Migraine Without Aura

Migraine without aura is a recurrent headache disorder manifesting as attacks lasting 4 to 72 hours, typically unilateral, pulsating, moderate to severe in intensity, aggravated by routine physical activity, and associated with nausea and/or photophobia and phonophobia, in the absence of a reversible neurological aura.

• Diagnostic criteria: at least 5 attacks; attack duration 4 to 72 hours (untreated or unsuccessfully treated); at least two of unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or avoidance of routine physical activity; at least one of nausea and/or vomiting, or photophobia and phonophobia.
• Accounts for about 75 to 80 percent of migraine; lifetime prevalence about 15 to 20 percent in adults, and about 3 times more common in women.
• Attacks have four possible phases: prodrome (yawning, mood change, food craving, neck stiffness), headache, resolution, and postdrome.
• Common triggers: sleep disturbance, missed meals, stress and relaxation after stress, menstruation, alcohol (red wine), bright light, strong smells, weather change, and certain foods.
• Chronic migraine: headache on 15 or more days a month for over 3 months, with at least 8 days having migraine features.
• Comorbidity: depression, anxiety, hypertension, epilepsy, irritable bowel syndrome, and a small increased risk of ischaemic stroke and cardiovascular disease, especially in migraine with aura.

• Headache: unilateral (but can be bilateral), throbbing, building over minutes to hours, worse with movement; patients prefer to lie still in a dark, quiet room.
• Associated: nausea, vomiting, photophobia, phonophobia, osmophobia, neck stiffness, cutaneous allodynia, lightheadedness, and fatigue.
• Duration 4 to 72 hours; in children 2 to 72 hours, often bilateral.
• Examination between attacks is normal; check blood pressure, fundi, neck, temporal arteries, and a focused neurological examination.
• Red flags (SNNOOP10): systemic symptoms including fever; neoplasm history; neurological deficit or altered consciousness; onset sudden or thunderclap; older age (new headache after 50); pattern change or recent onset; positional headache; precipitated by Valsalva, cough or exertion; papilloedema; progressive headache or atypical presentations; pregnancy or puerperium; painful eye with autonomic features; post-traumatic onset; pathology of the immune system such as HIV; painkiller overuse or new drug exposure.

• Clinical. No investigation is needed when features are typical and examination is normal.
• Headache diary for at least 4 weeks (days, severity, triggers, medicines, menstrual relationship).
• Neuroimaging (MRI preferred) only with red flags or abnormal neurological examination.
• Blood tests for secondary causes only when indicated (ESR and CRP for age over 50).
• Screen for depression, anxiety, sleep disorder and medication overuse.
• Differentials: tension type headache (bilateral, pressing, mild to moderate, no nausea, not worsened by activity), cluster headache, medication overuse headache, sinus headache, subarachnoid haemorrhage, giant cell arteritis, raised intracranial pressure, idiopathic intracranial hypertension, cervicogenic headache, temporomandibular disorder, acute angle closure glaucoma.

Non-drug measures

• Education; regular meals, sleep, hydration and exercise (30 minutes of aerobic exercise 3 times a week); trigger identification without excessive avoidance; limit caffeine; relaxation, cognitive behavioural therapy and biofeedback; stop smoking; weight loss in obesity.

Acute treatment (treat early in the attack; use the lowest step that works)

