What is the first-line treatment for Hemicrania Continua (HC) and Paroxysmal Hemicrania (PH)?

First-Line Treatment for Hemicrania Continua and Paroxysmal Hemicrania

Indomethacin is the first-line treatment for both Hemicrania Continua (HC) and Paroxysmal Hemicrania (PH), providing complete and sustained relief of symptoms in most patients. 1, 2

Understanding These Headache Disorders

Hemicrania Continua (HC)

• Continuous, unilateral headache of moderate intensity
• May have superimposed exacerbations of severe pain
• Often accompanied by autonomic features (tearing, nasal congestion, ptosis)
• Absolute response to indomethacin is diagnostic

Paroxysmal Hemicrania (PH)

• Multiple daily attacks of severe, unilateral pain
• Short duration (2-30 minutes)
• Prominent autonomic features
• Absolute response to indomethacin is diagnostic

Treatment Algorithm

First-Line Treatment

• Indomethacin: Start at 25mg three times daily and titrate up as needed
  • Typical effective dose: 75-150mg/day 1
  • Some patients may require higher doses (up to 225mg/day) 3
  • 42% of patients may experience a decrease in required dose (up to 60% reduction) with long-term treatment 1

Gastrointestinal Protection

• Add proton pump inhibitor or H2 blocker (e.g., ranitidine) to prevent GI side effects 1
• Consider enteric-coated formulations

Second-Line Options (for indomethacin intolerance)

For Paroxysmal Hemicrania:

• Verapamil has shown efficacy as a second-line agent 4
• NSAIDs: Acetylsalicylic acid, naproxen, or diclofenac may be partially effective 4

Emerging Treatments

• Noninvasive vagus nerve stimulation has shown promise for both conditions and may be indomethacin-sparing 2

Monitoring and Follow-up

Initial Evaluation

• Brain MRI with pituitary views is recommended at diagnosis 2
• High indomethacin requirements (≥225mg/day) may warrant additional investigation for secondary causes 3

Long-term Management

• Monitor for indomethacin side effects, particularly gastrointestinal
• Attempt dose reduction every 3-6 months to find minimum effective dose
• 23% of patients may experience adverse events, mostly gastrointestinal 1

Important Clinical Pearls

• The response to indomethacin is typically rapid, with relief occurring within 3 days of treatment 1
• The mechanism of indomethacin's unique efficacy may involve inhibition of nitric oxide-induced firing in trigeminovascular neurons 5
• Unlike other NSAIDs, indomethacin specifically inhibits NO-induced firing, which may explain its unique efficacy in these headache disorders 5
• Continuous high indomethacin requirements may occasionally signal an underlying pathology requiring further investigation 3

Differential Diagnosis Considerations

• Other trigeminal autonomic cephalalgias (cluster headache, SUNCT/SUNA)
• Migraine with autonomic features
• Secondary headache disorders (tumors, vascular malformations)

The absolute response to indomethacin is both diagnostic and therapeutic for HC and PH, making proper diagnosis and treatment particularly rewarding for clinicians and life-changing for patients.