Frequent Headaches:​

Evaluation and Management

Anne Walling, MB, ChB, University of Kansas School of Medicine–Wichita, Wichita, Kansas

Most frequent headaches are typically migraine or tension-type headaches and are often exacerbated by medication overuse.
Repeated headaches can induce central sensitization and transformation to chronic headaches that are intractable, are dif-
ficult to treat, and cause significant morbidity and costs. A complete history is essential to identify the most likely headache
type, indications of serious secondary headaches, and significant comorbidities. A headache diary can document headache
frequency, symptoms, initiating and exacerbating conditions, and treatment response over time. Neurologic assessment and
physical examination focused on the head and neck are indicated in all patients. Although rare, serious underlying conditions
must be excluded by the patient history, screening tools such as SNNOOP10, neurologic and physical examinations, and
targeted imaging and other assessments. Medication overuse headache should be suspected in patients with frequent head-
aches. Medication history should include nonprescription analgesics and substances, including opiates, that may be obtained
from others. Patients who overuse opiates, barbiturates, or benzodiazepines require slow tapering and possibly inpatient
treatment to prevent acute withdrawal. Patients who overuse other agents can usually withdraw more quickly. Evidence is
mixed on the role of medications such as topiramate for patients with medication overuse headache. For the underlying head-
ache, an individualized evidence-based management plan incorporating pharmacologic and nonpharmacologic strategies is
necessary. Patients with frequent migraine, tension-type, and cluster headaches should be offered prophylactic therapy. A
complete management plan includes addressing risk factors, headache triggers, and common comorbid conditions such as
depression, anxiety, substance abuse, and chronic musculoskeletal pain syndromes that can impair treatment effectiveness.
Regular scheduled follow-up is important to monitor progress. (Am Fam Physician. 2020;​101(7):​419-428. Copyright © 2020
American Academy of Family Physicians.)

Patients with increasingly frequent headaches can develop Once central sensitization occurs, headaches are difficult
disabling symptoms. Biochemical, metabolic, and other to treat and cause substantial morbidity. The mean annual
changes induced by frequent headaches and/or medication cost of chronic migraine (including lost productivity and
are thought to cause central sensitization and neuronal dys- medical care) is more than three times the cost of episodic
function that results in inappropriate response to innocu- migraine (approximately $8,250 vs. $2,650).9,10 This article
ous stimuli, lowered thresholds to trigger pain response, aims to assist physicians in identifying patients at risk of
exaggerated response to stimuli, and persistence of pain escalating to chronic headache and presents an approach to
after removal of inciting factors.1-4 Together, these changes preventing such escalation. Although the literature focuses
result in increasingly frequent—and often daily—headache on migraine, the approach is applicable to other types of
and related symptoms. Each year, 3% to 4% of patients with headache.
episodic migraine or tension-type headaches (TTH) esca-
late to chronic forms.5,6 Risk Factors for Escalation from Episodic
An estimated 2% to 4% of U.S. adults have chronic head- to Chronic Headache
aches, and more than 30% of these report daily symptoms.6-8 Identifying patients with risk factors for escalating from
episodic to chronic headaches can help physicians and
patients be alert for early signs of escalation and aware
Additional content at https://​w ww.aafp.org/afp/2020/
0401/p419.html.
of the need to address modifiable risk factors, especially
CME This clinical content conforms to AAFP criteria for
medications.
continuing medical education (CME). See CME Quiz on The strongest predictive factors for headache progression
page 391. are frequent headache episodes at baseline and medication
Author disclosure:​ No relevant financial affiliations. overuse 11 (Table 1 2,7,8,11). Definitions of chronic migraine
and TTH specify that symptoms be present on at least

