What are the treatment options for a patient experiencing migraines?

Migraine Treatment

Acute Treatment Algorithm

For mild-to-moderate migraine attacks, start with NSAIDs (aspirin, ibuprofen, naproxen) or aspirin-acetaminophen-caffeine combination; escalate to triptans for moderate-to-severe attacks or when NSAIDs fail within 2 hours. 1, 2

First-Line Acute Treatment (Mild-to-Moderate Attacks)

• NSAIDs with proven efficacy include aspirin, ibuprofen, naproxen sodium, and diclofenac potassium as initial therapy. 3, 2
• The aspirin-acetaminophen-caffeine combination is highly effective, with a number needed to treat of 9 for pain freedom at 2 hours and 4 for pain relief at 2 hours. 2
• Acetaminophen alone is ineffective and should only be used in patients intolerant of NSAIDs. 3, 2
• Begin treatment as soon as possible after migraine onset to maximize efficacy. 2

Second-Line Acute Treatment (Moderate-to-Severe Attacks or NSAID Failure)

• Triptans should be offered when over-the-counter analgesics provide inadequate relief within 2 hours. 1, 2
• Triptans are most effective when taken early while headache is still mild. 2
• Oral triptans with proven efficacy include naratriptan, rizatriptan, zolmitriptan, and sumatriptan (25-100 mg doses all superior to placebo, with 50-100 mg showing better response rates than 25 mg). 3, 4
• Combining a triptan with an NSAID or acetaminophen improves efficacy beyond either agent alone. 2
• If one triptan fails, trial a different triptan as response varies between agents. 2
• Contraindications to triptans include uncontrolled hypertension, basilar or hemiplegic migraine, and cardiovascular disease risk. 3
• Subcutaneous sumatriptan is useful for patients with severe vomiting who cannot tolerate oral medications. 2

Third-Line Acute Treatment (Triptan Failures or Contraindications)

• CGRP antagonists (gepants) including rimegepant, ubrogepant, or zavegepant are options for triptan failures, though with a higher number needed to treat of 13 for pain freedom. 2
• Lasmiditan (ditan) demonstrates robust benefit but has significant adverse effects including driving restrictions (number needed to harm of 4). 2
• Dihydroergotamine (DHE) has good evidence for efficacy and safety when administered intranasally. 3

Managing Associated Symptoms

• Use non-oral routes of administration (nasal spray, subcutaneous injection, suppository) when nausea or vomiting are prominent early symptoms. 3, 2
• Treat nausea with antiemetics such as metoclopramide or prochlorperazine, which also improve gastric motility and enhance absorption of oral medications. 2

Critical Medication Overuse Prevention

• Limit NSAIDs to fewer than 15 days per month and triptans to fewer than 10 days per month to prevent medication overuse headache. 2
• Limit acute treatment use to no more than twice weekly to guard against medication-overuse headaches. 3
• Avoid opioids and butalbital-containing analgesics due to risk of dependency, rebound headaches, and questionable efficacy. 3, 2

Preventive Therapy Indications

Initiate preventive therapy when patients experience ≥2 attacks per month producing disability lasting ≥3 days per month, use acute medications more than twice weekly, have contraindications to acute treatments, or suffer from uncommon migraine variants (hemiplegic migraine, prolonged aura, migrainous infarction). 3, 1, 2

First-Line Preventive Medications

• Beta-blockers (propranolol, metoprolol, atenolol, bisoprolol) are first-line agents, particularly beneficial in patients with comorbid hypertension. 1, 2
• Topiramate (50-100 mg daily) is first-line for episodic migraine and the only oral medication proven effective in randomized placebo-controlled trials specifically for chronic migraine (≥15 headache days per month), especially beneficial in obese patients. 1, 2
• Amitriptyline is first-line with documented high efficacy, particularly useful for patients with coexisting depression or anxiety. 1, 2
• Candesartan (angiotensin receptor blocker) is first-line, particularly useful in hypertensive patients. 2
• Start preventive medications at low doses and gradually titrate upward until desired outcomes are achieved or side effects limit further increases. 2
• Topiramate requires discussion of teratogenic effects with patients of childbearing potential before initiation. 2

Second-Line Preventive Medications

• Consider ACE inhibitors, ARBs, or SSRIs if first-line treatments are not tolerated or result in inadequate response. 2

Third-Line Preventive Medications (Refractory Cases)

• CGRP monoclonal antibodies (erenumab 70-140 mg subcutaneous monthly, fremanezumab 225 mg monthly or 675 mg quarterly, galcanezumab, eptinezumab 100-300 mg intravenous quarterly) for patients who have failed first- and second-line agents. 1, 2
• OnabotulinumtoxinA 155 units every 12 weeks is FDA-approved specifically for chronic migraine (≥15 headache days per month) based on large-scale, double-blind, placebo-controlled trials. 1, 2

Preventive Treatment Assessment and Duration

• Assess efficacy of oral preventive medications after 2-3 months at therapeutic dose. 2
• For CGRP monoclonal antibodies, assess efficacy after 3-6 months; for onabotulinumtoxinA, assess after 6-9 months. 5
• Consider pausing preventive treatment after 6-12 months of successful control to determine if therapy can be stopped. 2
• Switch preventive treatment if adequate response is not achieved during a reasonable trial period. 1, 2

Non-Pharmacologic Treatments

• Cognitive-behavioral therapy, biofeedback, and relaxation training have good evidence for efficacy and should be integrated into comprehensive management. 1, 2
• Regular moderate-to-intense aerobic exercise for 40 minutes three times weekly is as effective as topiramate or relaxation therapy for migraine prevention. 1, 2
• Maintain regular meals, adequate hydration, and sufficient sleep as foundational lifestyle modifications. 2
• Manage stress with relaxation techniques or mindfulness practices. 2

Monitoring and Comorbidity Management

• Monitor treatment efficacy using headache diaries to track severity, frequency, duration of attacks, degree of disability, response to treatment, adverse medication effects, and identify migraine triggers (alcohol, caffeine, tyramine-containing foods, stress, fatigue, perfumes, flickering lights). 3, 1
• Treat comorbid conditions with medications that also benefit migraine when possible, such as amitriptyline for depression and migraine, or beta-blockers for hypertension and migraine. 1
• Use validated disability tools such as the Migraine Disability Assessment Score and HIT-6 to track treatment response. 5

Common Pitfalls to Avoid

• Do not abandon preventive treatment prematurely—efficacy takes weeks to months to establish. 5
• Avoid oral ergot alkaloids, opioids, and barbiturates due to questionable efficacy with considerable adverse effects and dependency risk. 2, 5
• Failure of one preventive treatment does not predict failure of other drug classes—trial alternative agents if initial preventive fails. 5
• Consider the possibility of rebound headaches associated with withdrawal of analgesic drugs or abortive migraine medications, particularly with opiates, triptans, ergotamine, and analgesics containing caffeine, isometheptene, or butalbital. 3