Last updated March 14, 2022

Primary Care Management of Headache

Recommendations

Recommendation Strength
Screening and Healthcare Settings
We suggest providers assess the following risk factors for medication overuse headache in patients with headache:
·  Medication use: frequent use of anxiolytics, analgesics, or sedative hypnotics
·  Physical inactivity
·  Self-reported whiplash
·  History of anxiety or depression with or without musculoskeletal complaints and/or gastrointestinal complaints
·  Sick leave of greater than two weeks in the last year
·  Smoking
Weak for
There is insufficient evidence to recommend for or against any specific strategy or healthcare setting for the withdrawal of medication in the treatment of Neither for nor against
Non-Pharmacologic Therapy
We suggest physical therapy for the management of tension-type headache. Weak for
We suggest aerobic exercise or progressive strength training for the management of headache. Weak for
We suggest mindfulness-based therapies for the treatment of headache. Weak for
We suggest education regarding dietary trigger avoidance for the prevention of migraine. Weak for
We suggest non-invasive vagus nerve stimulation for the acute treatment of episodic cluster headache. Weak for
There is insufficient evidence to recommend for or against acupuncture for the treatment of headache. Neither for nor against
There is insufficient evidence to recommend for or against dry needling for the treatment of headache. Neither for nor against
There is insufficient evidence to recommend for or against pulsed radiofrequency or sphenopalatine ganglion block for the treatment of headache. Neither for nor against
There is insufficient evidence to recommend for or against cognitive behavioral therapy or biofeedback for the treatment of headache. Neither for nor against
There is insufficient evidence to recommend for or against an elimination diet based on immunoglobulin G antibody test results for the prevention of headache. Neither for nor against
There is insufficient evidence to recommend for or against the following for headache:
·  Transcranial magnetic stimulation
·  Transcranial direct current stimulation
·  External trigeminal nerve stimulation
·  Supraorbital electrical stimulation
Neither for nor against
Pharmacotherapy
We recommend candesartan or telmisartan for the prevention of episodic or chronic migraine. Strong for
We suggest erenumab, fremanezumab, or galcanezumab for the prevention of episodic or chronic migraine. Weak for
We suggest lisinopril for the prevention of episodic migraine. Weak for
We suggest oral magnesium for the prevention of migraine. Weak for
We suggest topiramate for the prevention of episodic migraine. Weak for
We suggest propranolol for the prevention of migraine. Weak for
We suggest onabotulinumtoxinA injection for the prevention of chronic migraine. Weak for
We suggest against abobotulinumtoxinA or onabotulinumtoxinA injection for the prevention of episodic migraine. Weak against
There is insufficient evidence to recommend for or against gabapentin for the prevention of episodic migraine. Neither for nor against
There is insufficient evidence to recommend for or against nimodipine or nifedipine for the prevention of episodic migraine. Neither for nor against
There is insufficient evidence to recommend for or against coenzyme Q10, feverfew, melatonin, omega-3, vitamin B2, or vitamin B6 for the prevention of migraine. Neither for nor against
There is insufficient evidence to recommend for or against combination pharmacotherapy for the prevention of migraine. Neither for nor against
We recommend sumatriptan (oral or subcutaneous), the combination of sumatriptan/naproxen, or zolmitriptan (oral or intranasal) for the acute treatment of migraine. Strong for
We suggest frovatriptan or rizatriptan for the acute treatment of migraine. Weak for
We suggest triptans instead of opioids or non-opioid analgesics to lower the risk of medication overuse headache for the acute treatment of migraine. Weak for
We suggest ibuprofen, naproxen, aspirin, or acetaminophen for the acute treatment of migraine. Weak for
We suggest greater occipital nerve block for the acute treatment of migraine. Weak for
We suggest intravenous magnesium for the acute treatment of migraine. Weak for
We suggest amitriptyline for the prevention of chronic tension-type headache. Weak for
We suggest against botulinum/neurotoxin injection for the prevention of chronic tension-type headache. Weak against
We suggest ibuprofen (400 mg) or acetaminophen (1,000 mg) for the acute treatment of tension-type headache. Weak for
We suggest galcanezumab for the prevention of episodic cluster headache. Weak for
There is insufficient evidence to recommend for or against any particular medication for the acute treatment of cluster headache. Neither for nor against
There is insufficient evidence to recommend for or against oxygen therapy for the acute treatment of primary headache. Neither for nor against
There is insufficient evidence to recommend for or against valproate for the prevention of headache. Neither for nor against
There is insufficient evidence to recommend for or against fluoxetine or venlafaxine for the prevention of headache. Neither for nor against
We suggest against intravenous ketamine for the acute treatment of headache. Weak against
There is insufficient evidence to recommend for or against intravenous metoclopramide, intravenous prochlorperazine, or intranasal lidocaine for the acute treatment of headache. Neither for nor against
There is insufficient evidence to recommend for or against prescription or non- prescription pharmacologic agents for the treatment of secondary headache. Neither for nor against
a For more information regarding regarding the scope of the CPG, please refer to Scope of this Clinical Practice Guideline in the full text Headache CPG
b For additional information, please refer to Grading Recommendations in the full text Headache CPG
* The category for all recommendations is Reviewed, New-added. For additional information on recommendation categories, please refer to Recommendation Categorization and Appendix B in the full text Headache CPG