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 FREQUENT HEADACHES

anxiety) are associated with headache

TABLE 1 frequency and disability. It is unclear
if these are risk factors or comorbid-
Risk Factors for Escalation of Episodic Migraine ities, or if they share etiologies with
to Chronic Migraine chronic headaches.6,16 Stressful life
Risk factor Odds ratio (95% CI) Comments events are associated with increas-
ing headache frequency, especially in
Headache days per —
month* middle age.17
0 to 4 1.00 (referent)
5 to 9 7.6 (2.2 to 26.1);​P = .001 Approach to the Patient
10 to 15 25.4 (7.6 to 84.5);​P = .001 with Frequent Headaches
An algorithm for the evaluation of
Medication overuse*† —
patients with frequent headaches is
Opioids 4.4 (0.3 to 59.7)
presented in Figure 1.
Triptans 3.7 (0.8 to 16.4)
Ergotamines 2.9 (0.4 to 23.0)
Clarify Headache Type
Analgesics 2.7 (0.6 to 11.7)
and Pattern
Obesity (BMI > 30 kg 5.53 (1.4 to 21.8) May explain other associations A full assessment to clarify headache
per m2) (e.g., sleep disorders)
frequency, type, and severity takes
Diabetes mellitus 3.34 (0.96 to 12.3);​ Not significant after adjusting time, but it is an investment in suc-
P = .059 for BMI and baseline headache cessful management and may avoid
frequency
multiple patient visits and requests for
Arthritis 3.29 (1.03 to 10.5);​P < .05 Not significant after adjusting medication (Table 2).18-21 Every effort
for BMI and baseline headache should be made to accurately diagnose
frequency
each headache using criteria from
Head or neck injury Males:​3.3 (1.0 to 19.8) No relationship with severity or the International Headache Society
Females:​2.4 (1.0 to 10.8) time since injury (eTables A through E) that define dif-
ferent primary (e.g., migraine, TTH,
BMI = body mass index.
cluster headaches) and secondary
*—Highly significant in multivariate analysis adjusting for other variables.
headaches (e.g., those due to trauma,
†—Use of any headache medication on 10 or more days per month.
vascular malformations, infection,
Information from references 2, 7, 8, and 11.
or cerebrospinal fluid pressure dis-
orders). Individual patients may not
completely match criteria for a specific
15 days per month, but central sensitization may occur at headache diagnosis and may have more than one type of
lower frequencies.5 Migraine may have a threshold for cen- headache.5 The POUND mnemonic can be useful in the
tral sensitization of four episodes per month.1,11 Symptoms diagnosis of migraine 22,23 (Table 322).
predictive of migraine escalation are pulsating quality, History. As headaches become more frequent, patients
severe pain, photophobia, phonophobia, and attacks lasting often have difficulty recalling details. A headache diary can
longer than 72 hours.12 Long attack duration and nausea help document date, duration, symptoms, treatment, and
are predictive of development of chronic TTH.13 Cutane- outcome of each headache episode, in addition to suspected
ous allodynia is strongly associated with chronification triggers or other patient observations.18-21,24,25 Patients with
and may be a marker of central sensitization.13,14 The high- migraine are often hyperresponsive to causes of secondary
est medication-associated risk is with opioids, followed by headaches.5 A diary may identify an overlooked cause of
triptans, ergotamines, and nonopioid analgesics.7,11 secondary headaches or a recurrent trigger for migraine
Chronic pain, especially musculoskeletal pain, and obe- episodes.
sity are strongly associated with chronification.15 Associa- The history should cover the patient’s typical headaches
tions with snoring, sleep disorders, diabetes mellitus, and as well as recent changes. The current headache diagnosis
arthritis lose significance when controlling for body mass may be inaccurate, incomplete, or undergoing transition.
index and headache frequency.11 Several psychiatric con- In studies, migraine was the correct diagnosis in 82% of
ditions (e.g., major depressive disorder, bipolar disorder, patients previously diagnosed with nonmigraine headaches

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 BEST PRACTICES IN NEUROLOGY

