What are the recommended outpatient treatment options for acute headache with no red flags?

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Last updated: November 6, 2025View editorial policy

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Outpatient Treatment for Acute Headache Without Red Flags

For moderate to severe acute headache without red flags, add a triptan to an NSAID (such as naproxen 500 mg with sumatriptan 50-100 mg) if the patient has already tried an NSAID alone without adequate relief. 1

Initial Assessment and Treatment Strategy

First-Line Approach for Mild to Moderate Headache

  • Start with an NSAID monotherapy: ibuprofen 400-600 mg, naproxen 500 mg, diclofenac potassium, or aspirin 500-1000 mg 1, 2
  • If NSAIDs are contraindicated or not tolerated, use acetaminophen 1000 mg 1
  • For mild episodic headache, consider the combination of an NSAID plus acetaminophen 1

Escalation for Moderate to Severe Headache

The American College of Physicians strongly recommends combination therapy as the most effective approach: 1

  • Triptan + NSAID combination (e.g., sumatriptan 50-100 mg + naproxen 500 mg) provides the greatest net benefit with moderate-certainty evidence 1

    • This combination achieves pain relief at 2 hours in 90 more patients per 1000 compared to triptan alone 1
    • Sustained pain relief at 48 hours occurs in 130 more patients per 1000 versus triptan monotherapy 1
    • Reduces rescue medication use by 130 fewer events per 1000 patients at 24 hours 1
  • Triptan + acetaminophen combination (e.g., rizatriptan + acetaminophen 1000 mg) is recommended when NSAIDs are contraindicated, though with lower-certainty evidence 1

Specific Triptan Options

Available triptans include almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan 1

  • If one triptan fails, try another within the same class as patients may respond differently 1, 2
  • Choose based on route of administration preference and cost 1
  • Sumatriptan tablets achieve headache response (reduction to mild or no pain) in 52-62% of patients at 2 hours versus 17-27% with placebo 3

Timing and Administration

  • Begin treatment as soon as possible after headache onset to maximize efficacy 1, 4
  • For severe nausea or vomiting, use a non-oral triptan formulation with an antiemetic 1, 2

Second-Line Options for Treatment Failures

If combination therapy of triptan + NSAID or acetaminophen fails or is not tolerated: 1

  • Consider CGRP antagonists-gepants (rimegepant, ubrogepant, or zavegepant) 1
  • Consider ergot alkaloid dihydroergotamine 1
  • Lasmiditan (ditan) may be used if all other treatments fail 1

Critical Contraindications and Warnings

Medications to Avoid

Do not use opioids or butalbital for acute headache treatment due to dependency risk, rebound headaches, and eventual loss of efficacy 1, 2

Triptan Contraindications

Triptans are contraindicated in patients with: 3

  • Coronary artery disease or history of myocardial infarction
  • Prinzmetal's angina or coronary artery vasospasm
  • Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
  • History of stroke or transient ischemic attack
  • Peripheral vascular disease
  • Uncontrolled hypertension
  • Hemiplegic or basilar migraine

Cardiovascular Risk Assessment

For triptan-naive patients with multiple cardiovascular risk factors (increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), perform cardiovascular evaluation before prescribing 3

Medication Overuse Headache Prevention

Be aware of medication overuse headache thresholds: 1, 2

  • NSAIDs: ≥15 days per month
  • Triptans: ≥10 days per month
  • Defined as headache occurring ≥15 days per month for at least 3 months in patients with preexisting headache disorder 1

If frequent episodic headaches occur or acute treatment provides inadequate response, consider adding preventive medications 1

Lifestyle Modifications

Counsel patients on non-pharmacologic interventions: 1, 4, 2

  • Maintain adequate hydration and regular meals
  • Ensure sufficient and consistent sleep (7-9 hours)
  • Engage in regular moderate to intense aerobic exercise
  • Practice stress management with relaxation techniques or mindfulness
  • Pursue weight loss if overweight or obese
  • Identify and avoid personal headache triggers through detailed history

Cost Considerations

  • Prescribe less costly recommended medications when possible 1
  • CGRP antagonists-gepants have significantly higher costs (annualized wholesale acquisition cost $4,959-$8,800) compared to triptans and NSAIDs 1
  • Generic formulations of triptans and NSAIDs provide cost-effective options 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment of Acute, Non-Emergent Headache in Clinic

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Migraine Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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