What are the treatment options for migraines?

Migraine Treatment: Comprehensive Management Guide

Acute Treatment Algorithm

For acute episodic migraine, start with NSAIDs or acetaminophen for mild-to-moderate attacks; escalate to combination therapy (triptan + NSAID or acetaminophen) for moderate-to-severe attacks or when monotherapy fails. 1

First-Line: NSAIDs and Acetaminophen

• NSAIDs are the initial treatment for mild-to-moderate migraine attacks, with proven efficacy for aspirin, ibuprofen, naproxen sodium, and diclofenac potassium 2, 3
• Aspirin-acetaminophen-caffeine combination is highly effective, with a number needed to treat (NNT) of 4 for pain relief at 2 hours 2
• Acetaminophen alone has less efficacy than NSAIDs and should be reserved for patients intolerant of NSAIDs 2
• Administer treatment as early as possible during the attack, ideally when pain is still mild, to prevent central sensitization 1, 2
• Naproxen dosing: 500-825 mg at onset, repeatable every 2-6 hours (maximum 1.5 g/day), limited to 3 consecutive days 3

Second-Line: Triptan Monotherapy or Combination Therapy

If NSAIDs or acetaminophen at adequate doses provide insufficient relief, add a triptan to create combination therapy rather than switching to triptan monotherapy. 1

• Combination therapy of triptan (sumatriptan or rizatriptan) + NSAID (naproxen) or acetaminophen has greater net benefit than triptan monotherapy 1
• All oral triptans (sumatriptan, rizatriptan, zolmitriptan, naratriptan, almotriptan, frovatriptan, eletriptan) are effective for moderate-to-severe attacks 2, 4
• If one triptan fails, try another - failure of one triptan does not predict failure of others 2, 3
• Triptans are most effective when taken early while headache is still mild 2

Route selection for triptans:

• Oral tablets: standard first choice for most patients 2
• Subcutaneous sumatriptan 6 mg: highest efficacy (59% pain-free at 2 hours) and fastest onset (15 minutes), ideal for severe attacks or when vomiting precludes oral administration 3, 5
• Intranasal sumatriptan or zolmitriptan: rapid absorption with pain-free rates as early as 15 minutes, useful when nausea/vomiting present 2, 5
• Orally disintegrating tablets (rizatriptan, zolmitriptan): for patients with difficulty swallowing or who prefer not to use liquids 5

Third-Line: Advanced Options

For patients who fail all available triptans or have contraindications, use CGRP antagonists (gepants: rimegepant, ubrogepant, zavegepant), lasmiditan, or dihydroergotamine. 1, 2

• Ubrogepant and rimegepant: NNT of 13 for pain freedom at 2 hours 2
• Lasmiditan: robust benefit but significant adverse effects including driving restrictions (NNH of 4 for treatment-emergent adverse effects) 2
• Dihydroergotamine (DHE): good evidence for efficacy, particularly intranasal formulation 3

Managing Associated Symptoms

• Add antiemetics (metoclopramide 10 mg IV or prochlorperazine 10 mg IV) for nausea/vomiting - these provide synergistic analgesia beyond just treating nausea 2, 3
• Use non-oral routes (subcutaneous, intranasal, rectal, IV) when significant nausea or vomiting is present 2, 3
• Metoclopramide enhances gastric motility and improves absorption of co-administered oral medications 3

Critical Medication Overuse Prevention

Limit acute medication use to prevent medication overuse headache: ≤10 days/month for triptans, ≤15 days/month for NSAIDs. 2, 4

• Using acute medications more than twice weekly leads to increasing headache frequency and potentially daily headaches 2, 3
• Avoid opioids and butalbital-containing analgesics - they cause dependency, rebound headaches, and loss of efficacy 2, 3

IV Treatment for Severe Migraine in Urgent Care/Emergency Settings

The optimal IV migraine cocktail is ketorolac 30 mg IV + metoclopramide 10 mg IV, providing rapid pain relief with minimal rebound risk. 3

• Ketorolac: 30 mg IV (or 60 mg IM if <65 years old), rapid onset with 6-hour duration 3
• Metoclopramide 10 mg IV: provides direct analgesic effects through dopamine receptor antagonism plus treats nausea 3
• Prochlorperazine 10 mg IV: comparable efficacy to metoclopramide, may have fewer extrapyramidal side effects 3
• Avoid prednisone/corticosteroids for routine acute migraine - limited evidence; reserve for status migrainosus 3
• Never use hydromorphone or other opioids except as absolute last resort when all other options contraindicated and abuse risk addressed 3