Recommendations from the Choosing Wisely Campaign

Sponsoring
Recommendation organization in older adults, pregnant women, and
patients with cancer or other immuno-
Do not recommend prolonged or frequent use of over-the- American Headache
counter pain medications for headache. Society
compromising condition.32
Decisions about imaging in patients
Do not prescribe opioid or butalbital-containing medications American Headache with increasingly frequent migraine
as first-line treatment for recurrent headache disorders. Society
or TTH are challenging.18-21,24,30-32 U.S.
Do not perform neuroimaging studies in patients with stable American Headache headache guidelines recommend mag-
headaches that meet criteria for migraine. Society netic resonance imaging with and
without contrast for patients with pro-
Do not perform computed tomography imaging for head- American Headache
ache when magnetic resonance imaging is available, except Society gressively worsening headaches over
in emergency settings. weeks to months because of the remote
possibility of subdural hematoma,
Source:​ For more information on the Choosing Wisely Campaign, see https://​w ww.
choosingwisely.org. For supporting citations and to search Choosing Wisely recommenda- hydrocephalus, tumor, or another
tions relevant to primary care, see https://​w ww.aafp.org/afp/recommendations/search.htm. progressive intracranial lesion.18
Nevertheless, without neurologic

and in 88% of patients diagnosed with sinus

FIGURE 1
headaches.26,27 Patients often describe more than
one type of headache. More than 80% of those Identify most probable headache diagnosis or diagnoses
with confirmed migraine also have TTH, and
patients with any primary headache may develop
superimposed secondary headaches.28 Assess for serious underlying condition

The history may detect symptoms of progres-

sion to chronic headache. Patients who develop
chronic migraine typically report progres-
High probability Low probability
sively frequent bilateral frontotemporal TTH-
type symptoms with superimposed full-blown
migraine attacks. Sleep and emotional distur- Urgent
assessment and
bances are common.12,29 Patients developing intervention Probable migraine Probable trigem- Diagnosis
chronic TTH or medication overuse headaches or tension-type inal autonomic unclear
headache cephalalgia
(MOH) often have nonspecific headaches.
Physical Examination. Between headache
episodes, physical examination is usually nor- Assess for medication Imaging Reassess
mal in patients with frequent migraine, TTH, overuse headache; and consider
treat if present consult
and other primary headaches. Guidelines rec-
ommend neurologic assessment and physical
examination of the head and neck, focusing on
any potential source of secondary headaches
(Table 2).18-21 Implement individualized management plan
Imaging. Guidelines recommend magnetic • Acute and prophylactic medications

resonance imaging with and without contrast in • Behavioral and physical therapies
• Counsel patient about adherence and appropriate medication use
patients with trigeminal autonomic cephalalgias
• Reduce risk factors, triggers, and exacerbating factors
(e.g., cluster headache, paroxysmal hemicrania,
• Promote healthy lifestyle
hemicrania continua, short-lasting neuralgiform • Manage comorbidities
headache), headaches with new features or neu- • Provide headache education for patient and family members
rologic deficits, or suspected intracranial abnor-
mality.30-32 The American College of Radiology
recommendations can help guide imaging for var- Monitor and follow up
ious headache presentations, headaches in specific
locations (e.g., base of skull, orbit, sinuses), and Diagnostic approach to the patient with frequent headaches.
investigation of specific conditions, and imaging

