What are the alternatives for migraine prevention and treatment without using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Migraine Treatment Without NSAIDs

For acute migraine treatment without NSAIDs, use CGRP antagonists (gepants), triptans, or dihydroergotamine as first-line options depending on severity; for prevention, start with propranolol or timolol as beta-blockers, with topiramate or candesartan as alternatives. 1, 2

Acute Migraine Treatment (Non-NSAID Options)

Mild to Moderate Attacks

• Acetaminophen plus caffeine combination is effective for mild to moderate migraines and should be tried first in this severity category 1
• Isometheptene combinations (such as Midrin) have shown effectiveness for milder migraine headaches 1
• If these fail, escalate to CGRP antagonists or triptans 1

Moderate to Severe Attacks

• CGRP antagonists (gepants) are recommended as first-line alternatives: rimegepant, ubrogepant, or zavegepant 1
• Triptans remain highly effective for moderate to severe attacks, with oral options including sumatriptan, rizatriptan, naratriptan, and zolmitriptan 3
  • Subcutaneous sumatriptan 6mg provides highest efficacy (59% complete pain relief by 2 hours) 3
  • Intranasal formulations (5-20mg) are useful when nausea or vomiting is present 3
  • Important caveat: Triptans require cardiovascular evaluation in patients with multiple cardiac risk factors before first use 4
• Dihydroergotamine (DHE) intranasal formulation has good evidence for efficacy and safety 1
• Lasmiditan (Ditan) is considered when other options are contraindicated or ineffective 1

Adjunctive Therapy for Nausea

• Metoclopramide (10mg IV/oral) provides synergistic analgesia beyond just treating nausea 3
• Prochlorperazine (10mg IV/oral) effectively relieves headache pain and is comparable to metoclopramide 3
• These antiemetics should not be restricted only to patients who are vomiting, as nausea itself warrants treatment 3

Emergency/IV Treatment Protocol

• First-line IV combination: Metoclopramide 10mg IV plus ketorolac 30mg IV provides rapid relief 3
  • Since you cannot use NSAIDs, substitute with: Metoclopramide 10mg IV plus prochlorperazine 10mg IV, or use DHE 3
• Dihydroergotamine IV is an alternative for severe attacks requiring parenteral treatment 3

Critical Medications to Avoid

• Avoid opioids and butalbital-containing medications for routine migraine treatment as they lead to dependency, rebound headaches, and eventual loss of efficacy 1, 3
• Limit acute therapy to no more than twice per week to prevent medication-overuse headache 3, 4

Migraine Prevention (Non-NSAID Options)

Indications for Starting Prevention

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 2
• Using abortive medication more than twice per week 2
• Contraindications to or failure of acute treatments 2
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 2

First-Line Preventive Medications

Beta-Blockers (Strongest Evidence)

• Propranolol 80-240 mg/day has the strongest evidence and is FDA-approved 2
• Timolol 20-30 mg/day is also first-line with strong evidence 2
• Alternative beta-blockers: atenolol, bisoprolol, or metoprolol 2
• Contraindications: Asthma, congestive heart failure, abnormal cardiac rhythms 5
• Common side effects: Dizziness and fatigue 5

Topiramate

• Dose: 100 mg/day (typically 50mg twice daily) 2
• Efficacy demonstrated with 46% of patients achieving ≥50% reduction in migraine frequency 6
• Common adverse effects: Paresthesias, language disorders, confusion, gastrointestinal disturbances, fatigue, anorexia 6, 7
• Most adverse events are mild to moderate and transient 7
• Efficacy can be seen as early as the first month, but allow 2-3 months for full evaluation 2, 7

Candesartan

• Particularly useful for patients with comorbid hypertension 2
• First-line agent with good evidence 2

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day is particularly effective in patients with mixed migraine and tension-type headache 2
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 2, 8
  • Strictly contraindicated in women of childbearing potential due to teratogenic effects 2
• Flunarizine is effective where available 2

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, galcanezumab, or eptinezumab should be considered when first- and second-line options have failed or are contraindicated 2
• Require 3-6 months to assess efficacy (longer than oral agents) 2

Implementation Strategy

• Start low, titrate slowly until clinical benefits are achieved or side effects limit further increases 2
• Adequate trial period: 2-3 months for oral agents before determining efficacy 2
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 2
• After 6-12 months of successful therapy, consider pausing preventive treatment to determine if it can be discontinued 2

Non-Pharmacological Adjuncts

• Neuromodulatory devices can be used as adjuncts or stand-alone treatments when medications are contraindicated 2
• Biobehavioral therapy and acupuncture can be considered as adjuncts 2

Common Pitfalls to Avoid

• Medication-overuse headache: Results from using acute medications ≥15 days/month (or ≥10 days/month with triptans) 1, 4
• Inadequate trial duration: Failing to give preventive medications 2-3 months (or 3-6 months for CGRP antibodies) before declaring failure 2
• Starting preventive dose too high: Leads to poor tolerability and discontinuation 2
• Not addressing cardiovascular risk before prescribing triptans in high-risk patients 4
• Using opioids routinely: Creates dependency and worsens headache patterns 1, 3