What treatment options are available for a patient with chronic headaches unresponsive to steroids or over-the-counter (OTC) medication, considering their demographic and past medical history?

Treatment for Headache Unresponsive to Steroids or OTC Medications

For headaches that have failed both steroids and over-the-counter medications, add a triptan to an NSAID as the next step for moderate to severe headaches, or consider preventive therapy if attacks occur more than twice per week. 1

Immediate Next Steps for Acute Treatment

First: Rule Out Medication Overuse Headache

• Before escalating therapy, assess for medication overuse headache, which occurs with regular use of acute medications on ≥10 days/month for triptans or ≥10 days/month for any combination of acute medications for ≥3 months. 1
• Medication overuse can cause treatment resistance and must be addressed before other interventions will be effective. 1
• If medication overuse is present, a short course of oral corticosteroids (prednisone or dexamethasone) can be used during the detoxification process to manage withdrawal symptoms. 2

Second: Escalate to Triptan-NSAID Combination

• The American College of Physicians strongly recommends adding a triptan to an NSAID for moderate to severe headaches that don't respond adequately to NSAIDs alone. 1
• Effective triptan options include oral sumatriptan, rizatriptan, naratriptan, or zolmitriptan, taken early in the attack when headache is still mild. 3
• 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
• Critical contraindication: Avoid triptans in patients with cardiovascular disease or risk factors due to vasoconstrictive properties. 5, 4

Third: Alternative Acute Therapies if Triptans Fail or Are Contraindicated

• If all triptans fail or are contraindicated, consider gepants (ubrogepant, rimegepant) or ditans (lasmiditan). 3
• Gepants eliminate headache in 20% of patients at 2 hours with adverse effects of nausea and dry mouth in 1-4% of patients. 4
• Lasmiditan (a 5-HT1F agonist) is safe in patients with cardiovascular risk factors, unlike triptans. 4
• For rapid-onset severe headaches, subcutaneous sumatriptan can be used when oral triptans have failed. 3, 5

Transition to Preventive Therapy

Indications for Starting Prevention

Preventive therapy should be initiated if any of the following apply:

• Attacks occur ≥2 times per month with disability lasting ≥3 days per month. 6
• Using acute medications more than 2 days per week (to prevent medication overuse headache). 1, 7
• Contraindications to or failure of multiple acute treatments. 6
• Uncommon migraine conditions such as hemiplegic migraine or migraine with prolonged aura. 6

First-Line Preventive Medications

Start with one of these evidence-based first-line agents:

• Propranolol 80-240 mg/day (strong evidence, FDA-approved). 6
• Topiramate 50-100 mg/day (particularly useful in patients with obesity due to weight loss effects). 6
• Candesartan (especially useful for patients with comorbid hypertension). 6

Implementation Strategy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases. 6
• Allow an adequate trial period of 2-3 months before determining efficacy. 6
• Track attack frequency, severity, duration, and disability using headache diaries. 6

Second-Line Preventive Medications

If first-line agents fail or are not tolerated:

• Amitriptyline 30-150 mg/day (optimal for patients with comorbid depression or anxiety). 6
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day (strictly contraindicated in women of childbearing potential due to teratogenic effects). 6
• Flunarizine 5-10 mg once daily at night (effective second-line agent where available, but avoid in elderly due to risk of extrapyramidal symptoms and depression). 6

Third-Line: CGRP Monoclonal Antibodies

For patients who have failed 2-3 oral preventive medications:

• Consider erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection. 6
• Efficacy assessment requires 3-6 months (longer than oral agents). 6
• These agents reduce migraine by 1-3 days per month relative to placebo but cost $5,000-$6,000 annually. 6, 4

Critical Red Flags Requiring Neuroimaging

Obtain MRI or CT immediately if any of these features are present:

• Sudden "thunderclap" onset of headache. 7
• Fever or unexplained systemic symptoms. 7
• Headache worsened by Valsalva maneuver or exercise. 7
• Abnormal neurologic examination. 7
• Rapidly increasing frequency or severity. 7
• New onset in patient over age 50. 7
• Headache that awakens patient from sleep. 1

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache, which interferes with all other treatments and requires detoxification first. 6
• Inadequate duration of preventive trial (less than 2-3 months for oral agents, less than 3-6 months for CGRP antibodies). 6
• Starting preventive medications at too high a dose, leading to poor tolerability and discontinuation. 6
• Using triptans in patients with cardiovascular disease or risk factors (hypertension, high cholesterol, diabetes, smoking, family history of heart disease, postmenopausal women, males over 40). 5
• Not limiting acute medication use to ≤2 days per week, which perpetuates medication overuse headache. 7

Non-Pharmacological Adjuncts

Consider adding these evidence-based non-pharmacological interventions:

• Cognitive behavioral therapy, biofeedback, and relaxation training alongside medication. 6
• Trigger identification and modification: sleep hygiene, regular meals, hydration, stress management. 6
• Neuromodulatory devices as adjuncts when medications are contraindicated. 6