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 FREQUENT HEADACHES

findings, relevant results from neuro-

TABLE 2 imaging are reported in less than 1%
of patients who have frequent episodic
Assessment of Patients with Frequent Headache migraine.23 Other imaging modalities
Headache history such as positron emission tomogra-
Associated symptoms (especially nausea, vomiting, fatigue, photo- or phonophobia, phy, single-photon emission computed
head or neck tenderness, autonomic symptoms, or allodynia)
tomography, electroencephalography,
Beliefs about cause, appropriate management, and prognosis;​goals for management
and transcranial Doppler ultraso-
Coping mechanism, effects on quality of life, and support system
nography are not recommended in
Duration of episodes
patients with frequent headaches.31
Exacerbating and relieving factors (e.g., activity, light and noise avoidance, sleep)
Frequency of episodes and change in pattern RULE OUT SERIOUS UNDERLYING
Intensity of pain (1 to 10 scale) CONDITIONS
Medications used and effectiveness (name and dosage for all prescription and Serious pathologic conditions are
nonprescription medications)
uncommon causes of frequent head-
Pain location
aches, but they must be considered,
Pattern and rate of onset, peaking, and resolution of symptoms
even in patients with confirmed pri-
Precipitating or associated events (triggers, prodromes)
mary headaches. Expert groups list
Previous assessments, diagnoses, and treatments
different red flag warning features.
Quality of pain (e.g. throbbing, pulsating, squeezing, splitting)
The SNNOOP10 mnemonic describes
Additional history symptoms that should raise suspicion
Evidence of common comorbidities (e.g., depression, anxiety, posttraumatic stress for serious underlying pathology in
disorder, substance or alcohol misuse, chronic pain) patients with headache (Table 4).33
Risk factors for conversion to chronic headache (Table 1) The probability of a significant lesion
Signs or symptoms of serious secondary headache (Table 4) is most strongly associated with
cluster-type headache symptoms,
Physical examination
abnormal neurologic examination,
General impression, vital signs (pulse, blood pressure, temperature)
poorly defined headache, and head-
Head:​temporal artery firmness/tenderness (in older patients), sinus tenderness
aches associated with aura, the Val-
Neck:​posture, range of motion, muscle tenderness
salva maneuver, or exertion.23
Neurologic:​general assessment of mental status;​cranial nerve examination, including
fundoscopy;​pupils;​eye movements;​visual fields;​facial power and sensation;​soft
palate and tongue movements;​limb power;​tone;​coordination;​reflexes;​gait, includ- ASSESS FOR MEDICATION OVERUSE
ing heel-toe walking (tandem gait);​plantar responses Addressing medication overuse may
Other assessments as indicated by symptoms, medical history, or risk factors be the most important intervention for
Diagnostic testing
increasingly frequent headaches.18-21,34
About 30% to 50% of patients who
Imaging:​not recommended unless patient has red flag symptoms (Table 4), trigemi-
nal autonomic cephalalgias, or atypical headache, or to diagnose specific suspected develop chronic headaches have
underlying disorder MOH,6,8,35,36 which is defined as head-
Laboratory testing as indicated to identify underlying condition in patients with sec- ache on 15 or more days per month
ondary headache (e.g., erythrocyte sedimentation rate for temporal arteritis) in a patient with preexisting primary
Other assessments
headache, developing as a conse-
Headache diaries
quence of regular overuse of acute or
Measures of headache effects and disability (e.g., Headache Impact Test*) to assess
symptomatic headache medication
quality of life and track progress for more than three months.5 Over-
Screening tools for comorbidities (e.g., Patient Health Questionnaire-9 for depres- use is defined as 15 or more days per
sion†, CAGE questionnaire for alcohol use‡) month for nonopiate analgesics and
*—Available at http://​w ww.migraineresourcenetwork.com/images/assessment_tools/HIT-6.pdf.
10 or more days per month for ergot-
†—Available at https://​w ww.mdcalc.com/phq-9-patient-health-questionnaire-9. amines, triptans, opioids, and combi-
‡—Available at https://​w ww.mdcalc.com/cage-questions-alcohol-use. nations of drugs from more than one
Information from references 18-21. class.5 MOH usually resolves after
stopping overuse, but this is no longer

