP): measurement of opening pressure via LP is required primarily in high- and low-pressure headaches that are not visible in routine imaging

Diagnosis of Primary Headache

Data on episodic headaches from the Landmark study (2002): indicated that 95% of episodic headaches can be attributed to migraines; derived from headache diaries kept by 1200 adult patients from 128 practices in 15 countries; the diagnosis of migraine was correct in 98% of instances; among patients whose headaches were initially diagnosed by a primary care physician as having a non-migraine cause, 82% were eventually confirmed to have migraines; additionally, 90% of patients initially diagnosed with sinus headaches were eventually diagnosed with migraines

Common sources of misdiagnosis: neck tension or pain (manifests as a component of headache in most patients with migraines, and often occurs before the onset of headache; neck pain typically resolves along with the headache, or with treatment [ie, triptans]); stress-related triggers — patients who complain of stress are often misdiagnosed as having tension headaches; however, stress is a common trigger of migraines

Formal classification of headache disorders: initially based on duration; headaches lasting >4 hrs — constitute the overwhelming majority of headaches seen in primary care settings; potential causes include migraines, tension-type headaches, and (less commonly) new daily persistent headache; headaches lasting <4 hrs — often more severe than headaches associated with shorter durations; potential causes include CH and (rarely) trigeminal autonomic cephalgias; frequency — secondary classification (after duration); episodic migraines occur ≤15 days per month, while chronic migraine occurs >15 days per month; thus, a diagnosis of chronic migraine refers to the frequency of headache, rather than how long the patient has had the problem; the distinction between episode and chronic is crucial, as certain treatments are indicated only for chronic migraines (eg, onabotulinum toxin A [Botox])

Diagnosis of migraines: due to a lack of biologic markers, migraines are diagnosed via an agreed-upon set of clinical criteria; severe, unilateral, throbbing, worsening with activity, nausea, sensitivity to light and sound (SULTANS) — mnemonic describing diagnostic criteria for migraines; diagnosis requires 2 of the initial 4 pain-related criteria (severe, unilateral, throbbing, and worsening with activity), plus 1 of the 2 secondary criteria related to autonomic phenomena (nausea or sensitivity to light and sound); other diagnostic features — in adults, migraine headaches typically last 4 to 72 hrs; in children, migraines often last <4 hrs; perceptions of auras is not a diagnostic requirement, as they are only seen by ≈16% of migraineurs; family history of migraine is not a criterion; location criterion only specifies that the headache occurs unilaterally, although some patients experience their headache in an occipital (rather than frontal) location; history — diagnosis requires a recurring pattern of ≥5 attacks; an individual presenting a new-onset headache might still warrant evaluation for worrisome underlying causes (even if their headache meets all SULTANS criteria)

New daily persistent headache (NDPH): refers to headache with sudden onset that never resolves; may develop features associated with migraines, but often does not; these headaches are notoriously unresponsive to standard treatments, and patients with this condition typically merit referral

Headaches due to abnormalities of cerebrospinal fluid pressure: include high-pressure headaches (ie, idiopathic intracranial hypertension, pseudotumor cerebri) and low-pressure headache (ie, spontaneous intracranial hypotension); potentially missed by routine diagnostic imaging, and are only definitively diagnosed via LP

Cluster headache: most common cause of headaches lasting <4 hrs; often misdiagnosed as migraines; extremely severe, and sometimes known as “suicide headaches”; occurrence is strictly unilateral, and typically associated with tearing of the eye, rhinitis, and other autonomic symptoms occurring ipsilateral to the headache; attacks typically occur on a bi-daily basis for weeks or months, before remitting for months or years (although there is a chronic form that never remits); easily distinguished from migraine based on duration (CH typically resolves within 3 hrs, and often within 30 min); other distinguishing features — clock-like regularity of onset (patients often report headaches awakening them from sleep at the same time each night); restlessness and agitation during attacks (whereas migraine patients prefer to rest); more common in men (vs migraine, which is more common in women)

Acute and Symptomatic Treatment of Migraines

Triptans: all 7 currently approved triptans are generally comparable in efficacy and tolerability, but their mode of delivery significantly influences efficacy; like all other acute migraine therapies, they have the highest efficacy when taken early in the attack; subcutaneous sumatriptan — has the highest efficacy in speed of onset; underutilized in primary care; recommended for patients whose headaches have an extremely rapid onset headache, are present upon awakening, or do not otherwise respond to oral agents; sumatriptan plus naproxen — combination has shown superiority to monotherapy with either agent; many clinicians advise patients to use a combination of the two ingredients, rather than prescribing the fixed combination

