What are migraine headaches, including their assessment, pharmacology, and pathophysiology?

Migraine Headaches: Assessment, Pharmacology, and Pathophysiology

Migraine headaches are recurrent episodes of moderate to severe headache characterized by pulsating pain lasting 4-72 hours, often accompanied by nausea, vomiting, photophobia, and phonophobia, which significantly impact quality of life and require a combination of a triptan with an NSAID for optimal treatment of moderate to severe attacks. 1

Pathophysiology

Migraine is a neurovascular disorder with complex underlying mechanisms:

• Neuronal Hyperexcitability: Migraine brains show increased excitability, with genetic variants affecting glutamate neurotransmission and synaptic plasticity 2
• Cortical Spreading Depression (CSD): A wave of neuronal depolarization that may trigger migraine attacks, particularly those with aura 3
• Trigeminovascular Activation: The primary mechanism of headache pain, involving:
  • Activation of trigeminal nerve pathways
  • Release of calcitonin gene-related peptide (CGRP)
  • Neurogenic inflammation
  • Pain transmission to central pathways 3, 2
• Brainstem Involvement: PET studies show activation of a "migraine generator" region in the brainstem during attacks 3
• Genetic Factors: Multiple genes contribute to migraine susceptibility, with stronger hereditary patterns in migraine with aura 2

Assessment

Diagnostic Criteria (International Headache Society) 1

Migraine without aura requires:

• At least 5 attacks with:
  • Duration 4-72 hours (untreated or unsuccessfully treated)
  • At least two of: unilateral location, pulsating quality, moderate/severe intensity, aggravation by routine physical activity
  • At least one of: nausea/vomiting, photophobia and phonophobia

Migraine with aura includes:

• Visual, sensory, speech/language, motor, brainstem, or retinal symptoms
• Aura symptoms developing gradually over 5+ minutes
• Each aura symptom lasting 5-60 minutes

Red Flags Requiring Further Investigation 4

• Headache worsened with Valsalva maneuver
• Headache awakening patient from sleep
• New-onset headache in older patients
• Progressively worsening headache pattern
• Neurological symptoms or abnormal exam
• Headache during sexual activity

Assessment Tools

• Headache Diary: Document frequency, severity, triggers, and medication use 4
• Disability Assessment: Evaluate impact on daily activities and quality of life 1

Pharmacological Management

Acute Treatment

1. First-Line for Mild to Moderate Attacks 1, 4, 5:

   • Simple analgesics: acetaminophen, NSAIDs (ibuprofen, naproxen)
   • Take at onset of headache for best results

2. First-Line for Moderate to Severe Attacks 1, 4, 5:

   • Add a triptan to an NSAID (strong recommendation, moderate-certainty evidence)
     • Examples: sumatriptan + naproxen
   • Add a triptan to acetaminophen (conditional recommendation, low-certainty evidence)

3. Second-Line Options 4, 5:

   • CGRP antagonists (gepants): rimegepant, ubrogepant, zavegepant
   • 5-HT1F agonists (ditans): lasmiditan
   • Dihydroergotamine (ergot alkaloid)
   • Antiemetics for significant nausea/vomiting

4. Not Recommended 4:

   • Opioids and butalbital-containing medications (high risk of medication overuse headache)

Medication Overuse Prevention 4

• Limit triptans to ≤10 days/month
• Limit NSAIDs to ≤15 days/month

Preventive Treatment

Consider preventive therapy when 1, 4:

• Migraine occurs ≥2 times per month
• Attacks are prolonged and disabling
• Poor response to acute treatments
• Quality of life is reduced between attacks

First-Line Preventive Options 1, 4:

• Beta-blockers: propranolol (80-240 mg/day), timolol (20-30 mg/day)
• Antiseizure medications: topiramate (100 mg/day), valproate (500-1500 mg/day)
• Tricyclic antidepressants: amitriptyline (30-150 mg/day)
• Angiotensin receptor blockers: candesartan, telmisartan
• CGRP antagonists or monoclonal antibodies

Target Goal: 50% reduction in attack frequency 4

Non-Pharmacological Management

Trigger Identification and Avoidance 1, 4

Common triggers include:

• Stress and stress letdown
• Hormonal changes
• Sleep disturbances
• Certain foods and beverages
• Environmental factors (bright lights, strong odors)
• Weather changes

Lifestyle Modifications 4

• Maintain regular sleep schedule
• Stay well hydrated
• Regular physical activity
• Stress management techniques
• Cognitive behavioral therapy

Supplements with Evidence 4

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

Special Considerations

Pregnancy and Lactation 4

• Acetaminophen is safest acute option
• Avoid valproate and topiramate (teratogenic)
• Women with migraine with aura should avoid combined hormonal contraceptives

Cardiovascular Risk 4

• Use triptans with caution in elderly patients
• Consider lower initial doses in high-risk patients

Comorbidities 4

• Monitor blood glucose when initiating preventive medications in diabetic patients
• Weight management may improve migraine frequency and severity

Common Pitfalls and Caveats

1. Underdiagnosis and Undertreatment: Migraine remains underdiagnosed and undertreated, affecting approximately 16% of the US population (21% of females, 11% of males) 1

2. Medication Overuse: Excessive use of acute medications can lead to medication overuse headache, worsening the migraine cycle 4

3. Delayed Treatment: Early administration of medication improves efficacy; patients should be instructed to take medication at headache onset 4

4. Inadequate Dosing: Using subtherapeutic doses of medications reduces effectiveness 5

5. Failure to Consider Prevention: Patients with frequent or disabling migraines should be evaluated for preventive therapy 1, 4

6. Ignoring Comorbidities: Depression, anxiety, and sleep disorders often coexist with migraine and require appropriate management 4