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 FREQUENT HEADACHES

required for diagnosis.5 MOH devel- is inconsistent.41-43 Rapid outpatient

ops almost exclusively in patients with TABLE 3 withdrawal is generally recommended
migraine or TTH. Nonopioid anal- for nonopioid analgesics (includ-
POUND Mnemonic for the
gesics are the most commonly impli- ing nonsteroidal anti-inflammatory
Diagnosis of Migraine
cated medications because of their drugs, acetaminophen, and aspirin),
widespread use in headache treatment;​ Pulsating or throbbing pain ergotamines, and triptans. Inpatient
however, triptans are an increasingly One-day average duration tapered withdrawal is recommended
common cause of MOH in the United Unilateral location for patients taking opiates, barbitu-
States. The estimated mean critical Nausea or vomiting rates, or benzodiazepines;​those with
Disabling
dose and duration of use for triptans significant comorbidities;​and those in
are 18 doses per month and 1.7 years, Note:​Probability of migraine in a pri- whom previous outpatient withdrawal
compared with 114 doses per month mary care patient is 92% when 4 POUND was ineffective.18-20,35,41 Recommenda-
symptoms are present;​64% with 3 symp-
and 4.8 years for simple analgesics. 37
toms;​and 17% with fewer than 3.
tions about pharmacologic treatment
Although not recommended and less for MOH are limited by study quality,
Adapted with permission from Ebell MH.
commonly used for headache, opioids Diagnosis of migraine headache. Am limited follow-up, poor compliance
present the greatest risk of MOH and Fam Physician. 2006;​74(12):​2088. with study medications, and difficulty
the most difficult type to treat.35,36 controlling for other factors in treat-
MOH has no classic features. Symp- ment, especially patient education
toms vary among patients and over time. Patients often and support during withdrawal.35,42,43 All studies have been
describe insidious onset of increasingly frequent head- conducted on patients with MOH and chronic migraine;​no
aches on awakening or early in the day. Headaches are guidelines are available for other patients with MOH. Euro-
of variable quality, intensity, and location. Neck pain is pean guidelines state that topiramate (Topamax), 100 to
common, and autonomic and vasomotor symptoms such 200 mg per day, is probably effective in MOH, and that
as rhinorrhea, nasal stuffiness, and vasomotor instabil- corticosteroids (at least 60 mg per day) and amitriptyline
ity are reported.35,36 Patients with MOH often have sleep (up to 50 mg per day) are possibly effective.41 A 2019 review
disturbances and psychiatric disorders, especially depres- found two studies reporting significant therapeutic advan-
sion, anxiety, and obsessive-compulsive disorder. These tage over placebo for topiramate, and one study each for
disorders usually predate MOH and may contribute to the onabotulinumtoxin A (Botox) and valproate (Depacon).35
progression to chronic headaches. 35,36,38 Diagnosing MOH In about 75% of patients with MOH, discontinuing the
depends on an accurate and detailed medication history. overused medication results in reversion to episodic migraine
Patients may underestimate their use of nonprescription or TTH;​however, the relapse rate is about 30% per year.41
analgesics or be unwilling to disclose opiate use. Screening Effective treatment for the underlying headache and close
with the questions “Do you take a treatment for attacks follow-up are essential to prevent the patient from reverting
more than 10 days per month?” and “Is this intake on a to MOH.
regular basis?” is reported to be 95.2% sensitive and 80%
specific for MOH in patients with frequent migraines.39 DEVELOP A HEADACHE MANAGEMENT PLAN
The single-question drug screen (“How many times in the Achieving prolonged symptom-free periods may be initially
past year have you used an illegal drug or used a prescrip- unrealistic, but progress in breaking the escalating pattern
tion medication for nonmedical reasons?”) is reported to of frequent headaches enables the patient and physician to
be 100% sensitive and 74% specific for detection of a drug focus on developing the most effective plan to manage epi-
use disorder in the family medicine setting.34 sodic headaches and prevent recurrent escalation. Before
The optimal strategy for medication withdrawal is unclear. initiating a management plan, the clinical features should
Guidelines stress that treatment should be individualized, be reviewed to verify the probable headache diagnosis, con-
incorporating patient education, supportive resources, and firm the absence of significant underlying conditions, and
nonpharmacologic therapies, especially in patients with identify comorbidities that could complicate management.
associated stress and chronic pain conditions. Patient edu- Consultation with a neurologist is recommended if a pri-
cation is crucial.18-20,35 In one study, 76% of patients with mary headache diagnosis cannot be confirmed, red flag
MOH were no longer overusing medications and 42% no symptoms are detected, or headaches do not improve with
longer had chronic headache 18 months after being pro- appropriate treatment.18
vided information but no other specific treatment.40 Evi- A comprehensive management plan requires pharma-
dence on the effectiveness of abrupt vs. tapered withdrawal cologic and nonpharmacologic interventions, attention

