What are the appropriate management and treatment options for a patient with a headache?

Management and Treatment of Headache

Initial Assessment: Rule Out Secondary Causes First

Before treating any headache, you must identify red flags that indicate a potentially life-threatening secondary headache requiring immediate neuroimaging or emergency referral. 1

Red flags requiring urgent evaluation include: 1

• Abrupt onset ("thunderclap" headache)
• Headache awakening patient from sleep
• Headache worsened by Valsalva maneuver
• New onset in patients ≥50 years old
• Progressive worsening pattern
• Abnormal neurologic examination findings
• Presence of cancer or immunosuppression
• Provocation by physical activities or postural changes

Neuroimaging is warranted when: 1

• Any unexplained findings on neurologic examination are present
• Red flag symptoms are present (conservative approach)
• Headache has atypical features or doesn't meet strict migraine criteria

If neurologic examination is completely normal and no red flags exist, neuroimaging is usually not warranted and you can proceed with primary headache treatment. 1

Acute Treatment Algorithm for Primary Headache

Step 1: First-Line Treatment for Mild to Moderate Headache

Start with NSAIDs as first-line therapy—they have established efficacy and favorable tolerability. 2, 3

Specific NSAID options with strong evidence: 2

• Ibuprofen 400-800 mg
• Naproxen sodium 500-550 mg
• Aspirin 900-1000 mg
• Combination: acetaminophen + aspirin + caffeine (enhances absorption and provides synergistic analgesia) 2, 3

Critical caveat: Acetaminophen alone is ineffective for migraine and should not be used as monotherapy. 1, 4

Administer as early as possible during the attack to maximize efficacy. 1, 2

Step 2: Escalate to Triptans for Moderate to Severe Headache

If NSAIDs provide inadequate relief within 2 hours, or if the headache is moderate to severe at onset, use triptans as first-line therapy. 2, 5, 3

Triptan options with good evidence: 2, 5

• Oral: sumatriptan, rizatriptan, zolmitriptan, naratriptan
• Subcutaneous sumatriptan 6 mg (highest efficacy: 59% pain-free at 2 hours, but higher adverse events) 2
• Intranasal sumatriptan 5-20 mg (preferred when nausea/vomiting present) 2, 5

Triptans eliminate pain in 20-30% of patients by 2 hours but cause transient flushing, tightness, or tingling in the upper body in 25% of patients. 4

Absolute contraindications to triptans: 5, 3

• Uncontrolled hypertension
• Cardiovascular disease or risk factors
• Basilar or hemiplegic migraine
• Recent use of ergotamines (within 24 hours)

Step 3: Alternative Acute Treatments

For patients who cannot tolerate or have contraindications to triptans, consider: 2, 3

• Gepants (rimegepant or ubrogepant): eliminate headache in 20% at 2 hours, with nausea and dry mouth in 1-4% 4
• Lasmiditan (5-HT1F agonist): safe in patients with cardiovascular risk factors 4
• Intranasal dihydroergotamine (DHE): good evidence for efficacy and safety 2, 5

Step 4: Managing Nausea and Vomiting

Add antiemetics even when nausea is present without vomiting—they provide synergistic analgesia and improve gastric motility. 2, 5, 6

Antiemetic options: 2, 5

• Metoclopramide 10 mg IV/PO (provides both antiemetic and analgesic effects)
• Prochlorperazine 10 mg IV/PO (comparable efficacy to metoclopramide)

When significant nausea/vomiting is present, use non-oral routes (subcutaneous, intranasal, rectal, or IV). 5

Emergency Department/Urgent Care Management

For severe headaches requiring parenteral therapy, use the following combination as first-line: 2

• Ketorolac 30 mg IV (or 60 mg IM if <65 years old) + Metoclopramide 10 mg IV
• This combination provides rapid pain relief with minimal side effects and low risk of rebound headache 2

Alternative IV options: 5, 6

• Prochlorperazine 10 mg IV (comparable to metoclopramide)
• Subcutaneous sumatriptan 6 mg (very rapid onset)
• IV dihydroergotamine 0.5-1.0 mg for refractory cases 5

For status migrainosus (severe continuous migraine lasting up to one week), add IV corticosteroids as mainstay treatment. 3

Avoid opioids—they have questionable efficacy, cause dependency, lead to rebound headaches, and result in loss of efficacy over time. 1, 2, 5, 3

Critical Medication-Overuse Headache Prevention

Limit all acute headache medications to no more than 2 days per week (or 8-10 days per month) to prevent medication-overuse headache. 1, 2, 5, 3

Specific limits: 1

• Simple analgesics (NSAIDs, acetaminophen): <15 days/month
• Triptans: <10 days/month
• Ergotamines, opioids, combination analgesics: <10 days/month

Frequent use of acute medications causes rebound headaches and transformation from episodic to chronic daily headache. 1

When to Initiate Preventive Therapy

Consider preventive therapy when: 3

• ≥2 headaches per week 1
• ≥2 attacks per month producing disability lasting ≥3 days/month 3
• Acute treatments fail or are contraindicated 3
• Abortive medications used more than twice weekly 3

First-line preventive agents: 3

• Propranolol 80-240 mg/day
• Timolol 20-30 mg/day
• Amitriptyline 30-150 mg/day
• Divalproex sodium 500-1500 mg/day

For chronic migraine (≥15 headache days/month), onabotulinumtoxinA is the only FDA-approved preventive therapy and reduces headache days, episodes, severity, and improves quality of life. 1

Important Drug Interactions and Precautions

NSAIDs can: 7

• Reduce effectiveness of ACE-inhibitors and diuretics
• Interfere with antiplatelet effects of aspirin (dose ibuprofen ≥2 hours after aspirin)
• Increase lithium levels and methotrexate toxicity
• Increase bleeding risk with warfarin

Avoid NSAIDs: 7

• After 30 weeks gestation (risk of premature ductus arteriosus closure)
• In patients with history of GI bleeding, renal impairment, or cardiovascular disease
• In aspirin-sensitive asthma (can cause severe bronchospasm)

Follow-Up and Referral

Refer to neurology/headache specialist when: 8

• Cluster headache suspected
• Uncertain diagnosis
• Poor response to preventive strategies
• Migraine with persistent aura
• Headache with associated motor weakness
• Medication-overuse headache on long-term analgesics with unremitting headache

Encourage patients to maintain a headache diary to monitor attack frequency, identify triggers, and assess treatment response. 1