Algorithm

Evaluation and Treatment of Headache


Sidebar 1: General History and Physical Exam

Headache history
·  Frequency
·  Character
·  Onset
·  Location
·  Duration
·  Exacerbating factors
·  Relieving factors
·  Prodrome/aura
·  Associated symptoms
·  Jaw symptoms
·  Neck symptoms
·  Visual deficits/changes
·  Dizziness/imbalance
·  Current medications, abortive dose and frequency per month, prophylactic dose
·  Prior medication trials
·  Hydration
·  Meals
·  Caffeine
·  Sleep
·  Exercise
·  Nicotine/stimulant use
·  Other comorbid conditions that may contribute to or exacerbate headaches
·  Risk factors for MOH
·  History of trauma to the head and/or neck
Red flags SNOOP(4)E
·  Systemic symptoms, illness, or condition (e.g., fever, chills, myalgias, night sweats, weight loss or gain, cancer, infection, giant cell arteritis, pregnancy or postpartum, or an immunocompromised state – including HIV)
·  Neurologic symptoms or abnormal signs (e.g., confusion, impaired alertness or consciousness, changes in behavior or personality, diplopia, pulsatile tinnitus, focal neurologic symptoms or signs, meningismus, or seizures ptosis, proptosis, pain with eye movements)
·  Onset (e.g., abrupt or "thunderclap" where pain reaches maximal intensity immediately or within minutes after onset; first ever, severe, or "worst headache of life")
·  Older onset (age ≥50-years)
·  Progression or change pattern (e.g., in attack frequency, severity, or clinical features)
·  Precipitated by Valsalva
(e.g., coughing or bearing down)

·  Postural aggravation
·  Papilledema
·  Exertion
Examination
·  Cranial nerves (including funduscopic exam)
·  Cervical spine and surrounding musculature (palpation, ROM, Spurling’s)
·  Temporomandibular joint (palpation, ROM, symmetry, jaw claudication)
·  Pericranial muscle palpation
·  General neurologic (upper extremities reflexes, sensation, strength, UMN, pathologic reflexes)
·  Temporal artery palpation (tenderness, cord-like artery, or lack of pulse)
·  Blood pressure
Standardized headache assessments:
·  MIDAS
·  HIT-6 
·  MSQL

Sidebar 2: Criteria for Determining Primary Versus Secondary Headache Disorders

Initial evaluation of headache should be targeted at determining if there is a secondary cause for the headache or if the diagnosis of a primary headache disorder is appropriate. Emergent evaluation should be considered based on red flag features. In general, a secondary headache can be diagnosed if the headache is new and occurs in close temporal relation to another disorder that is known to cause headache. It can also be diagnosed when a pre- existing headache disorder significantly worsens in close temporal relation to a causative disorder in which case both the primary and secondary headache diagnoses should be given. ICHD-3 diagnostic criteria are below.

