Diagnosis and Management of Headache: A Review

JAMA. 2021 May 11;325(18):1874-1885. doi: 10.1001/jama.2021.1640.


Importance: Approximately 90% of people in the US experience headache during their lifetime. Migraine is the second leading cause of years lived with disability worldwide.

Observations: Primary headache disorders are defined as headaches that are unrelated to an underlying medical condition and are categorized into 4 groups: migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headache disorders. Studies evaluating prevalence in more than 100 000 people reported that tension-type headache affected 38% of the population, while migraine affected 12% and was the most disabling. Secondary headache disorders are defined as headaches due to an underlying medical condition and are classified according to whether they are due to vascular, neoplastic, infectious, or intracranial pressure/volume causes. Patients presenting with headache should be evaluated to determine whether their headache is most likely a primary or a secondary headache disorder. They should be evaluated for symptoms or signs that suggest an urgent medical problem such as an abrupt onset, neurologic signs, age 50 years and older, presence of cancer or immunosuppression, and provocation by physical activities or postural changes. Acute migraine treatment includes acetaminophen, nonsteroidal anti-inflammatory drugs, and combination products that include caffeine. Patients not responsive to these treatments may require migraine-specific treatments including triptans (5-HT1B/D agonists), which eliminate pain in 20% to 30% of patients by 2 hours, but are accompanied by adverse effects such as transient flushing, tightness, or tingling in the upper body in 25% of patients. Patients with or at high risk for cardiovascular disease should avoid triptans because of vasoconstrictive properties. Acute treatments with gepants, antagonists to receptors for the inflammatory neuropeptide calcitonin gene-related peptide, such as rimegepant or ubrogepant, can eliminate headache symptoms for 2 hours in 20% of patients but have adverse effects of nausea and dry mouth in 1% to 4% of patients. A 5-HT1F agonist, lasmiditan, is also available for acute migraine treatment and appears safe in patients with cardiovascular risk factors. Preventive treatments include antihypertensives, antiepileptics, antidepressants, calcitonin gene-related peptide monoclonal antibodies, and onabotulinumtoxinA, which reduce migraine by 1 to 3 days per month relative to placebo.

Conclusions and relevance: Headache disorders affect approximately 90% of people during their lifetime. Among primary headache disorders, migraine is most debilitating and can be treated acutely with analgesics, nonsteroidal anti-inflammatory drugs, triptans, gepants, and lasmiditan.

Publication types

  • Review

MeSH terms

  • Analgesics / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Calcitonin Gene-Related Peptide Receptor Antagonists / therapeutic use
  • Diagnosis, Differential
  • Headache Disorders* / diagnosis
  • Headache Disorders* / etiology
  • Headache Disorders* / therapy
  • Humans
  • Migraine Disorders / diagnosis
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / prevention & control
  • Tension-Type Headache / diagnosis
  • Tension-Type Headache / drug therapy
  • Tryptamines / therapeutic use


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Tryptamines