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 FREQUENT HEADACHES

to inciting and exacerbating factors, advice on

TABLE 4 healthy lifestyle, attention to comorbid con-
ditions, and education for patients and family
SNNOOP10 Mnemonic for Red Flag Symptoms members on headache management.18-20
in Patients with Headache Patients with frequent headaches require both
Sign or symptom Potential cause of headache prophylactic and acute pharmacologic treat-
Systemic symptoms (e.g., fever, Intracranial infection or nonvas-
ment.18-21 Evidence-based reviews and guidelines
rash, myalgia, weight loss) cular condition;​carcinoid tumor, provide a basis for selecting medications for indi-
pheochromocytoma vidual patients (Table 5).20,44-53 Considerations
include effectiveness, pharmacokinetics, medical
Neoplasm diagnosis (current or Brain neoplasm or metastasis
history) history, coexisting conditions, adherence, toler-
ance of adverse effects, cost and insurance con-
Neurologic deficit or dysfunction Intracranial disorder siderations, and patient beliefs about the selected
(e.g., focal deficits, seizure, cog-
nitive or consciousness changes)
agent.21 Patients with a history of MOH with one
agent should be prescribed an alternative agent
Onset sudden or abrupt* Subarachnoid hemorrhage, cranial with a lower risk of overuse. Coexisting condi-
or cervical vascular lesion
tions, especially depression and anxiety, may
Older age (> 50 years) Giant cell arteritis, cervical or intra- impair adherence and are associated with poorer
cranial lesions outcomes. Medications for headache prophylaxis
may be helpful in treating comorbid conditions
Painful eye plus autonomic Posterior fossa;​pituitary, cavernous
features sinus, or ophthalmic condition;​ (e.g., amitriptyline for depression or chronic
Tolosa-Hunt syndrome pain, propranolol for hypertension).
Guidelines stress that behavioral and physical
Painkiller overuse or new Medication overuse headache,
medication medication adverse effect or
therapies should be integrated with pharmaco-
incompatibility logic treatment of frequent headaches, but patient
access may be limited, and evidence-based guid-
Papilledema Intracranial condition, intracranial
ance is sparse.18-20,53 For migraine, relaxation
hypertension
training with or without thermal biofeedback,
Pathology of immune system HIV or opportunistic infection electromyographic biofeedback, and cognitive
behavior therapy were strongly recommended
Pattern:​new headache or Intracranial condition
change in pattern of established by the U.S. Headache Consortium based on evi-
headache dence from consistent findings in randomized
controlled trials.53 Other guidelines recommend
Position exacerbates or relieves Intracranial hypotension or
pain hypertension
stress management and acupuncture. European
guidelines for TTH recommend electromyo-
Posttraumatic onset (acute or Subdural hematoma, vascular graphic biofeedback based on a meta-analysis of
chronic) condition 53 studies.47 Cognitive behavior therapy, relax-
Precipitated by sneezing, cough- Posterior fossa or Arnold-Chiari ation training, physical therapy, and acupuncture
ing, or exercise malformation were given lower-grade recommendations because
of lack of conclusive evidence of effectiveness.47
Pregnancy or puerperium Cranial or cervical vascular condi-
tion, hypertension/preeclampsia,
Patient adherence is a major barrier to behavioral
cerebral sinus thrombosis, epidural- treatments. Key factors in adherence are negative
related headache attitudes and beliefs, lack of motivation, poor
awareness of triggers, external locus of control,
Progressive and atypical Nonvascular intracranial condition
presentation poor self-efficacy, low levels of pain acceptance,
and maladaptive coping styles.54 Self-management
*—Recurrent “thunderclap” headaches suggest reversible cerebral vasoconstric-
tion syndrome.
interventions such as cognitive behavior therapy,
mindfulness, and education are more effective
Adapted with permission from Do TP, Remmers A, Schytz HW, et al. Red and
orange flags for secondary headaches in clinical practice:​SNNOOP10 list. Neu- than usual care in reducing pain intensity, mood-
rology. 2019;​92(3):​136. and headache-related disability, but they may not
reduce the frequency of migraine or TTH.55

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 FREQUENT HEADACHES

Guidelines stress addressing the role

of lifestyle issues such as poor sleep, TABLE 5
lack of exercise, smoking, obesity, and
caffeine use in triggering and exacer- Pharmacologic Options for Treatment and
bating headaches, but the impact of Chemoprophylaxis of Primary Headache
these factors has not been quantified. Headache type Acute treatments Chemoprophylaxis*

