Differentials by Age Group
Select an age band to view common diagnoses, secondary causes, and clinical pearls
Children & Adolescents (Under 18)
Most likely primary headaches
Secondary causes to consider
Clinical Pearls
Paediatric migraine is frequently bilateral and frontal — the absence of unilateral location does not exclude migraine in children.
Aura is less common in children than adults. Abdominal migraine and cyclic vomiting syndrome are recognised migraine equivalents.
Always check blood pressure (BP) and fundoscopy in any child with persistent unexplained headache — papilloedema signals raised Intracranial Pressure (ICP).
Idiopathic Intracranial Hypertension (IIH) predominantly affects overweight adolescent girls — key features include blurred vision, pulsatile tinnitus, and papilloedema.
Screen for screen time, caffeine intake, irregular sleep, and dehydration as modifiable triggers.
Young Adults (18–39)
Most likely primary headaches
Secondary causes to consider
Cluster Headache — Features, Acute Treatment & Why Refer
Clinical features: Strictly unilateral severe orbital or periorbital pain lasting 15 minutes to 3 hours, occurring up to 8 times per day. Autonomic features are characteristic: lacrimation, conjunctival injection, nasal congestion or rhinorrhoea, eyelid oedema, ptosis (Horner's syndrome). Patients are characteristically agitated and unable to rest — this distinguishes Cluster Headache from migraine (where patients prefer dark and quiet). Attacks cluster in bouts of weeks to months separated by remissions.
Acute treatment (both modalities require specialist input or initiation):
• Sumatriptan 6 mg subcutaneous (SC) — most effective acute agent; acts within 10–15 minutes. Can be self-administered. Limit to 2 injections per 24 hours.
• 100% high-flow Oxygen at 12–15 L/min for 15–20 minutes via non-rebreathe mask — effective in ~70% of attacks. Crucially, in NHS, home oxygen supply for Cluster Headache requires a specialist-initiated Home Oxygen Order Form (HOOF). This pathway cannot be initiated in primary care alone — Neurology referral is required to access this treatment.
• Sumatriptan 6 mg subcutaneous (SC) — most effective acute agent; acts within 10–15 minutes. Can be self-administered. Limit to 2 injections per 24 hours.
• 100% high-flow Oxygen at 12–15 L/min for 15–20 minutes via non-rebreathe mask — effective in ~70% of attacks. Crucially, in NHS, home oxygen supply for Cluster Headache requires a specialist-initiated Home Oxygen Order Form (HOOF). This pathway cannot be initiated in primary care alone — Neurology referral is required to access this treatment.
Prophylaxis — why specialist initiation is essential: Verapamil is the most effective preventative agent for Cluster Headache. However, doses required (typically 240–960 mg/day) are well above standard cardiac indications and require serial Electrocardiogram (ECG) monitoring at each dose increment (heart block, bradycardia, P-R prolongation). This titration must be conducted and supervised by a specialist. Transitional prophylaxis with a short course of prednisolone or suboccipital steroid injections may be used at Neurology to abort a cluster period acutely.
🏥 Refer to Neurology — Suggested (Urgent if severe / active cluster period): All suspected or confirmed Cluster Headache should be referred. Neurology is required for: (1) diagnostic confirmation and differentiation from Paroxysmal Hemicrania (PH) and Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) / Short-lasting Unilateral Neuralgiform headache attacks with Autonomic features (SUNA) — which respond to indomethacin and lamotrigine respectively rather than triptans; (2) initiating home oxygen via specialist pathway; (3) verapamil dose titration with Electrocardiogram (ECG) monitoring; (4) consideration of interventional procedures (greater occipital nerve block, sphenopalatine ganglion stimulation) for refractory cases.
NICE CG150 (2012, amended 2025) · BASH Cluster Headache Guidelines 2023 · NHS England Home Oxygen Service specification
New Daily Persistent Headache (NDPH) — Features & Why Refer
Defining feature: Daily and unremitting headache from a clearly remembered onset — patients can typically name the exact date. Onset is frequently preceded by a viral illness (e.g. influenza, Epstein-Barr Virus (EBV)) but can be spontaneous. There is no prior history of escalating episodic headache evolving into chronic headache — this distinguishes New Daily Persistent Headache (NDPH) from Chronic Migraine (CM) or Medication Overuse Headache (MOH).
Why it is refractory to standard treatment: New Daily Persistent Headache (NDPH) is thought to involve central sensitisation — likely triggered by a peripheral event (viral, inflammatory, or stressful) that leads to glial activation and sustained central pain processing changes. Once established, this mechanism is poorly responsive to standard analgesics, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and most preventative agents.