General diagnostic criteria for secondary headaches:
  • Any headache fulfilling C
  • Another disorder scientifically documented to be able to cause headache has been diagnosed. Evidence of causation demonstrated by at least two of the following:
    • Headache has developed in temporal relation to the onset of the presumed causative disorder
    • Either or both of the following: headache has significantly worsened in parallel with worsening of the presumed causative disorder or headache has significantly improved in parallel with improvement of the presumed causative disorder
    • Headache has characteristics typical for the causative disorder
    • Other evidence exists of causation
  • Not better accounted for by another ICHD-3 diagnosis

The secondary headaches include: headache attributed to trauma or injury to the head and/or neck, cranial or cervical vascular disorder, non-vascular intracranial disorder, a substance or its withdrawal, infection, disorder of homeostasis, disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, other facial or cervical structure, or psychiatric disorder
 

Sidebar 3: Primary Headache Disorders Criteria

  Tension-type headachea Migraine headacheb Cluster headachec
Attack duration and frequency Duration 30-minutes – 7-days 4 – 72 hours 15 – 180 minutes
Frequency Variable Variable Once every other day to eight per day; often occurring at the same time of day
Headache characteristics Severity Mild to moderate Moderate to severe Severe or very severe
Location Bilateral Unilateral Unilateral orbital, supraorbital, and/or temporal
Quality Pressing or tightening, non-pulsating Throbbing or pulsating Stabbing, boring
Aggravated by routine physical activity Not aggravated by routine activity Aggravated by routine activity Causes a sense of agitation or restlessness; routine activity may improve symptoms
Associated features Photophobia and phonophobia Can have one but not both Both Variably present
Nausea and/or vomiting Neither Either or both May be present
Other features Autonomic features None May occur, but are often subtle and not noticed by the patient Prominent autonomic features ipsilateral to the pain (see Appendix A in full text Headache CPG)
a A diagnosis of TTH requires at least 10 headache attacks lasting 30-minutes to 7-days with at least two defining characteristics (i.e., bilateral location, non-pulsating quality, mild to moderate intensity, not aggravated by routine physical activity), and both of the associated features (i.e., no nausea or vomiting; either photophobia or phonophobia, but not both). If headaches fulfill all but one of the TTH criteria (e.g., having both photophobia and phonophobia), the diagnosis would be probable TTH.
b A diagnosis of migraine requires at least five attacks lasting 4 – 72 hours with at least two defining headache characteristics (i.e., unilateral, throbbing/pulsating, moderate or severe intensity, aggravated, or caused by routine physical activity) and at least one associated feature (i.e., nausea and/or vomiting and both photophobia and phonophobia). If headaches fulfill all but one of the migraine criteria (e.g., photophobia or phonophobia but not but photophobia and phonophobia), the diagnosis would be probable migraine.
c A diagnosis of cluster headache requires at least five attacks of severe to very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 – 180 minutes and occurring once every other day to no more than eight times a day. Either or both autonomic features and a feeling of restless/agitation are required.
* There are definitions for probable TTH, probable migraine, or probable cluster headache where patients may not fulfill all criteria listed above. The Work Group suggests that providers should not withhold therapy when patients do not meet all criteria listed for TTH, migraine, or cluster headache (i.e., are diagnosed with probable TTH, probable migraine, or probable cluster headache).[7] Providers should continually reassess patients during therapy (see Box 19 in Module A).

