What is the best treatment approach for a patient with headache syndrome, considering preventive medication, lifestyle modifications, and alternative therapies?

Treatment of Headache Syndrome

For patients with migraine-type headache syndrome, initiate acute treatment with combination therapy of a triptan plus an NSAID or acetaminophen, and strongly consider preventive medication (propranolol, topiramate, or candesartan) if headaches occur ≥2 days per month with significant disability. 1, 2

Initial Assessment and Classification

The critical first step is determining whether the headache is primary (migraine, tension-type, cluster) or secondary to an underlying condition. Look specifically for red-flag features including: 3, 4

• Thunderclap onset (sudden, severe, "worst headache of life") suggesting subarachnoid hemorrhage 5, 4
• Age >50 years with new-onset headache requiring ESR/CRP to exclude temporal arteritis 6, 5
• Neurologic deficits on examination mandating immediate neuroimaging 5, 3
• Headache worsening with Valsalva or positional changes suggesting increased intracranial pressure 4
• Morning headaches resolving within hours suggesting obstructive sleep apnea 6

If any red flags are present, obtain urgent neuroimaging (MRI preferred over CT) and appropriate laboratory studies before initiating treatment. 6, 5

Acute Treatment Strategy

First-Line Acute Treatment

For moderate to severe migraine attacks, combination therapy is superior to monotherapy and should be initiated as soon as possible after headache onset: 1

• Triptan (sumatriptan 50-100 mg, rizatriptan, or eletriptan) PLUS NSAID (ibuprofen 400-800 mg or naproxen 500-1000 mg) or acetaminophen 1
• Add an antiemetic with prokinetic properties (metoclopramide) if nausea is prominent 1
• Triptans eliminate pain at 2 hours in 20-30% of patients but cause transient flushing, tightness, or tingling in 25% 7, 3

Critical contraindications for triptans include: uncontrolled hypertension, coronary artery disease, Prinzmetal's angina, stroke/TIA history, hemiplegic or basilar migraine, and Wolff-Parkinson-White syndrome 1, 7

For Mild Migraine

Start with NSAID monotherapy (ibuprofen, naproxen, or aspirin) or the combination of acetaminophen-aspirin-caffeine. 1 Acetaminophen alone is ineffective for migraine. 1

Second-Line Acute Options

If triptans fail or are contraindicated, consider CGRP antagonists (gepants: rimegepant 75 mg, ubrogepant 50-100 mg, or zavegepant nasal spray). 1 These eliminate headache at 2 hours in approximately 20% of patients with adverse effects of nausea and dry mouth in 1-4%. 3

Lasmiditan (5-HT1F agonist) is reserved for patients who fail all other treatments and is safe in those with cardiovascular risk factors, unlike triptans. 1, 3

Critical Medication Overuse Warning

Never use opioids or butalbital-containing compounds for migraine treatment. 1 These medications lead to medication overuse headache (MOH) and worsen the overall headache burden. 1, 7

Limit acute medication use to prevent MOH: 1

• Triptans: ≤10 days per month
• NSAIDs: ≤15 days per month
• Any acute medication: avoid use >2 days per week

Preventive Treatment Strategy

Indications for Preventive Therapy

Initiate preventive treatment if any of the following apply: 2

• Headaches occurring ≥2 days per month causing disability for ≥3 days per month 1, 2
• Using acute medications >2 days per week or approaching medication overuse thresholds 1, 2
• Failure of or contraindications to acute treatments 1, 2
• Patient preference to reduce attack frequency 1

First-Line Preventive Medications

Choose from these evidence-based first-line agents: 1, 2

• Propranolol 80-240 mg/day (or alternative beta-blockers: metoprolol, atenolol, bisoprolol, timolol 20-30 mg/day) 1, 2
• Topiramate 50-100 mg/day (particularly beneficial in patients with obesity due to weight loss effects) 1, 2
• Candesartan 16 mg/day (especially useful with comorbid hypertension) 1, 2

Start at low doses and titrate slowly over 2-3 months to assess efficacy and tolerability. 2 An adequate trial requires 2-3 months before determining effectiveness. 1, 2

Second-Line Preventive Medications

If first-line agents fail or are not tolerated: 1, 2

• Amitriptyline 30-150 mg/day (optimal for comorbid depression, anxiety, or mixed migraine/tension-type headache) 1, 2
• Flunarizine 5-10 mg/day at night (effective but monitor for sedation, weight gain, depression, and extrapyramidal symptoms; avoid in elderly and those with Parkinson's disease) 2
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day (STRICTLY CONTRAINDICATED in women of childbearing potential due to teratogenic effects) 1, 2

Third-Line: CGRP Monoclonal Antibodies

Consider CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, or eptinezumab) only after failure of 2-3 oral preventive medications. 1, 2 These require subcutaneous injection monthly and cost $5,000-6,000 annually. 2 Allow 3-6 months to assess efficacy. 2

Lifestyle Modifications and Non-Pharmacological Approaches

Implement these evidence-based lifestyle strategies alongside medication: 1

• Sleep hygiene: consistent sleep schedule with 7-8 hours nightly 1
• Regular meals and hydration: avoid skipping meals, limit caffeine intake 1
• Regular aerobic exercise: moderate to intense physical activity 1
• Stress management: cognitive-behavioral therapy, biofeedback, mindfulness, or relaxation training 1, 2
• Trigger identification and avoidance: use headache diaries to track patterns 2

Consider neuromodulatory devices or acupuncture as adjuncts when medications are contraindicated, though evidence for physical therapy and dietary approaches is limited. 1, 2

Management of Medication Overuse Headache

If MOH is present (headache ≥15 days/month for ≥3 months with overuse of acute medications): 1

• Abruptly stop non-opioid analgesics and triptans (or taper within 1 month) 1
• Gradually withdraw opioids over ≥1 month if present 1
• Initiate preventive therapy early as MOH prevents effectiveness of preventive treatments 1
• Expect transient worsening of headache during withdrawal 1

Headache-Specific Considerations

For IIH-Associated Headache

Tailor treatment to the headache phenotype (68% have migrainous features). 1 Use migraine-specific therapies as above, with these additions: 1

• Short-term NSAIDs or acetaminophen in first weeks (indomethacin may have advantage due to ICP-lowering effects) 1
• Avoid opioids completely 1
• Acetazolamide treats papilledema but NOT headache alone 1
• Lumbar punctures are not recommended for headache treatment 1

For Tension-Type Headache

Acute treatment: NSAIDs 8 Preventive treatment: Tricyclic antidepressants (amitriptyline) 8

For Cluster Headache and Trigeminal Autonomic Cephalalgias

Acute treatment requires specific approaches beyond standard migraine therapy (high-flow oxygen, subcutaneous sumatriptan). 8 Indomethacin is often effective for paroxysmal hemicrania. 8

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache before starting preventive therapy 2
• Inadequate trial duration (<2-3 months) before declaring preventive treatment ineffective 2
• Starting preventive medications at too high a dose leading to poor tolerability and discontinuation 2
• Using triptans in patients with cardiovascular disease or risk factors without proper evaluation 7
• Prescribing valproate to women of childbearing potential 1, 2
• Missing secondary headache causes in patients >50 years with new-onset headache 6, 5

Duration and Reassessment

After 6-12 months of successful preventive therapy, consider tapering to determine if treatment can be discontinued. 2 Use headache diaries to calculate percentage reduction in monthly migraine days as a measure of success. 2