Migraine Acetaminophen, 1,000 mg Amitriptyline, 10 to 150 mg

ENSURE FOLLOW-UP at bedtime
Acetaminophen/aspirin/caffeine,
Regularly scheduled follow-up is nec-
500 mg/500 mg/130 mg Atenolol, 50 to 200 mg daily
essary to monitor the patient’s head-
Almotriptan, 12.5 mg Candesartan (Atacand),
ache pattern and make adjustments
16 mg daily
to the management plan. Patients Aspirin, 900 to 1,000 mg
Divalproex (Depakote),
should be instructed to report signs Eletriptan (Relpax), 20 to 80 mg
250 to 750 mg twice daily
of reescalation of primary headaches, Frovatriptan (Frova), 2.5 mg
Metoprolol, 50 to 100 mg
development of MOH, or red flags for Ibuprofen, 200 to 400 mg twice daily
developing serious secondary head-
Naproxen, 500 to 825 mg Nadolol (Corgard), 80 to
aches. Factors associated with recur- 160 mg daily
rent escalation of episodic headache Naratriptan (Amerge), 1 to 2.5 mg
Nortriptyline (Pamelor), 10 to
are not clear, but poor prognosis in Rizatriptan (Maxalt), 5 to 10 mg
100 mg at bedtime
patients with chronic headache is Sumatriptan (Imitrex), 25 to 100 mg
Propranolol, 40 to 160 mg
associated with psychosocial factors, orally, 10 to 20 mg intranasally, or
twice daily
anxiety, mood disorders, poor sleep, 4 to 6 mg subcutaneously
Topiramate (Topamax), 25 to
stress, and low headache management Sumatriptan/naproxen (Treximet),
200 mg daily
self-efficacy. Based on lower-quality 85 mg/500 mg
Valproate (Depacon), 400 to
studies, other factors such as higher Zolmitriptan (Zomig), 2.5 mg orally
1,500 mg daily
patient expectations, older age, older or 2.5 to 5 mg intranasally

age at onset, headache frequency and Tension Acetaminophen, 1,000 mg Amitriptyline, 10 to 75 mg at

intensity, BMI, disability scores, and Aspirin, 500 to 1,000 mg
bedtime
unemployment are inconsistently pre- Nortriptyline, 10 to 100 mg
Diclofenac, 12.5 to 25 mg
dictive of treatment response.56 at bedtime
Several innovative medications Ibuprofen, 200 to 800 mg
are becoming available for preven- Ketoprofen, 25 mg
tion and acute treatment of migraine Naproxen, 375 to 550 mg
but have not yet been incorporated
Cluster Oxygen 100%, 7 to 12 L per minute Civamide (not available in
into evidence-based guidelines. for 15 minutes the United States), 100 mcg
Although these are valuable additions intranasally
Sumatriptan, 6 mg subcutaneously
to migraine treatment, it is important Lithium, 900 to 1,200 mg
to reconsider the diagnosis, screen Zolmitriptan, 5 mg intranasally
daily
for MOH, and address factors that Verapamil, 240 to 960 mg
could be driving headache escalation daily
before prescribing new and expensive
Rare primary May respond to indomethacin —
agents. The current expert consensus
headaches
supports the use of small-molecule
calcitonin gene-related peptide Note:​All medications are administered orally unless noted otherwise. Medication guidelines
are based on highest-grade evidence-based recommendations. 20,44-53
(CGRP) receptor antagonists (ubroge-
pant [Ubrelvy] and rimegepant *—2016 U.S. and 2018 European guidelines state that onabotulinumtoxinA (Botox) is effective
for decreasing the number and severity of headaches in patients with established chronic
[Nurtec], both of which were recently migraine, is probably effective for improving health-related quality of life in patients with estab-
approved by the U.S. Food and lished chronic migraine, and is ineffective for and should not be offered to patients with epi-
Drug Administration) and the selec- sodic migraine. 52,53

tive 5-hydroxytryptamine receptor Information from references 20 and 44-53.