Sidebar 4: Treatment Options for Tension-type Headache

Sidebar 4: Treatment Options for Tension-type Headachea, b
Type Treatment Notes
Non-pharmacologic Therapy – Preventive Physical therapy↑ ·  “Physical therapy” refers to a range of interventions carried out by licensed physical therapists, including manual therapy, therapeutic exercise, strength and endurance training, self-management training, and adjunctive modalities
Pharmacotherapy – Preventive Amitriptyline↑ ·  Accessible for general practitioners to prescribe, inexpensive, and may help with patients who suffer from insomnia. Side effects include dry mouth, dry eyes, weight gain, sedation, dizziness, blurred vision, GI distress, and nausea
Botulinum toxin/ neurotoxin↓ ·  Evidence suggests intervention is ineffective for preventing chronic TTH
Pharmacotherapy – Abortive Ibuprofen 400 mg or acetaminophen 1,000 mg↑ ·  Evidence suggests a statistically significant between-group difference for acetaminophen 1,000 mg versus placebo, favoring acetaminophen
a For the full recommendation language, see Recommendations
b Sidebar 8 presents additional treatment options for general headache
Abbreviations: GI: gastrointestinal; mg: milligrams; TTH: tension-type headache
↑ Indicates a “Weak for” recommendation strength; ↓ indicates a “Weak against” recommendation strength

Sidebar 5: Common Medications and their Association with MOH

Sidebar 5: Common Medications and their Association with MOH
MOH Type Medication Overuse Frequency
Acetaminophen overuse ≥15-days/month for >3-months
NSAID overuse
Other non-opioid analgesic overuse
Triptan overuse ≥10-days/month for >3-months
Ergotamine overuse
Opioid overuse ≥10-days/month for >3-months
Combination-analgesic overuse
Abbreviations: MOH: medication overuse headache; NSAID: nonsteroidal anti-inflammatory drug

Sidebar 6: Treatment Options for Migraine Headache

Type Treatment Notes
Pharmacotherapy – Preventive AbobotulinumtoxinA and onabotulinumtoxinA ·  Not FDA approved or effective for prevention of episodic migraine
Candesartan or telmisartan↑↑ ·  Applies to episodic and chronic migraine
Combination pharmacotherapy ·  Evidence was very low quality for the use of combinations of more than one pharmacotherapeutic agent for prevention of migraine
Erenumab, fremanezumab, or galcanezumab ·  Applies to episodic and chronic migraine
·  FDA approved and effective for prevention of migraine
Gabapentin ·  Applies to episodic migraine
·  Not FDA approved or effective for prevention of migraine
Lisinopril ·  Applies to episodic migraine only
Magnesium, oral ·  Oral magnesium formulations varied in the evidence, including magnesium sulfate, magnesium 2-propyl valerate, and magnesium oxide
Nimodipine or nifedipine ·  Applies to episodic migraine only
Nutraceuticals: CoQ10, feverfew, melatonin,
omega-3, vitamin B2, vitamin B6
·  Evidence suggests small but somewhat inconsistent benefits in reducing migraine frequency, which slightly outweighed potential harms, such as dose variability in supplements, and some specific harms, such as post- feverfew syndrome or vitamin B6 neurotoxicity in high, sustained doses
OnabotulinumtoxinA ·  Applies to chronic migraine only
·  FDA approved and effective for prevention of chronic migraine
Propranolol ·  FDA approved for prevention of migraine
Topiramate ·  Applies to episodic migraine only
·  FDA approved and effective for prevention of migraine
Valproate ·  Applies to episodic and chronic migraine
·  FDA approved and effective for prevention of migraine
Pharmacotherapy – Abortive Frovatriptan or rizatriptan ·  FDA approved and effective for treatment of migraine
GON block ·  Evidence suggests improvement of pain intensity
Ibuprofen, naproxen, aspirin, or acetaminophen ·  FDA approved and effective for treatment of migraine
IV magnesium ·  Evidence suggests pain reduction with minimal risks
Sumatriptan, sumatriptan/naproxen, or zolmitriptan↑↑ ·  Sumatriptan alone and in combination with naproxen are FDA approved and effective for prevention of migraine
·  Zolmitriptan is FDA approved and effective for treatment of migraine
Triptans ·  Triptans alone and in combination with naproxen are FDA approved and effective for treatment of migraine
a For the full recommendation language, see Recommendations
bSidebar 8 presents additional treatment options for general headache
Abbreviations: CoQ10: coenzyme Q10; FDA: U.S. Food and Drug Administration; GON: greater occipital nerve block; IV: intravenous
↑↑ Indicates a “Strong for” recommendation strength; ↑ indicates a “Weak for” recommendation strength; ↓ indicates a “Weak against” recommendation strength; ↔ indicates a “Neither for nor against” recommendation strength