• First step: take as early as possible during the headache phase:
  • Aspirin 900 mg orally (soluble, maximum 4 g daily; not under 16 years), or
  • Ibuprofen 400 to 600 mg orally (maximum 2.4 g daily; with food), or
  • Naproxen 500 to 750 mg orally (maximum 1.25 g daily), or
  • Diclofenac potassium 50 to 100 mg orally, or
  • Paracetamol 1 g orally (less effective; maximum 4 g daily).
  • Add an antiemetic: metoclopramide 10 mg orally, or domperidone 10 mg orally, or prochlorperazine 10 mg orally (or 3 mg buccal), up to 8 hourly. Metoclopramide also improves absorption. Limit metoclopramide to 5 days and avoid in young adults because of dystonic reactions; avoid domperidone in QT prolongation.
• Second step (if NSAID fails on 2 or 3 attacks): add a triptan taken at the start of headache (not during aura):
  • Sumatriptan 50 to 100 mg orally (repeat after 2 hours if the headache recurs, maximum 300 mg daily); 20 mg intranasally; 6 mg subcutaneously for rapid onset or vomiting (maximum 12 mg daily).
  • Rizatriptan 10 mg orally (5 mg if taking propranolol, maximum 15 mg daily; otherwise maximum 30 mg daily).
  • Zolmitriptan 2.5 to 5 mg orally or 5 mg intranasally (maximum 10 mg daily).
  • Eletriptan 40 mg orally (maximum 80 mg daily; avoid with strong CYP3A4 inhibitors such as clarithromycin and ketoconazole).
  • Naratriptan 2.5 mg orally (slower, fewer side effects, maximum 5 mg daily) and frovatriptan 2.5 mg (maximum 5 mg daily) for long attacks or recurrence.
  • Combination of sumatriptan 50 mg with naproxen 500 mg is more effective than either alone.
  • Contraindications: ischaemic heart disease, previous stroke or TIA, peripheral vascular disease, uncontrolled hypertension, hemiplegic or brainstem migraine, severe hepatic impairment (for sumatriptan); do not combine with ergotamine or within 24 hours, and use with caution with SSRIs (rare serotonin syndrome); wait 2 weeks after stopping MAO inhibitors.
  • Side effects: tingling, flushing, chest or throat tightness, drowsiness.
• Third step: gepants for those who fail or cannot use triptans: rimegepant 75 mg orally disintegrating tablet once daily as needed (maximum 75 mg in 24 hours), ubrogepant 50 to 100 mg (second dose after 2 hours; maximum 200 mg daily); lasmiditan 50 to 200 mg (no driving for 8 hours).
• Severe attacks with vomiting or status migrainosus: metoclopramide 10 mg IV or IM, then prochlorperazine 10 mg IV or IM, with IV fluids; ketorolac 30 mg IV or IM; sumatriptan 6 mg subcutaneously; dexamethasone 10 mg IV for prolonged attacks. Avoid opioids (including codeine and tramadol) and butalbital.
• Limit acute treatment to under 10 days a month for triptans and combination analgesics and under 15 days for simple analgesics.

Preventive treatment (offer if 4 or more migraine days a month, disabling attacks despite acute treatment, or contraindication to acute drugs)

• Propranolol 40 mg orally twice daily, increasing to 80 to 160 mg twice daily (or modified release 80 to 160 mg daily); avoid in asthma, heart block, bradycardia, and Raynaud disease.
• Metoprolol 50 mg twice daily increasing to 100 mg twice daily.
• Amitriptyline 10 mg at night, increasing by 10 mg every 1 to 2 weeks to 50 to 75 mg; useful with insomnia or tension type headache.
• Topiramate 25 mg at night, increasing weekly to 50 mg twice daily (maximum 100 mg twice daily); contraindicated in pregnancy; counsel on cognitive effects, paraesthesia, weight loss, glaucoma, kidney stones, and reduced effectiveness of oestrogen containing contraceptives.
• Candesartan 8 mg daily increasing to 16 mg daily (monitor renal function and potassium; avoid in pregnancy).
• Venlafaxine modified release 75 mg daily increasing to 150 mg (monitor blood pressure).
• Flunarizine 5 to 10 mg at night (may cause depression, weight gain and parkinsonism; avoid in depression and in older adults).
• Valproate is not used in women who could become pregnant.
• Anti-CGRP monoclonal antibodies (specialist, after at least 3 preventives fail): erenumab 70 mg or 140 mg subcutaneously monthly, fremanezumab 225 mg monthly or 675 mg every 3 months, galcanezumab 240 mg loading then 120 mg monthly, eptinezumab 100 to 300 mg IV every 12 weeks. Caution with constipation (erenumab), hypertension and Raynaud phenomenon.
• Atogepant 10 to 60 mg daily and rimegepant 75 mg every other day are oral gepant options.
• Onabotulinumtoxin A 155 units intramuscularly every 12 weeks for chronic migraine only.
• Allow 8 to 12 weeks at an adequate dose before judging benefit; review at 6 months and consider a taper after 6 to 12 months of good control.

Follow up and safety netting

• Review at 6 to 8 weeks after any change; use a diary. Advise urgent care for sudden severe headache, new neurological signs, fever with neck stiffness, headache after head injury, or a different pattern of headache.

Special groups

• Pregnancy and breastfeeding: paracetamol 1 g and metoclopramide 10 mg as first line; ibuprofen 400 mg may be used in the second trimester only (avoid after 20 weeks); sumatriptan 50 to 100 mg acceptable if needed; avoid topiramate, valproate, candesartan and ergotamine; propranolol or amitriptyline for prevention if necessary; aspirin avoided in breastfeeding.
• Women using oestrogen containing contraception: migraine without aura is not a contraindication unless other risk factors (age over 35 and smoking, hypertension, obesity, diabetes), but if aura develops, stop the oestrogen.
• Children (6 to 17 years): ibuprofen 10 mg/kg (maximum 400 mg) or paracetamol 15 mg/kg; sumatriptan nasal 10 to 20 mg from 12 years; prevention with propranolol 10 to 20 mg twice daily or amitriptyline 10 mg at night under specialist advice.
• Older adults: exclude giant cell arteritis; avoid triptans in vascular disease; use paracetamol; renal dose caution with NSAIDs.