Preventive Therapy Indications

Initiate preventive therapy when patients have ≥2 attacks per month producing disability lasting ≥3 days, use acute medications >2 days/week, or have inadequate response to acute treatments. 2

First-Line Preventive Medications

• Propranolol 80-240 mg/day or timolol 20-30 mg/day: beta-blockers with strongest evidence 3
• Topiramate: effective but requires discussion of teratogenic effects with patients of childbearing potential 2
• Amitriptyline 30-150 mg/day: particularly useful for mixed migraine and tension-type headache 3
• Divalproex sodium/sodium valproate: effective but has adverse events including weight gain, hair loss, tremor, and teratogenic potential 3

Second-Line Options

• ACE inhibitors or ARBs: consider if first-line agents not tolerated 2
• SSRIs: alternative when other options fail 2
• Start preventive medications at low dose and gradually titrate until desired outcomes achieved 2

Chronic Migraine (≥15 Headache Days/Month)

OnabotulinumtoxinA 155 units is FDA-approved and specifically effective for chronic migraine based on large-scale trials. 2

• Rule out secondary causes before establishing chronic migraine diagnosis 2
• Monitor closely for medication overuse headache 2
• Efficacy timeline: 6-9 months for onabotulinumtoxinA, 3-6 months for CGRP monoclonal antibodies, 2-3 months for oral agents 3

Non-Pharmacologic and Behavioral Treatments

Cognitive-behavioral therapy, biofeedback, and relaxation training should be offered to all patients as part of comprehensive management. 2

• Regular moderate-to-intense aerobic exercise (40 minutes, 3 times weekly) is as effective as some preventive medications 2
• Stress management with relaxation techniques or mindfulness practices 2
• Maintain regular meals, adequate hydration, and sufficient consistent sleep 2
• Use headache diary to identify triggers, monitor treatment efficacy, and detect analgesic overuse 2

Important Safety Considerations and Contraindications

Triptan Contraindications and Warnings

• Contraindicated in uncontrolled hypertension, ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, and peripheral vascular disease 6, 7
• Can cause coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular arrhythmias, and death 6, 7
• Evaluate patients with chest, jaw, or neck tightness after sumatriptan for CAD or Prinzmetal angina before giving additional doses 6
• Risk of serotonin syndrome when combined with SSRIs or SNRIs - requires careful observation during initiation and dose increases 6, 7
• May cause significant blood pressure elevation including hypertensive crisis 6, 7
• Contraindicated with MAO-A inhibitors - sumatriptan levels increase 7-fold orally, nearly double subcutaneously 6, 7

Cerebrovascular and Other Vasospastic Events

• Cerebral hemorrhage, subarachnoid hemorrhage, stroke reported with triptans 6, 7
• Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported 6, 7
• Rare reports of transient and permanent blindness and significant partial vision loss 6, 7
• Exclude other serious neurological conditions before treating atypical headaches - some reported cases were not migraine but other conditions 6, 7

NSAID Precautions

• Use caution in renal impairment (creatinine clearance <30 mL/min), history of GI bleeding, aspirin/NSAID-induced asthma 3
• Ketorolac contraindicated in active GI bleeding and severe renal impairment 3

Antiemetic Precautions

• Metoclopramide contraindicated in pheochromocytoma, seizure disorder, GI bleeding, and GI obstruction 3
• Prochlorperazine: risk of tardive dyskinesia, hypotension, tachycardia, arrhythmias; contraindicated in CNS depression and with adrenergic blockers 3
• Limit use to no more than twice weekly to prevent medication overuse headache 3

Clinical Pitfalls to Avoid

• Do not allow patients to increase acute medication frequency when treatment fails - this creates medication overuse headache; instead transition to preventive therapy 3
• Do not use opioids routinely - reserve only when all other options contraindicated, sedation acceptable, and abuse risk addressed 3
• Do not assume all severe headaches are migraine - exclude secondary causes, especially with atypical features or first severe headache 6, 7
• Do not give ergotamine-containing drugs within 24 hours of triptans - theoretical risk of additive vasospastic effects 6
• Do not exceed maximum daily acetaminophen dose of 4000 mg from all sources when using combination products 3