Sidebar 7: Treatment Options for Cluster Headache

Sidebar 7: Treatment Options for Cluster Headachea, b
Type Treatment Notes
Non-pharmacologic Therapy – Abortive Non-invasive vagus nerve stimulation ·  For episodic cluster headache only
Pharmacotherapy – Prevention Galcanezumab ·  FDA approved and effective for episodic cluster headache only
Lovastatin# ·  For episodic and chronic cluster headache
Pravastatin# ·  For episodic and chronic cluster headache
Pharmacotherapy – Abortive Oxygen therapy ·  For episodic cluster headache only
Pharmacotherapy for acute treatment ·  Evidence is limited for specific pharmacotherapy for acute treatment of cluster headache
Sumatriptan SQ (not oral)# ·  For episodic and chronic cluster headache
Zolmitriptan nasal spray# ·  FDA approved and effective for episodic and chronic cluster headache
a For the full recommendation language, see Recommendations
b Sidebar 8 presents additional treatment options for general headache
Abbreviations: FDA: U.S. Food and Drug Administration; SQ: subcutaneous
↑ Indicates a “Weak for” recommendation strength; ↔ indicates a “Neither for nor against” recommendation strength; # indicates the treatment was “Not reviewed” in the CPG’s evidence review

Sidebar 8: Treatment Options for Headache in General

Type Treatment Notes
Non-pharmacologic Therapy Acupuncture↔ ·  Evidence suggests small or inconsistent benefits for migraine and TTH in comparison to sham acupuncture
·  No statistically significant differences when compared to beta-blockers, valproic acid, or CCBs, which are also reviewed in this CPG
Aerobic exercise/ progressive strength training ·  Evidence suggests aerobic exercise and progressive strength training decreases headache frequency
CBT or biofeedback ·  Although CBT and biofeedback are commonly used, there was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
Dietary trigger education ·  While the evidence regarding dietary trigger avoidance is limited, it is reasonable to offer patient education regarding diet modification to decrease the frequency and/or severity of their migraine headache
Dry needling ·  Evidence of dry needling compared to no treatment was limited
Elimination-based diet testing ·  There was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
Mindfulness-based therapy ·  Improved outcomes of headache frequency and other potential benefits outweigh the harms with this relatively low-risk activity
Neuromodulation ·  There was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
·  Some patients experienced headache following treatment
Pulsed radiofrequency or SPG ·  There was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
·  Feasibility and acceptability limit these interventions
Pharmacotherapy – Preventive Fluoxetine or venlafaxine↔ ·  There was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
Pharmacotherapy – Abortive IV ketamine↓ ·  Further research should be conducted before administering to patients with headache
IV metoclopramide, IV prochlorperazine, or intranasal lidocaine↔ ·  There was insufficient evidence in this CPG’s systematic evidence review to support a recommendation
a For the full recommendation language, see Recommendations
Abbreviations: CBT: cognitive behavioral therapy; CCB: calcium channel blockers; CPG: Clinical Practice Guideline; IV: intravenous; SPG: sphenopalatine ganglion; TTH: tension-type headache
↑ Indicates a “Weak for” recommendation strength; ↓ indicates a “Weak against” recommendation strength; ↔ indicates a “Neither for nor against” recommendation strength

