What is the best pharmacotherapy for headaches?

Best Pharmacotherapy for Headaches

For acute treatment of headaches, first-line therapy should be stratified based on headache severity: simple analgesics (acetaminophen, NSAIDs) for mild to moderate migraine, and triptans for moderate to severe attacks. 1

Acute Treatment Algorithm

Mild to Moderate Migraine Headaches

1. First-line options:

   • Acetaminophen 1000 mg (provides headache relief in 56% of patients at 2 hours) 2
   • NSAIDs:
     • Ibuprofen 400 mg (provides headache relief in 57% of patients at 2 hours) 3
     • Naproxen sodium
   • Consider soluble formulations for faster relief 3

2. Second-line options (if first-line fails):

   • Combination therapy: Acetaminophen 1000 mg plus metoclopramide 10 mg 2
   • Triptans (e.g., zolmitriptan) 4

Moderate to Severe Migraine Headaches

1. First-line options:

   • Triptans:
     • Zolmitriptan (provides headache relief in 59-67% of patients at 2 hours) 4
     • Other triptans (sumatriptan, rizatriptan, etc.)

2. Second-line options:

   • Gepants (rimegepant, ubrogepant) - especially for patients with cardiovascular contraindications to triptans 5
   • Ditans (lasmiditan) - safe in patients with cardiovascular risk factors 5
   • Antiemetics with analgesics 1
   • Ergot alkaloids 1

Preventive Treatment for Recurrent Headaches

For patients with frequent headaches requiring prevention:

1. First-line preventive medications:

   • Beta-blockers:
     • Propranolol (80-240 mg/day)
     • Timolol (20-30 mg/day)
   • Antidepressants:
     • Amitriptyline (30-150 mg/day)
   • Anticonvulsants:
     • Topiramate (100 mg/day)
     • Divalproex sodium (500-1500 mg/day)
   • Angiotensin receptor blockers:
     • Candesartan (8-32 mg daily) 6

2. Second-line preventive options:

   • Flunarizine (calcium channel blocker)
   • Venlafaxine (75-150 mg daily) 6

3. Supplements with evidence for prevention:

   • Magnesium (400-600 mg daily)
   • Riboflavin (400 mg daily)
   • Coenzyme Q10 6

Important Clinical Considerations

• Evaluate response to preventive treatment after 6-8 weeks, with a goal of 50% reduction in headache frequency 6
• Avoid opioids and butalbital-containing medications unless other options have been ineffective 1
• Special populations:
  • Women with migraine with aura should avoid combined hormonal contraceptives due to increased stroke risk
  • Use topiramate and valproate with caution in women of childbearing potential due to teratogenic effects 6

Treatment Pitfalls to Avoid

• Medication overuse headache: Limit acute medications to ≤10 days per month for triptans/ergots and ≤15 days for simple analgesics
• Cardiovascular contraindications: Avoid triptans and ergot alkaloids in patients with coronary artery disease, uncontrolled hypertension, or stroke history 5
• Delayed treatment: Early intervention during migraine attacks leads to better outcomes
• Inadequate dosing: Using suboptimal doses reduces effectiveness (e.g., ibuprofen 400 mg is more effective than 200 mg) 3

Monitoring and Follow-up

• Monitor for medication efficacy and adverse effects
• Consider specialist referral if two or more preventive medication trials fail, diagnosis uncertainty exists, or complex comorbidities are present 6
• Implement lifestyle modifications alongside pharmacotherapy: regular sleep schedule, meals, moderate exercise, stress management, and adequate hydration 6