Contraindications to the use of triptans: include a history of cardiovascular or cerebrovascular disease; chest pain is a common side effect of triptans, and although the nature of this chest pain has not been clearly determined in the majority of cases, it is not cardiac in nature; in individuals with significant risk factors or with prolonged or severe attacks of chest pain, a cardiac work-up may be indicated (although guidelines for the extent of these evaluations have not been developed); hemiplegic or basilar migraine — ie, a migraine whose aura includes neurologic symptoms that may mimic a stroke

Dihydroergotamine (DHE): an underutilized therapy in the migraine armamentarium; available in nasal and intramuscular formulations (an inhaled form is pending approval); particularly useful for the management of prolonged attacks (including status migrainosus)

Symptomatic medications: potentially useful for patients who cannot tolerate triptans, or have milder attacks; numerous studies document the efficacy of nonsteroidal anti-inflammatory medications, with most studies having assessed ibuprofen or naproxen; a sachet of rapidly dissolving diclofenac has been approved for the acute treatment of migraine; fixed combination products containing aspirin, acetaminophen, and caffeine also have documented efficacy, but have been strongly associated with the development of MOH; aspirin — 1000 mg doses showed efficacy comparable to sumatriptan in Cochrane database review; may be combined with 10 mg of metoclopramide to improve the relief of nausea; note that many of the studies demonstrating aspirin’s efficacy used dissolvable tablets; paracetamol — less effective than aspirin, but may be effective when combined with metoclopramide

Medication Overuse Headache

Background on MOH: ie, drug rebound headache; a controversial entity, but an important consideration with all acute migraine medications; defined as a daily headache that develops after using acute medications for periods of >10 to >15 days over a prolonged length of time; most commonly associated with over-the-counter combination products containing caffeine, opiates, and medications containing butalbital; however, analgesics and triptans may also cause MOH

Management of MOH: since patients are not necessarily forthcoming about their total consumption of medications, it is important to precisely determine the quantity of acute remedies used by the patient; patients using symptomatic medicines on a daily basis must withdraw from these agents before starting regimens of preventive medications, and usually require referral for specialty care; brief use of bridge therapy (which may include an anti-inflammatory, corticosteroid, or other non-narcotic agent) is typically initiated to allow the patient to withdraw from medications causing MOH; parenteral ketorolac may be used as rescue therapy in an office, urgent care, or emergency department setting; combination parenteral therapies which include antiemetics (eg, metoclopramide or prochlorperazine) are often effective; oral or parenteral corticosteroids is common in emergency settings, but there is little evidence to support their use

Prevention of Migraines

Preventive therapies: 4 oral medications have been approved for the preventive treatment of migraine (propranolol, timolol, divalproex sodium, and topiramate); onabotulinum A toxin is the only agent approved specifically for the treatment of chronic migraine; other agents are commonly used off-label for the prevention of migraines (particularly antidepressants)

General principles of preventive therapy: selection of regimens is typically based on the patient’s comorbidities and the side effect profile of individual agents, as no preventive agent has superior efficacy; concern for weight gain is particularly important; class-related distinctions — tricyclic antidepressants (TCA) are effective, but selective serotonin reuptake inhibitors typically are not; topiramate and valproate are effective anti-epileptic medications, but gabapentin is not; comorbidities — although it is tempting to use 1 medication to treat headache and the common comorbidity of depression, it is recommended to select the best agent targeting a single condition, and add-on medications as needed; depression often improves when headaches improve, although there is no evidence the treatment of depression influences outcomes related to headache; anxiety disorders have an even higher comorbidity with migraine (compared to depressive disorders), and are clinically important to address; dose and duration — “start low and go slow”; for TCAs, begin at 10 mg and increase weekly up to 50 mg; it is important to titrate to maximally tolerated doses, as inadequate dosing is a common cause of treatment failure; it is also important to allow adequate time for a treatment response, which may require ≤3 mo

