Migraine

Epidemiology and Red Flags in Migraine

Prevalence and age of onset: Migraine affects approximately 15% of the adult population, with peak prevalence between 35–39 years.
Around 75% of individuals experience their first migraine before the age of 35.
Sex distribution:
- The female-to-male ratio is approximately 3:1 after puberty, likely due to the modulatory effects of oestrogen on the trigeminovascular system.
Red flag onset:
- The first onset of migraine-like symptoms after the age of 50 should prompt investigation for secondary headache causes, such as giant cell arteritis, intracranial mass lesions, or vascular events.
Family history:
- Risk of migraine is ≈ 50% if one parent is affected, and up to 75% if both are affected.
Neuroimaging is warranted for:
- New daily-persistent headache
- Headaches with neurological deficits
- Change in character or frequency of usual migraine
Medication-overuse headache (MOH):
- Risk with >15 days/month use of simple analgesics or >10 days/month use of triptans/opioids
- Must be addressed before commencing or adjusting prophylaxis

Common Migraine Triggers

Trigger Type	Examples	Notes
Dietary	– Tyramine (aged cheese) – phenylethylamine (chocolate) -MSG – aspartame – caffeine (excess or withdrawal) – nitrates (processed meats) – histamine (wine/beer)	Trigger response is highly individual—a food and symptom diary is more effective than broad exclusion. (Sources: Healthline, Migraine.com)
Hormonal	Oestrogen fluctuations – peri-menstrual – contraceptive use – pregnancy	Explains female predominance; menstrual migraine is a recognised subtype.
Environmental	– Bright or flickering lights – loud noises – strong smells (e.g. smoke, perfume)	Sensory hypersensitivity may begin in the premonitory phase.
Physiological	– Sleep irregularity (deprivation or excess) – dehydration – skipping meals – intense exertion – weather/altitude changes	Emphasise routine in sleep, hydration, and meals as part of preventive strategy.
Medication-related	Regular use of – simple analgesics – triptans – opioids – ergot derivatives	Risk of medication-overuse headache; requires weaning and prophylaxis initiation.

Frequency and Timing of Migraine Attacks

Attack frequency varies widely—from several per week to a few over a lifetime.
Migraines often begin in the early morning but can occur at any time, including waking the patient from sleep, likely due to fluctuations in brainstem trigeminovascular excitability.

ICHD-3 Migraine Classification

Primary Migraine Types

Migraine without aura (common form)
Migraine with aura, including:
- Typical aura with or without headache
- Brainstem aura (e.g. vertigo, dysarthria, ataxia)
- Hemiplegic migraine (familial or sporadic)
- Retinal migraine
Chronic migraine: >15 headache days/month for >3 months, with ≥8 migraine days
Complications: Status migrainosus, persistent aura without infarction, migrainous infarction, aura-triggered seizure

Episodic Syndromes Associated with Migraine

Cyclical vomiting syndrome
Abdominal migraine
Benign paroxysmal vertigo
Benign paroxysmal torticollis
Recurrent GI disturbance

ICHD-3 Diagnostic Criteria

Migraine Without Aura

Requires ≥ 5 attacks fulfilling all of the following:

Duration: 4–72 hours (2–72 hours in children)
Headache characteristics (≥ 2):
- Unilateral location (common but not universal)
- Pulsating/throbbing quality
- Moderate to severe intensity
- Aggravation by or avoidance of routine physical activity
Associated features (≥ 1):
- Nausea and/or vomiting
- Photophobia and phonophobia

Typical Aura (with or without headache)

Requires fully reversible aura symptoms affecting visual, sensory, or speech/language domains, with ≥2 of the following:

Gradual spread of symptoms over ≥5 minutes
Two or more symptoms occurring in succession
Each individual aura symptom lasting 5–60 minutes
At least one unilateral symptom
At least one positive symptom (e.g. flashing lights, tingling rather than loss of function)
Headache begins during the aura or within 60 minutes

four phases

Prodrome / aura / headache / postdrome

20% experience prodromal changes of hypothalamic involvement before the actual aura or pain commences.
- craving for food
- thirst
- fatigue/yawning
- irritability
- altered emotional states
33% experience an aura
- Visual auras
  - central loss of vision (central scotoma)
  - hemianopia
  - flickering lines
  - zig-zag formation

Sensory
- ‘pins and needles’/paraesthesiae
- Numbness usually starts in the hand, migrates up the arm, then involves the face, lips, and tongue
motor
speech aura
isolated typical aura without the headache– indicates a migraine.
- This is particularly important in the elderly where the headache of migraine is often absent, causing diagnostic confusion with transient ischaemic attacks. The aura of migraine is distinct, and quite different from vascular phenomena such as amaurosis fugax
60–94% have postdrome phase

Tips and traps in diagnosis: the three-question ID Migraine questionnaire

felt nauseated or sick in the stomach
were bothered by light (or a lot more than when they do not have headaches)
had limited ability to work, study or do what they needed to do for at least one day.

sensitivity of 84%
specificity of 76%
“yes” to 2/3 effectively identifies migraine sufferers

SNNOOP10 list of red and orange flags
Red flag	Related secondary headache
Systemic symptom/fever	Intracranial infection, carcinoid or phaeochromocytoma
History of neoplasm	Metastatic disease
Focal neurological deficit	Stroke, brain abscess or infection
Worse with eye movement and impaired vision	retrobulbar neuritis
Abrupt onset headache	Subarachnoid haemorrhage(thunderclap headache), pituitary apoplexy, reversible cerebral vasoconstriction syndrome, haemorrhage, cranial or cervical vascular pathology
Onset after the age of 50 years	Giant cell arteritis, neoplasm, mass lesion, vascular disorder, stroke
Change in pattern or recent onset	Neoplasm, headaches from vascular or non-vascular disorders
Positional headache	Intracranial hypertension or hypotension
Precipitated by sneeze/cough/exercise	Posterior fossa malformation, Chiari malformation
Papilloedema	Intracranial hypertension, mass lesions, venous sinus thrombosis
Progressive or atypical presentation	Neoplasm, non-vascular disorder
Pregnancy or puerperium	Postdural headache, pre-eclampsia, venous sinus thrombosis, hypothyroidism, diabetes, pituitary apoplexy, cranial or cervical vascular disorder
Painful eye/autonomic features	Pathology in posterior fossa, pituitary or cavernous sinus, Tolosa–Hunt syndrome or ophthalmic cause
Post-traumatic	Subdural haematoma or other vascular disorder
Pathology of immune system	Opportunistic infection or metastasis
Painkiller overuse or new medication	Medication-overuse headache or medication incompatibility

Neuroimaging Indications

First or worst severe Migraine Headache
New onset Migraine Headache in age over 50-55 years old
Sudden onset Headache
Abnormal Neurologic Examination
Not indicated in nonacute Migraine with normal exam

Treatment

Remove and avoid precipitants
- avoid triggers (stress, fatigues, hunger, chocolate, red wine, cheese)
- Avoid OCP (incr stroke risk in pt with migraine with aura, higher risk if >45, smoker)
- rest in dark, quiet room
Treatment of migraine is most effective if instigated at the onset of symptoms

Acute treatment

Mild/Moderate (<2 hours)

NSAID	Oral antiemetics
Aspalgin 900mg	metoclopramide 10mg orally
Panadeine/Aspirin combo	Prochlorperazine (Stemetil) (5–10 mg)
Naproxen 500–7500 mg	Domperidone (Motilium) (10 mg)
Ibuprofen 400–600 mg
diclofenac potassium 50mg

Note: 10% Caucasians/ 1-2% Asians are codeine ‘non-responders’, as they cannot metabolise codeine to morphine
Avoid NSAIDs in volume depletion, CCF, any impairment of renal function + with concomitant ACEI and or diuretics.