Table 1. Prevention Dosing Information

Type Drug Initial Dose Usual Range Comments
Beta-adrenic antagonists Atenolol (Tenormin®) 50 mg/day 50 – 200 mg/day ·  Dose should be titrated and maintained for at least three months before assessment of response
Metoprolol (Toprol®, Toprol XL®) 100 mg/day in divided doses 100 – 200 mg/day in divided doses ·  Dose short-acting four times a day and long-acting two times a day
·  Available as extended release
·  Dose should be titrated and maintained for at least three months before assessment of response
Nadolol (Corgard®) 40 – 80 mg/day 80 – 240 mg/day ·  Dose should be titrated and maintained for at least three months before assessment of response
Propranolol (Inderal®, Inderal® LA) 40 mg/day in divided doses 40 – 160 mg/day in divided doses ·  Dose short-acting 2 – 3 times a day and long-acting 1 – 2 times a day
·  Available as extended release
·  Dose should be titrated and maintained for at least three months before assessment of response
Timolol (Blocadren®) 20 mg/day in divided doses 20 – 60 mg/day in divided doses ·  Dose should be titrated and maintained for at least three months before assessment of response
Antidepressants Amitriptyline (Elavil™) 10 mg at bedtime 20 – 50 mg at bedtime ·  Use slow titration to reduce sedation
Venlafaxine (Effexor®, Effexor- XR®) 37.5 mg/day 75 – 150 mg/day ·  Available as extended release
·  Increase dose after one week
Anticonvulsants Topiramate (Topamax®) 25 mg/day 50 – 200 mg/day in divided doses ·  As effective as amitriptyline, propranolol, or valproate
·  Increase by 25 mg/week
Valproic acid/ divalproex sodium (Depakene®, Depakote®, Depakote ER®) 250 – 500 mg/ day in divided doses, or daily for extended release 500 – 1,500 mg/day in divided doses, or daily for extended release ·  Monitor levels if compliance is an issue
Calcitonin Gene-related Peptide Inhibitors Eptinezumab-jjmr (Vyepti) 100 mg IV every 3 months up to 300 mg IV every 3 months ·  May contain polysorbate 80 (also known as Tweens), which can cause hypersensitivity reactions
Erenumab-aooe (Aimovig®) 70 mg SQ monthly 70 – 140 mg SQ monthly ·  May cause constipation, packaging may contain latex
Fremanezumab- vfrm (Ajovy®) 225 mg SQ monthly 225 mg SQ monthly or 675 mg SQ every
3 months
·  May contain polysorbate 80 (also known as Tweens), which can cause hypersensitivity reactions
Galcanezumab- gnlm (Emgality®) 120 mg SQ monthly (migraine), 300 mg SQ (cluster) Can use 240 mg loading dose for migraine, use in cluster should continue monthly until end of cluster period ·  May contain polysorbate 80 (also known as Tweens), which can cause hypersensitivity reactions
Nonsteroidal Anti-inflammatory Drugs Ibuprofen (Motrin®) 400 – 1,200 mg/
day in divided doses
Same as initial dose ·  Use intermittently, such as for menstrual migraine prevention; daily or prolonged use may lead to medication overuse headache and is limited by potential toxicity
Ketoprofen (Orudis®) 150 mg/day in divided doses Same as initial dose ·  Use intermittently, such as for menstrual migraine prevention; daily or prolonged use may lead to medication overuse headache and is limited by potential toxicity
Naproxen sodium (Aleve®, Anaprox®) 550 – 1,100 mg/
day in divided doses
Same as initial dose ·  Use intermittently, such as for menstrual migraine prevention; daily or prolonged use may lead to medication overuse headache and is limited by potential toxicity
Triptans Frovatriptan (Frova®) 2.5 mg/day or 5 mg/day in divided
doses
Same as initial dose ·  Taken in the perimenstrual period to prevent menstrual migraine
Naratriptan (Amerge®) 2 mg/day in divided doses Same as initial dose ·  Taken in the perimenstrual period to prevent menstrual migraine
Zolmitriptan (Zomig®) 5 – 7.5 mg/day in divided doses Same as initial dose ·  Taken in the perimenstrual period to prevent menstrual migraine
Miscellaneous Histamine (Histatrol®) 1 – 10 mg two times/week Same as initial dose ·  May cause transient itching and burning at injection site
Magnesium 400 mg/day 800 mg/day in divided doses ·  May be more helpful in migraine with aura and menstrual migraine
MIG-99 (feverfew) 10 – 100 mg/day in divided doses Same as initial dose ·  Withdrawal may be associated with increased headaches
Petasites 100 – 150 mg/ day in divided doses 150 mg/day in divided doses ·  Use only commercial preparations, plant is carcinogenic
Riboflavin 400 mg/day in divided doses 400 mg/day in divided doses ·  Benefit only after 3 months
Abbreviations: ER: extended release; LA: long acting; mg: milligrams; SQ: subcutaneously; XL: extended release; XR: extended release