1F agonist lasmiditan (Reyvow) for

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 FREQUENT HEADACHES

SORT:​KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating Comment

Physicians should conduct a complete assessment in patients C Expert consensus and several diagnostic studies
with frequent or increasing headaches—even in those with long- showing high rates of misdiagnosis of headache,
standing headaches—because a new headache type may have especially migraine and sinus headaches
developed or the current diagnosis may be inaccurate. 18-21,26,27

Neuroimaging is indicated in patients with headaches with new C Expert consensus based on concerns that intracranial
features or neurologic deficits, trigeminal autonomic cephalal- conditions can mimic unilateral autonomic symp-
gias, or suspected intracranial abnormality.18-21,30-32 toms of trigeminal autonomic cephalalgias

All patients with frequent or increasing headaches should be C Expert consensus based on multiple observational
assessed for medication overuse18-21,34 studies showing that at least 30% to 50% of patients
with chronic headache have medication overuse
headache

Prophylactic and acute therapy should be offered to patients C Expert consensus based on studies and meta-analyses
with frequent migraine, tension-type, cluster, or other primary supporting the effectiveness of prophylactic and
headache.18-21,44-52 acute therapy in reducing the number and severity of
headache episodes

Nonpharmacologic therapies such as relaxation with or without C Expert consensus supporting biofeedback in the treat-
biofeedback, cognitive behavior therapy, acupuncture, and ment of tension-type headache (meta-analysis) and
physical therapy should be incorporated in management strate- few studies supporting benefits of other modalities
gies for frequent headaches.18-20,47,53

A = consistent, good-quality patient-oriented evidence;​B = inconsistent or limited-quality patient-oriented evidence;​C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://​w ww.aafp.
org/afpsort.

treatment of acute migraine in patients who have doc- Data Sources:​ Multiple PubMed searches were completed using
umented nonresponse to or intolerance of at least two the key words headache, frequent headache, and chronic head-
ache. Information from Essential Evidence Plus was incorporated
oral triptans. Validated outcome questionnaires, such as in literature searches. Guidelines and expert recommendations
the Migraine-Treatment Optimization Questionnaire, from the American Academy of Neurology, Institute for Clinical
Migraine Assessment of Current Therapy, or Functional Systems Improvement, Scottish Intercollegiate Guidelines Net-
Impairment Scale, are recommended to document eligibil- work, American Headache Society, U.S. Headache Consortium,
ity for therapy and to monitor outcomes. and European Federation of Neurologic Societies were also
searched. The bibliographies of relevant articles were reviewed
Emerging treatments for migraine prophylaxis include to identify any primary sources missed in the original searches.
monoclonal antibodies to the CGRP receptor (erenumab Search dates:​November 2018 and January 2019.
[Aimovig]) and CGRP ligands (fremanezumab [Ajovy],
galcanezumab [Emgality], and eptinezumab). Other
agents and oral forms are in development. Indications for
Editor’s Note:​ Dr. Walling is an associate editor for Ameri-
can Family Physician.
use require confirmed diagnosis of frequent or chronic
migraine plus inability to tolerate or inadequate response
to an adequate trial of at least two prophylactic agents with The Author
established effectiveness, such as topiramate, metropro-
ANNE WALLING, MB, ChB, is professor emerita in the
lol, divalproex (Depakote), or amitriptyline. After three to
Department of Family and Community Medicine at the Uni-
six months, therapy should be continued only if headache versity of Kansas School of Medicine–Wichita.
days per month have been reduced by 50% or significant
improvement can be documented on a validated outcome Address correspondence to Anne Walling, MB, ChB, Univer-
measure, such as the Migraine Disability Assessment, the sity of Kansas School of Medicine–Wichita, 1010 N. Kansas
St., Wichita, KS 67214 (email:​awalling@​kumc.edu). Reprints
six-item Headache Impact Test, or the Migraine Physical are not available from the author.
Function Impact Diary.

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 FREQUENT HEADACHES

24. American Headache Society. Patient education:​migraines and other

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