Moderate Migraine refractory to above

Consider administering at 1 hour for failed improvement with initial meds listed above
Triptan agents
- best given early when headache is mild, though not during the aura.
- 20-50% can relapse within 48 hr
- only triptans that have been shown to be effective in children are nasal sumatriptan and oral zolmitriptan
- All triptans are contraindicated in
  - known/possible CAD
  - within 24 hours of ergot-containing preparations
  - should be used with caution in patients on lithium, MAO inhibitors or SSRIs to avoid serotonin syndrome.
  - The symptoms of serotonin syndrome:
    - Autonomic: abdominal cramps, diarrhoea, hypotension or hypertension, tachycardia, profuse sweating, hyperpyrexia.
    - Cognitive: agitation, coma, confusion, disorientation.
    - Musculoskeletal: myoclonus, tremors
- Some patients respond better to a combination of a triptan and a nonopioid analgesic (eg aspirin, ibuprofen, naproxen)

eletriptan	40 to 80 mg orally	If symptoms recur, wait at least 2 hrs before repeat dose	max160 mg/24 hours
naratriptan	2.5 mg orally	If symptoms recur, wait at least 4 hrs before repeat dose	5mg/24 hours
rizatriptan	10 mg orally wafer	If symptoms recur, wait at least 2 hrs before repeat dose	max 30 mg/24 hours
sumatriptan	20 mg intranasally	If symptoms recur, wait at least 2 hrs before repeat dose	max 40 mg/24 hours
	50 to 100 mg orally	If symptoms recur, wait at least 2 hrs before repeat dose	max 300 mg/24 hours
	6mg SC	If symptoms recur, wait at least 1 hr before repeat dose	max12 mg/24 hours
zolmitriptan	2.5 mg orally	If symptoms recur, wait at least 2 hrs before repeat doseIf 2.5 mg tolerated but not effective in previous migraine, give 5 mg at onset of next migraine	max10 m/24 hours

Consider coadministration with NSAIDs (Indomethacin is available as a suppository)

Severe Migraine Headache (2-6 hours) – Intractable migraine (status migrainosus)

sumatriptan 6 mg	6mg SC	only if a triptan has not been given in the last 2 hours and a parenteral triptan has not been tried
ketorolac	30 mg IM	only if an oral NSAID has not been given in the last 4 to 6 hours
Chlorpromazine(Largactil)	12.5 mg in NS 0.9% 100 mL IV 30 min	exclude a prolonged QTc intervalfluid bolus to avoid hypotensionmax dose 37.5 mg (2x repeat infusion in needed)if acute dystonic reaction: benzatropine 1-2mg IV
dexamethasone	12 – 20 mg IV	Repeat after 12 hours if needed

Other

Ergotamine
- No longer available in Australia
- 1-2 mg: Oral, rectal, intranasal, parenteral
- Cheap and long-lasting
- is used together with caffeine.
  - Caffeine may result in tremors, insomnia and anxiety.
- Ergotamine is not recommended in children.
- should not be used in conjunction with macrolides antibiotics
- severe side effects
  - PUD
  - Rebound headache
  - more risk with CAD.
  - Do not use ergotamine if sumitriptan used in last 6 hours
Opioid analgesics
- should be considered as a last resort for acute headache management and if required should provoke a red flag consideration

Rebound/overuse headache

Medication overuse will result in a refractoriness of headache frequency , development of chronic daily headache and severity that is very difficult to break
if the patient is using rescue ergot preparations, analgesics (especially codeine), or triptans on more than 2 days per week, there is the real potential for rebound headache to develop
Overuse of acute antimigraine drugs frequently negates the effectiveness of prophylactic medication
Rx
- 3-week course of naproxen 250-500mg bd, taken regularly, may break the cycle of frequently recurring or unremitting headaches and the habit of responding to pain with analgesics.
- If it fails, it should not be repeated

