
Am Fam Physician. 2021;104(2):316-320
Author disclosure: No relevant financial affiliations.
Key Points for Practice
• Ibuprofen and high-dose acetaminophen improve acute tension-type headaches. Amitriptyline is effective at preventing tension-type headaches after three months of treatment.
• Triptans, ibuprofen, naproxen, aspirin, and high-dose acetaminophen are effective treatments for acute migraine. Intravenous magnesium and greater occipital nerve blocks are also effective.
• Effective migraine preventive medications include candesartan, telmisartan, lisinopril, oral magnesium, topiramate, propranolol, erenumab, fremanezumab, and galcanezumab.
• Galcanezumab reduces cluster headache frequency, whereas triptans and oxygen may improve acute cluster headaches.
From the AFP Editors
Headache disorders affect two-thirds of people in their lifetime, and a large number of potential treatments exist. The U.S. Department of Veterans Affairs and U.S. Department of Defense (VA/DoD) published updated guidelines for the treatment of headache disorders based on a systematic review.
Secondary Headaches
Secondary headaches are caused by an identifiable process. Cervicogenic headache, posttraumatic headache, and medication overuse headache are the most common secondary headaches. Red flag symptoms (Table 1) suggest a secondary headache etiology requiring urgent investigation. Primary headaches are diagnosed when a secondary cause cannot be identified (Figure 1).

Systemic symptoms, illness, or condition (e.g., cancer, chills, fever, immunocompromise, infection, myalgias, night sweats, pregnancy or postpartum, weight loss) |
Neurologic symptoms or abnormal signs (e.g., confusion, diplopia, focal neurologic signs, impaired consciousness, meningismus, pulsatile tinnitus, seizures) |
Onset occurs with maximal intensity within minutes or “thunderclap” headache |
Older (age ≥ 50 years at onset) |
Progression (e.g., change in features, pattern, severity) |
Precipitated by Valsalva |
Postural aggravation |
Papilledema |
Exertional provocation |

Medication overuse headaches result from frequent use of acute headache medications. Medication overuse headaches often have a frequency between seven and 14 days per month and usually start after three months of frequent acute medication use. Using anxiolytics, analgesics, and sleep-inducing medications increases medication overuse headache risk. Celecoxib (Celebrex), prednisone, and specific medication withdrawal strategies have been proposed to wean overused medications, but none are superior to usual care.
Some nonpharmacologic treatments are effective for most headaches. Aerobic exercise and progressive strength training decrease headache frequency for numerous headache disorders. Mindfulness-based therapies may slightly reduce headache frequency for all headache types. Acupuncture yields small or inconsistent pain relief compared with sham acupuncture. Cognitive behavior therapy and biofeedback do not seem to be effective. Dietary food elimination trials and neuromodulation, including transcranial magnetic stimulation, transcranial direct current stimulation or pulsed radiofrequency, and sphenopalatine ganglion block have insufficient evidence.
There is no proven preventive medication for secondary headaches. Small studies suggest fluoxetine (Prozac) and venlafaxine slightly improve uncharacterized episodic headaches.
Primary Headaches
Tension-type, migraine, and cluster headaches are the most common primary headaches. Primary headaches are differentiated by clinical criteria from the International Classification of Headache Disorders, third edition. Episodic headaches occur fewer than 15 days a month, whereas chronic headaches occur more frequently. Although criteria help distinguish primary headaches, therapy should not be withheld if criteria are not fully met. Instead, empiric therapy for a probable headache diagnosis should be considered (Table 2).

Headache subtype | Diagnostic criteria | Nonpharmacologic treatment options | Pharmacologic treatment options |
---|---|---|---|
Tension-type | ≥ 10 headaches lasting 30 minutes to 7 days plus two of the following: Mild to moderate severity Squeezing, tightening quality Bilateral/global symptoms Typically not associated with nausea, vomiting, or autonomic symptoms | Physical therapy | Acute relief: Acetaminophen, ibuprofen Preventive: Amitriptyline |
Migraine | Episodic: < 15 headache days in 30 days Chronic: ≥ 15 headache days in 30 days ≥ 5 headaches lasting 4 to 72 hours plus two of the following: Moderate to severe intensity Unilateral symptoms Throbbing, pulsating quality Nausea, photophobia, and/or phonophobia Aggravated by activity | Dietary trigger avoidance | Acute relief: Nonsteroidal anti-inflammatory drugs Triptans (frovatriptan [Frova], rizatriptan [Maxalt], sumatriptan [Imitrex], naproxen/sumatriptan [Treximet], zolmitriptan [Zomig] Preventive: Angiotensin-converting enzyme inhibitor (lisinopril) Angiotensin receptor blocker (candesartan [Atacand], telmisartan [Micardis]) Calcitonin gene-related peptide receptor inhibitors (erenumab [Aimovig], fremanezumab [Ajovy], galcanezumab [Emgality]) Magnesium (oral) OnabotulinumtoxinA (Botox; only for chronic migraine [> 15 days per month]) Propranolol Topiramate (Topamax) |
Cluster | ≥ 5 severe or very severe orbital or temporal headaches lasting 15 to 180 minutes and recurring every other day to 8 times per day plus either: Ipsilateral autonomic features or Restlessness/agitation | Preventive: Noninvasive vagus nerve stimulation | Preventive: Galcanezumab |
General headache | Includes primary and secondary headache disorders | Aerobic exercise and progressive strength training Mindfulness-based therapy | Pharmacologic options are based on subtype |
Tension-Type Headaches
Tension-type headaches affect more than one-half of adults and last from 30 minutes to seven days. They present with at least two of the following characteristics: bilateral location, a squeezing or tightening sensation, mild to moderate intensity, and no change with physical activity. Nausea and vomiting are not present. Photophobia or phonophobia may be present, but normally not both.
Physical therapy, specifically manual therapy, modestly reduces tension-type headache frequency. Other nonpharmacologic treatments are not effective.
For acute medical treatment, only acetaminophen and ibuprofen have been studied. Acetaminophen at 1,000 mg and ibuprofen at 400 mg increase the likelihood of being pain free two hours later; lower doses of acetaminophen are not effective.
Amitriptyline effectively prevents tension-type headaches, reducing headache frequency and the need for abortive medications. Benefits are seen after three months of use. OnabotulinumtoxinA (Botox) injections are not effective for tension-type headaches.
Migraine Headaches
Migraines last from four hours to three days and have at least two defining characteristics of unilaterality, moderate to severe intensity, throbbing or pulsating sensation, and aggravation by regular activity. Nausea, vomiting, photophobia, and phonophobia are commonly present.
Avoiding dietary triggers decreases migraine frequency, so education about these triggers can be helpful. Limited study suggests noninvasive vagus nerve stimulation is not beneficial. Greater occipital nerve blocks are effective for acute migraines without significant adverse effects.
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