Table 2. Abortive Dosing Information

Type Drug Dose Comments
Analgesics Acetaminophen (Tylenol®) 1,000 mg at onset; repeat every 4 – 6 hours as needed ·  Maximum daily dose is 4 g
Acetaminophen 250 mg/aspirin 250 mg/caffeine 65 mg (Excedrin® Migraine) 2 tablets at onset and every 6-hours ·  Available OTC as Excedrin® Migraine
Nonsteroidal Anti- inflammatory Drugs Aspirin 500 – 1,000 mg every 4 – 6 hours ·  Maximum daily dose is 4 g
Diclofenac (Cataflam®, Voltaren®) 50 – 100 mg at onset; can repeat 50 mg in 8-hours ·  Avoid doses >150 mg/day
Ibuprofen (Motrin®) 200 – 800 mg every 6-hours ·  Avoid doses >2.4 g/day
Naproxen sodium (Aleve®, Anaprox®) 550 – 825 mg at onset; can repeat 220 mg in 3 – 4 hours ·  Avoid doses >1.375 g/day
Ergotamine Tartrate Oral tablet (1 mg) with caffeine 100 mg (Cafergot®) 2 mg at onset; then 1 – 2 mg every 30-minutes as needed ·  Maximum dose is 6 mg/day or 10 mg/ week
·  Consider pretreatment with an antiemetic
Sublingual tablet (2 mg) (Ergomar®) 2 mg SL at the first sign of an attack. Then, 2 mg SL after 30 minutes if needed. If the additional dose is well tolerated, the initial dose may be increased at the next attack, up to a maximum initial dose of 4 mg ergotamine. ·  Do not exceed 3 tablets (6 mg ergotamine)/24-hours per any 1 attack
Rectal suppository (2 mg) with caffeine 100 mg (Cafergot®, Migergot®) Insert 1/2 to 1 suppository at onset; repeat after 1-hour as needed ·  Maximum dose is 4 mg/day or 10 mg/ week
·  Consider pretreatment with an antiemetic
Dihydroergotamine Injection 1 mg/mL (D.H.E. 45®) 0.25 – 1 mg at onset IM, IV, or subcutaneous; repeat every hour as needed ·  Maximum dose is 3 mg/day or 6 mg/ week
Nasal spray 4 mg/mL (Migranal®) One spray (0.5 mg) in each nostril at onset; repeat sequence
15-minutes later (total dose is 2 mg or four sprays)
·  Maximum dose is 3 mg/day
·  Prime sprayer four times before using
·  Do not tilt head back or inhale through nose while spraying
·  Discard open ampules after 8-hours
Triptans Zolmitriptan (Zomig®) 5 – 7.5 mg/day in divided doses Same as initial dose ·  Taken in the perimenstrual period to prevent menstrual migraine
Almotriptan (Axert®) 6.25 or 12.5 mg at onset; can repeat after 2-hours if needed ·  Optimal dose is 12.5 mg
·  Maximum daily dose is 25 mg
Eletriptan (Relpax®) 20 or 40 mg at onset; can repeat after 2-hours if needed ·  Maximum single dose is 40 mg
·  Maximum daily dose is 80 mg
Frovatriptan (Frova®) 2.5 or 5 mg at onset; can repeat in 2-hours if needed ·  Optimal dose 2.5 – 5 mg
·  Maximum daily dose is 7.5 mg (three tablets)
Sumatriptan (Imitrex®) injection 6 mg subcutaneous at onset; can repeat after 1-hour if needed ·  Maximum daily dose is 12 mg