General Measures

Avoid Stress bursts
- Spread home or work load out evenly
- Maintain good Posture
- Avoid craning neck forward
- Stay relaxed
Keep a Headache diary
- Record date, day of week, and time of day
- Record precipitating and relieving factors
Sleep Changes
- Avoid excessive Fatigue (get adequate sleep)
- Do not sleep later than normal on weekends
- Risk of let-down Headache
Habits
- Eat at regular times and do not miss meals
- Eliminate foods thought to provoke Headache
  - Alcohol
  - Red wines
- Limit foods associated with Rebound Headache
  - Caffeine sources (Tea, Coffee, Soda)
  - Analgesics
- Consider stopping provocative medications
  - Oral Contraceptives
Environmental
- Restrict physical exertion on hot days
- Avoid glare or exposure to flickering lights
- Avoid noise or strong smells

Prophylaxis

(if >1/12 depending on function of ADLs)
all these agents is to ‘start low and go slow
Where headaches occur more frequently than once per fortnight, prophylaxis should be offered and the choice determined by the headache type

Medication	Dosage	50% responder rate*	Regulatory status	Authors’ notes
Level A evidence – oral medications (EFNS or AAN)
Propranolol	40 mg (increase at intervals of one week or greater [ie ≥1 weekly] by 40 mg to maximum 40–160 mg total daily dose [BD or TDS])	30–40%	PBS: GB-M, TGA: Yes	Useful in anxiety, perimenopause; caution regarding mood and vivid dreams
Topiramate	25 mg (increase ≥1 weekly by 25 mg to maximum 50–100 mg BD)	46.3%	PBS: Auth-M, TGA: Yes	Useful for weight loss
Sodium valproate	200 mg (increase ≥1 weekly by 200 mg to maximum 200–600 mg BD)	42%	PBS: GB-O, TGA: No	Avoid in women of childbearing age
Flunarizine	5 mg (5–10 mg daily)	58.6%	PBS: No, TGA: SAS	Use with caution in individuals with depression
Level A evidence – injectable medications
OnabotulinumtoxinA	155 units, three times per month	47.1% in CM	PBS: Auth-M, TGA: Yes
Erenumab	140 mg, once per month	41% in CM	PBS: No, TGA: Yes
Fremanezumab	225 mg, once per month	47.7% in CM	PBS: Yes, TGA: Yes
Galcanezumab	240 mg, once per month	27.6% in CM	PBS: Yes, TGA: Yes
Level B evidence (EFNS or AAN)
Amitriptyline	10 mg (increase ≥1 weekly by 10 mg to 25–75 mg daily)	58.6%	PBS: GB-O, TGA: No	Useful for sleep/mood
Pizotifen	0.5 mg TID (1.5–3 mg/d)		PBS: Yes, TGA: Yes	Weight gain (21%–41%), sedation (37%–50%)
Venlafaxine	37.5 mg (increase ≥1 weekly by 37.5 mg to 75–150 mg daily)	28%	PBS: RB-O, TGA: No
Level C evidence (EFNS or AAN)
Candesartan	4 mg (increase ≥1 weekly by 4 mg to 8–32 mg daily)	40.4%	PBS: GB-O, TGA: No	Well tolerated
Gabapentin	300 mg (increase ≥3 days by 300 mg, 900–3600 mg total daily [BD or TDS])	46.4%	PBS: GB-O, TGA: No	Can be useful during perimenopausal
Magnesium	400 mg (400–600 mg daily elemental dose)	–	PBS: No, TGA: No	Well tolerated
Coenzyme Q10	150 mg (150–300 mg daily)	–	PBS: No, TGA: No	Well tolerated
Riboflavin	400 mg (400 mg daily)	–	PBS: No, TGA: No	Well tolerated
Other medications
Cyproheptadine	4 mg (4–12 mg daily)	–	PBS: No, TGA: Yes	Well tolerated
Melatonin	2 mg (4–8 mg daily)	54.4%	PBS: No, TGA: No
Lamotrigine	Pending interactions	46%	PBS: No, TGA: No	Useful with prominent aura symptoms/mood
Nortriptyline	10 mg (increase ≥1 weekly by 10 mg to 25–75 mg nocte)	28.6%	PBS: RB-O, TGA: No	Useful where amitriptyline is not tolerated