Antidepressants: amitriptyline has the best documented evidence of efficacy, although its side effect profile includes significant weight gain, sedation, and anticholinergic effects; nortriptyline (metabolite of amitriptyline) causes less sedation and fewer anticholinergic side effects, and is often better tolerated; electrocardiography (EKG) monitoring for QT prolongation may be indicated for patients receiving doses of >75 mg; measuring plasma levels of amitriptyline or nortriptyline may be useful in guiding therapy for a patient who is not responding; venlafaxine and duloxetine — serotonin-noradrenergic reuptake inhibitors (SNRI); have a different side effect profile than the tricyclics, as they do not typically cause sedation and weight gain; however, discontinuation can cause a withdrawal syndrome, and patients should never abruptly discontinue venlafaxine; SSRIs — not particularly effective at preventing migraines; however, they may be useful in patients with comorbid anxiety or depression

Anti-epileptics: the popularity of topiramate has increased due to its association with weight loss; a typical titration schedule begins with 25 mg at night, and increases by 25 mg per week (up to 100 mg); the most common side effect of topiramate is tingling in the fingers and toes, but the most troubling side effect is cognitive impairment (typically involves difficulty with word finding or name recall); at doses >100 mg, topiramate may interfere with absorption of combined (progesterone plus estrogen) OC pills; since topiramate is associated with a slight increase in renal stones, a history of renal stones is a relative contraindication; associated with rare occurrences of acute glaucoma syndrome (typically occurs soon after initiation of therapy); valproate — use is limited by its side effect profile (includes weight gain, hair loss, and tremors); due to teratogenic effects, it is typically avoided in women of childbearing age; potentially recommended in women beyond childbearing age for whom weight is not an issue, or men and women with bipolar disorder

β-blockers: effective; approved for episodic migraines, at doses within the same range typically used for treating hypertension and cardiac conditions; may be prescribed on a PRN basis for use before exercise (in patients whose migraines are triggered by exercise)

Calcium channel blockers: eg, verapamil; potentially helpful in some patients

Other preventive treatments: lisinopril (angiotensin converting enzyme [ACE] inhibitor) and candesartan (angiotensin receptor blocker) may be useful as adjuncts; natural supplements (eg, vitamin B2, coenzyme Q10, butterbur root) have documented efficacy as migraine preventives; although acupuncture failed to show benefits superior to “sham acupuncture” in trials, the speaker avoids discourage its use; mindfulness practices and yoga may have benefits, especially in individuals who seem to have significant contributions from stress in their lives

Onabotulinum toxin A: specifically approved for the treatment of chronic migraine (>15 days a month of headache, with ≥8 of those days including migraine-like symptoms), despite failing to show superiority over placebo in clinical trials; overall efficacy is no greater than other preventives; possibly effective for individuals with MOH; use requires specialized training; advantages include a relative lack of side effects (other than local cosmetic side effects, local pain, and occasionally, temporary weakness of the neck muscles)

Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP): entirely new family of migraine preventives currently under development; first agent in this class is expected for release in 2018

Hormone therapies: menstruation is the most common trigger of migraines in women, and associated migraines may be particularly severe; menstrual migraine — refers to a headache that has on set during the perimenstrual period (defined as 2 days before and ≤3 days after the onset of menstruation); attributed to a decline in serum estradiol levels occurring shortly before and during the perimenstrual phase; a similar (but smaller) drop in estrogen occurs mid-cycle, and may lead to mid-cycle migraines; treatment approaches for menstrual migraine — daily low-dose OC (preferably containing ≤20 mcg of estrogen) without monthly withdrawal (ie, placebo pills allowing menstruation); etonogestrel-ethinyl estradiol vaginal ring (NuvaRing) with continuous hormone exposure; stroke risk and migraine with aura — the World Health Organization recently issued a recommendation discouraging the use of OCs in women who have migraines with aura, due to an increased risk for strokes seen in women with this condition; however, this recommendation was based on older studies where women more commonly received OCs containing higher doses of estrogen (ie, ≥50 mcgs); recent review of evidence suggests low-dose OCs only increase the risk for stroke in this population when combined with smoking or hypertension; however, most board review tests still include migraine with aura as a contraindication against the use of OCs

Lifestyle measures: regular sleep habits; aerobic exercise; stress reduction; reducing caffeine to ≈1 cup of coffee or its equivalent per day; dietary triggers — speaker regards these as over-emphasized, since most patients who report a dietary trigger associated with migraines do not respond to that trigger when assessed in a controlled setting

Readings

Disclosures

For this activity, members of the faculty and planning committee reported nothing to disclose. In this lecture, Dr. Maizels presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FMBR170129

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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