Migraine Treatment in Adults

For acute episodic migraine, start with NSAIDs (ibuprofen 400–800 mg or naproxen 500–825 mg) at the first sign of headache; escalate to sumatriptan 50–100 mg plus naproxen 500 mg for moderate-to-severe attacks or after NSAID failure in 2–3 episodes. 1, 2, 3

Acute Treatment Algorithm

Step 1: First-Line Therapy for Mild-to-Moderate Attacks

Initiate an NSAID immediately when pain is still mild: ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg. 1, 3
Early treatment (while pain is mild) achieves pain-free response at 2 hours in ~50% of patients versus ~28% when delayed until pain is moderate-to-severe. 1, 3
Acetaminophen 1000 mg is an alternative when NSAIDs are contraindicated, though less effective. 1, 3

Step 2: Escalation to Combination Therapy

For moderate-to-severe attacks or after NSAID failure in 2–3 episodes, give sumatriptan 50–100 mg PLUS naproxen sodium 500 mg. 1, 3
This combination provides 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared with sumatriptan alone, with a number-needed-to-treat of 3.5 for 2-hour headache relief. 1, 3
The combination is superior to either agent alone and represents the strongest-rated acute intervention. 1, 3

Step 3: Alternative Triptans if Sumatriptan Fails

Try a different triptan (rizatriptan 10 mg, eletriptan 40 mg, or zolmitriptan 2.5–5 mg) because failure of one triptan does not predict failure of others. 2
Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes, particularly useful for rapid progression or significant nausea/vomiting. 2
Intranasal sumatriptan 5–20 mg is effective when oral routes are impaired by nausea. 2

Step 4: CGRP Antagonists (Gepants) for Triptan-Intolerant Patients

Ubrogepant 50–100 mg or rimegepant are third-line options when triptans are contraindicated or after failure of triptan-NSAID combinations. 1, 3
Gepants have no vasoconstriction and are safe in cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease. 2, 3
Limit ubrogepant to no more than 8 migraine attacks per 30-day period. 2

Step 5: Parenteral Options for Severe Attacks

Intravenous metoclopramide 10 mg plus ketorolac 30 mg is the recommended first-line IV combination for severe migraine requiring emergency treatment. 2
Metoclopramide provides direct analgesic effects through central dopamine antagonism, not just antiemetic benefit. 2
Ketorolac has rapid onset, approximately 6-hour duration, and minimal rebound headache risk. 2
Dihydroergotamine (DHE) 0.5–1.0 mg IV is an alternative monotherapy with good evidence for efficacy. 2, 3

Critical Frequency Limitation: Preventing Medication-Overuse Headache

Limit ALL acute migraine medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 3
This threshold applies to NSAIDs, triptans, gepants, combination analgesics, and all other acute agents. 1, 3
If acute medication use exceeds 2 days per week, initiate preventive therapy immediately. 1, 3

Contraindicated Acute Medications

Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) are absolutely contraindicated because they provide questionable efficacy, carry high dependence risk, precipitate rebound headaches, and worsen long-term outcomes. 1, 2, 3
Butalbital-containing compounds should never be used for the same reasons. 1, 2, 3

Preventive Therapy

Indications for Starting Preventive Treatment

≥2 migraine attacks per month with disability lasting ≥3 days, OR 1, 4, 3
Acute medication use >2 days per week, OR 1, 4, 3
Failure, contraindication, or intolerable side effects of acute treatments, OR 1, 4, 3
Patient preference for prevention. 1, 3

First-Line Oral Preventive Medications

When treatments have comparable net benefit, cost should guide selection, favoring less expensive options first. 1

Beta-Blockers (Strongest Traditional Evidence)