Naratriptan (Amerge®) 1 or 2.5 mg at onset; can repeat after 4-hours if needed ·  Optimal dose is 2.5 mg
·  Maximum daily dose is 5 mg
Zolmitriptan nasal spray 5 mg (one spray) at onset; can repeat after 2-hours if needed ·  Maximum daily dose is 10 mg/day
Sumatriptan nasal spray 5, 10, or 20 mg at onset; can repeat after 2-hours if needed ·  Optimal dose is 20 mg
·  Maximum daily dose is 40 mg
·  Single-dose device delivering 5 or 20 mg
·  Administer one spray in one nostril
Zolmitriptan oral tablets 2.5 or 5 mg at onset as regular or orally disintegrating tablet; can repeat after 2-hours if needed ·  Optimal dose is 2.5 mg
·  Maximum dose is 10 mg/day
Sumatriptan oral tablets 25, 50, 85, or 100 mg at onset; can repeat after 2-hours if needed ·  Optimal dose is 50 – 100 mg
·  Maximum daily dose is 200 mg
·  Combination product with naproxen, 85 mg/500 mg
Rizatriptan (Maxalt®, Maxalt-MLT®) 5 or 10 mg at onset as regular or orally disintegrating tablet; can repeat after 2-hours if needed ·  Optimal dose is 10 mg
·  Maximum daily dose is 30 mg
·  Onset of effect is similar with standard and orally disintegrating tablets
·  Use 5 mg dose (15 mg/day maximum) in patients receiving propranolol
Calcitonin Gene Related Peptides Inhibitors Rimegepant (Nurtec™) 75 mg orally disintegrating tablet ·  75 mg per day, doses should not be more frequent than >48-hours
·  Avoid strong CYP3A4 inhibitors, strong or moderate CYP3A4 inducers,
p-glycoprotein inhibitors
Ubrogepant (Ubrelvy®) 50 – 100 mg as a single dose, may repeat in >2-hours ·  Up to 200 mg/24-hours, contraindicated with CYP3A4 inhibitors, dose adjustment in moderate renal impairment and severe (Child Pugh Class C) hepatic impairment
Selective Serotonin 1F Receptor Agonist Lasmidtan (Reyvow™) 50 mg, maximum of one dose per 24-hours ·  50 – 200 mg per 24-hours as a single dose
·  Is a Schedule V drug, may not drive for 8-hours after dose
Miscellaneous Metoclopramide (Reglan®) 10 mg IV at onset ·  Useful for acute relief in the office or ED setting
Prochlorperazine (Compazine®) 10 mg IV or IM at onset ·  Useful for acute relief in the office or ED setting
Abbreviations: CYP3A4: cytochrome P450 3A4; D.H.E.: dihydroergotamine; ED: emergency department; IM: intramuscular; IV: intravenous; mg: milligrams; mL: milliliters; OTC: over-the-counter

Recommendation Grading

Overview

Title

Primary Care Management of Headache

Authoring Organization

Publication Month/Year

July 1, 2020

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory

Scope

Management

Diseases/Conditions (MeSH)

D006261 - Headache, D020773 - Headache Disorders, D014493 - United States Department of Veterans Affairs, D058014 - Veterans Health, D000081324 - Veterans Health Services

Keywords

headache, veteran