EFNS, European Federation of Neurological Societies

AAN, American Academy of Neurology;

Guide to choosing migraine prophylactic drugs

Tier (eTG / Australian Prescriber)	*Drugs that should* be tried in primary care**	PBS / TGA status ✱	Key points & typical “best-fit” comorbidities
First choices (“initial agents”)	• Propranolol 20 mg nocte → up-titrate • Candesartan 4 mg daily → 32 mg • Amitriptyline 10 mg nocte → 75 mg (or Nortriptyline) • Topiramate 25 mg nocte → 100 mg BD	All registered; PBS S85 (except candesartan on S85–CKD/HTN)	β-blocker aids tremor/anxiety candesartan useful with HTN/obesity TCA favours insomnia/depression topiramate assists weight loss but avoid in pregnancy
Second choices / “try next”	• Sodium valproate 200 mg nocte → 500 mg BD (avoid in women of child-bearing potential) • Verapamil SR 90 mg daily → 240 mg • Pizotifen 0.5 mg nocte → 1.5–3 mg	Valproate & verapamil off-label for migraine; PBS on S85 for epilepsy/arrhythmia	Valproate highly effective but teratogenic; verapamil preferred if β-blocker contraindicated; pizotifen very sedating/weight gain australianprescriber.tg.org.au
Specialist / limited-evidence options	• Metoprolol / Atenolol (if propranolol intolerant) • Flunarizine (TGA Special Access Scheme) • Gabapentin / Pregabalin, Venlafaxine, Lisinopril (off-label, weak data) • Onabotulinum toxin A (PBS item 5060Y; chronic migraine ≥15 days/month, failed ≥3 oral agents) • CGRP mAbs (erenumab, fremanezumab, galcanezumab) – TGA approved; erenumab on PBS since 2024 for chronic migraine meeting strict criteria	Flunarizine, gabapentin, lisinopril require SAS or private scripts	Reserve for refractory cases or where comorbidity is compelling; seek neurologist input australianprescriber.tg.org.au
Adjuncts / “evidence-limited but low-risk”	Magnesium (400–650 mg elemental), Riboflavin (B2 200 mg BD), Coenzyme Q10 150–300 mg/day	OTC	Trial ≥3 months; counsel regarding variable efficacy australianprescriber.tg.org.au

✱ PBS/TGA = registration or subsidy status for migraine prophylaxis unless otherwise stated.

Practical selection tips (match drug to patient)

Scenario	Preferred preventive
Hypertension / Metabolic syndrome	Candesartan, Propranolol
Insomnia / Depression	Amitriptyline (night dose)
Obesity or Weight-sensitive	Topiramate (weight loss); avoid pizotifen & valproate
Asthma / COPD	Avoid β-blockers → consider Candesartan, TCA
Child-bearing potential	Avoid Valproate, Topiramate, Flunarizine
Pregnancy / Planning	Non-drug measures ± Amitriptyline (low dose), Propranolol (1st–2nd trimester), Magnesium, Riboflavin

Migraine in children

Common causes of headaches
- febrile illnesses, with or without ear, nose and throat involvement
- migraines
- tension headaches
- meningitis
- space-occupying lesions
- subarachnoid haemorrhage
Red flags
- Acute and severe headache
- Progressive chronic headaches
- Focal neurology
- Age <3 years
- Headache/vomiting on waking
- Consistent location of recurrent headaches
- Presence of ventriculo-peritoneal shunt
- Hypertension
Migraines often short lived, resolve in 2-3 hours with sleep
Use ibuprofen first line, avoid aspirin – risk Reye syndrome
If nausea – ondansetron
Can use triptans in children > 6 years