Propranolol 80–240 mg/day has the most robust evidence among traditional preventives, with FDA approval and multiple randomized controlled trials. 1, 4, 3
Doses below 160 mg/day are generally sub-therapeutic; maximum recommended dose is 240 mg/day. 4
Timolol 20–30 mg/day also has strong evidence. 1, 4, 3
Alternative beta-blockers include metoprolol, atenolol, nadolol, and bisoprolol. 1, 4
Contraindications: asthma, heart block, severe peripheral vascular disease. 4

Topiramate (Strongest Evidence for Chronic Migraine)

Topiramate 50–100 mg/day (typically 50 mg twice daily) is the only oral preventive with robust RCT evidence specifically for chronic migraine. 1, 4, 3
Preferred when obesity is present because it promotes weight loss. 4
Common adverse effects include cognitive impairment, paresthesias, and weight loss. 1

Amitriptyline (Second-Line but Evidence-Based)

Amitriptyline 30–150 mg/day is preferred for patients with comorbid depression, anxiety, sleep disturbance, or mixed migraine/tension-type headache. 1, 4, 3
Lacks robust RCT evidence specifically for chronic migraine; efficacy is mainly demonstrated in episodic migraine. 4

Divalproex/Valproate (Second-Line with Important Safety Caveat)

Divalproex sodium 500–1500 mg/day or sodium valproate 800–1500 mg/day are effective. 1, 4, 3
Strictly contraindicated in women of childbearing potential due to teratogenic risk. 1, 4, 3
Common adverse effects include weight gain, hair loss, and tremor. 1, 4

Second-Line Oral Options (Limited Evidence)

Lisinopril (ACE inhibitor), candesartan or telmisartan (ARBs), and fluoxetine (SSRI) have limited evidence from small studies but may be considered when first-line agents fail. 1
Flunarizine 5–10 mg once daily (where available) is effective as a second-line agent but should be avoided in patients with Parkinsonism or depression. 4

Third-Line Options for Refractory/Chronic Migraine

CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, galcanezumab) should be considered when two or more oral preventives have failed or are contraindicated. 1, 4, 3
Assess efficacy after 3–6 months of therapy. 1, 4, 3
OnabotulinumtoxinA (Botox) 155–195 U across 31–39 injection sites every 12 weeks is the only FDA-approved preventive specifically for chronic migraine (≥15 headache days/month). 2, 4, 3
Evaluate onabotulinumtoxinA efficacy after 6–9 months. 2, 4, 3

Preventive Therapy Principles

Start low, titrate slowly to the effective dose or until intolerable side effects appear. 1, 3
Adequate trial periods: oral agents 2–3 months; CGRP monoclonal antibodies 3–6 months; onabotulinumtoxinA 6–9 months. 1, 4, 3
Switch agents if response is inadequate after a reasonable trial or if adverse events occur. 1, 3
Use a headache diary (paper or electronic) to track attack frequency, medication use, and treatment response. 1, 4, 3
Discuss pregnancy-related risks before initiating any preventive medication; avoid teratogenic agents in women of childbearing potential. 1, 3

Non-Pharmacologic Adjuncts

Behavioral therapies (cognitive-behavioral therapy, relaxation training, mindfulness-based treatment, biofeedback) can reduce migraine frequency and disability. 1, 3
Lifestyle modifications: identify and mitigate triggers such as sleep deprivation, stress, dehydration, irregular physical activity, tobacco, and alcohol. 1, 4, 3

Common Pitfalls to Avoid

Do not maintain sub-therapeutic doses (e.g., propranolol <160 mg or amitriptyline <30 mg) indefinitely; optimize doses before declaring treatment failure. 4
Do not abandon treatment prematurely; oral preventives require 2–3 months at target dose before efficacy can be judged. 1, 4, 3
Do not allow patients to increase acute medication frequency in response to treatment failure; this creates a vicious cycle of medication-overuse headache. 2
Do not prescribe opioids or butalbital compounds for migraine under any routine circumstances. 1, 2, 3

What is the recommended acute and preventive treatment for an adult with episodic migraine?

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