What injection treatments are available for a patient with severe and recurrent migraine headaches, considering their medical history and potential cardiovascular disease?

Injectable Treatments for Severe and Recurrent Migraine Headaches

For Chronic Migraine (≥15 headache days/month)

OnabotulinumtoxinA (Botox) injections are the recommended first-line injectable treatment for chronic migraine, reducing headache days by approximately 1.8 days per month with a favorable safety profile. 1

OnabotulinumtoxinA Protocol

• Dosing: 155-195 units injected across 31-39 sites every 12 weeks following the PREEMPT protocol 1, 2
• Efficacy timeline: Requires 2-3 treatment cycles (6-9 months) to assess full response 3
• Response criteria: Define as responder if ≥30% reduction in headache days per month, though also consider headache intensity, disability, and patient preferences 2
• Discontinuation: Stop treatment if <30% response after 2-3 cycles, or if headache days reduce to <10 days/month for 3 consecutive months 2
• Important caveat: Do NOT use onabotulinumtoxinA or abobotulinumtoxinA for episodic migraine (<15 headache days/month), as adverse events favor placebo over treatment 1

CGRP Monoclonal Antibodies (Subcutaneous)

For patients with episodic or chronic migraine, CGRP monoclonal antibodies provide strong preventive efficacy with excellent tolerability. 1

• Erenumab, fremanezumab, or galcanezumab: Strong recommendation for both episodic and chronic migraine prevention 1
• Fremanezumab dosing: 225 mg monthly OR 675 mg quarterly subcutaneous 4
• Galcanezumab dosing: 240 mg loading dose, then 120 mg monthly subcutaneous 5
• Efficacy: Reduces monthly migraine days by 3.4-4.7 days compared to baseline 4, 5
• Cardiovascular safety: Studies excluded patients with significant cardiovascular disease, stroke, MI, unstable angina, or thrombotic events within 6 months 4, 5
• Time to efficacy: Assess response after 3-6 months of treatment 3

Intravenous Eptinezumab

• Indication: Prevention of episodic or chronic migraine when subcutaneous options are unsuitable 1
• Dosing: 300 mg IV infusion provides optimal efficacy 1
• Practical limitation: Requires healthcare center infrastructure for IV administration and significant time commitment from patient 1
• Recommendation strength: Weak for, as benefits slightly outweigh harms and burdens 1

For Acute Severe Migraine Attacks (Injectable Abortive Treatment)

Subcutaneous Sumatriptan

Subcutaneous sumatriptan 6 mg is the most effective and rapidly acting injectable medication for acute migraine, providing pain relief in 70-82% of patients within 15 minutes. 1, 3, 6

• Dosing: 6 mg subcutaneous at migraine onset, maximum 2 doses in 24 hours 3
• Peak concentration: Achieved in approximately 15 minutes 3
• Complete pain relief: 59% of patients by 2 hours 3
• Contraindications: Ischemic heart disease, previous MI, uncontrolled hypertension, significant cardiovascular disease 3, 6

IV Combination Therapy for Emergency/Urgent Care

For severe migraine requiring IV treatment, metoclopramide 10 mg IV plus ketorolac 30 mg IV provides the most effective combination with minimal rebound headache risk. 3, 6

• Metoclopramide 10 mg IV: Provides direct analgesic effects through central dopamine receptor antagonism, independent of antiemetic properties 3, 6
• Ketorolac 30 mg IV: Rapid onset with approximately 6 hours duration, minimal rebound headache risk 3, 6
• Alternative IV option: Dihydroergotamine (DHE) has good evidence for efficacy as monotherapy 3
• Avoid: IV ketamine (weak against recommendation) and opioids (lead to dependency, rebound headaches, loss of efficacy) 1, 3, 6

Critical Considerations for Cardiovascular Disease

Contraindications with Cardiovascular History

• Triptans (including subcutaneous sumatriptan): Contraindicated in ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 3, 6
• CGRP monoclonal antibodies: Clinical trials excluded patients with recent (within 6 months) stroke, MI, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, deep vein thrombosis, or pulmonary embolism 4, 5
• OnabotulinumtoxinA: Studies excluded patients with significant cardiovascular disease, vascular ischemia, or thrombotic events 4

Safe Injectable Options with Cardiovascular Disease

• Ketorolac 30 mg IV: Use with caution in heart disease, but not absolutely contraindicated 3
• Metoclopramide 10 mg IV: No specific cardiovascular contraindications, though contraindicated in pheochromocytoma 3
• Consider: Greater occipital nerve block has insufficient evidence for chronic migraine prevention, but may be considered when other options are contraindicated 1

Medication Overuse Headache Prevention

Strictly limit all acute injectable medications to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily chronic headaches. 3, 6

• High-risk factors: Headache frequency ≥7 days/month, frequent use of analgesics or anxiolytics, history of anxiety/depression, physical inactivity 1
• Transition strategy: If requiring acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing acute medication frequency 3, 6