What Neurology does that primary care cannot:
• Magnetic Resonance Imaging (MRI) brain with contrast — to exclude low Cerebrospinal Fluid (CSF) pressure headache (spontaneous intracranial hypotension), Cerebral Venous Sinus Thrombosis (CVST), and inflammatory or structural causes
• Lumbar puncture with opening pressure measurement — to identify occult raised or low Cerebrospinal Fluid (CSF) pressure
• Specialist preventative trials: intravenous (IV) methylprednisolone, mexiletine, low-dose naltrexone, and nerve blocks have limited but reported benefit in this condition
• Realistic prognosis-setting: New Daily Persistent Headache (NDPH) may remit spontaneously (most likely in the first 2 years) but this is unpredictable; managing patient expectations is part of specialist care
• Magnetic Resonance Imaging (MRI) brain with contrast — to exclude low Cerebrospinal Fluid (CSF) pressure headache (spontaneous intracranial hypotension), Cerebral Venous Sinus Thrombosis (CVST), and inflammatory or structural causes
• Lumbar puncture with opening pressure measurement — to identify occult raised or low Cerebrospinal Fluid (CSF) pressure
• Specialist preventative trials: intravenous (IV) methylprednisolone, mexiletine, low-dose naltrexone, and nerve blocks have limited but reported benefit in this condition
• Realistic prognosis-setting: New Daily Persistent Headache (NDPH) may remit spontaneously (most likely in the first 2 years) but this is unpredictable; managing patient expectations is part of specialist care
🏥 Refer to Neurology — Suggested (Routine unless red flags present): All new cases of New Daily Persistent Headache (NDPH). Secondary causes (raised Intracranial Pressure (ICP), low Cerebrospinal Fluid (CSF) pressure, Cerebral Venous Sinus Thrombosis (CVST)) must be actively excluded by imaging and Cerebrospinal Fluid (CSF) analysis before this diagnosis is applied. Standard primary care analgesics and first-line preventatives are typically ineffective without addressing the underlying central mechanism.
BASH Guidelines 2023 · NICE CG150 (amended 2025) · International Classification of Headache Disorders 3rd edition (ICHD-3), Section 4.10
Other Clinical Pearls (18–39)
This is the peak presentation age for migraine. Establish full headache history including frequency and analgesia use at the first consultation.
Combined Oral Contraceptive Pill (COCP) is contraindicated in migraine with aura — UK Medical Eligibility Criteria (UKMEC) Category 4 (unacceptable health risk due to substantially increased stroke risk). Progestogen-only methods are safe (UKMEC Category 2).
Screen for analgesic overuse at every consultation — Medication Overuse Headache (MOH) is common in this age group and is highly modifiable.
Middle Age (40–59)
Most likely primary headaches
Secondary causes to consider
Clinical Pearls
Migraine often worsens permenopausally due to oestrogen flux, then typically improves post-menopause. A changing headache pattern warrants reassessment rather than re-labelling.
Hormone Replacement Therapy (HRT) — particularly transdermal (rather than oral) oestrogen — may stabilise oestrogen levels and reduce migraine frequency. See HRT Navigator for prescribing detail.
Acute angle-closure glaucoma: periorbital pain, coloured halos around lights, blurred vision, raised Intraocular Pressure (IOP), and nausea — same-day ophthalmology emergency.
Obstructive Sleep Apnoea (OSA) morning headache: bilateral, diffuse, resolves within 30 minutes of waking. Ask about snoring, witnessed apnoeas, and excessive daytime somnolence — refer for sleep study if suspected.
New daily or progressive headache in this age group requires imaging before applying a primary headache label.
Giant Cell Arteritis (GCA) must be excluded in any new headache in a patient over 50. Permanent visual loss may occur within hours of onset of visual symptoms. Do not delay corticosteroids pending biopsy — see Giant Cell Arteritis (GCA) tab.
Over 50s
Most likely primary headaches
Important secondary causes — must not miss
Trigeminal Neuralgia (TN) — Features, First-Line Treatment & Why Refer
Clinical features: Brief (seconds), severe, electric-shock or lancinating quality unilateral facial pain in the distribution of V2 (maxillary) or V3 (mandibular) branches of the trigeminal nerve. Triggered by eating, talking, touching the face, brushing teeth, or cold air. Pain-free intervals between attacks are characteristic and help distinguish Trigeminal Neuralgia (TN) from other facial pain syndromes.
First-line treatment (can be initiated in primary care pending referral): Carbamazepine 100–200 mg twice daily (BD), titrated cautiously to 600–800 mg/day divided as tolerated. Check Full Blood Count (FBC), Urea & Electrolytes (U&E), and Liver Function Tests (LFTs) at baseline. Arrange HLA-B*1502 testing before initiation in patients of South Asian, South East Asian, or Han Chinese descent (risk of Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN)).
🏥 Refer to Neurology — Suggested (Routine, or urgent if atypical features): All new or suspected Trigeminal Neuralgia (TN) requires neuroimaging. Neurology referral enables:
• Magnetic Resonance Imaging (MRI) brain with dedicated trigeminal nerve sequence — to exclude:
— Demyelination: Multiple Sclerosis (MS) is found in ~4% of Trigeminal Neuralgia (TN) cases; more likely in patients under 50, women, and those with bilateral or atypical distribution
— Vascular compression of the trigeminal nerve root entry zone — identifies candidacy for Microvascular Decompression (MVD), a highly effective neurosurgical procedure with 70–80% long-term pain-free rates
— Posterior fossa tumour, arteriovenous malformation, or other structural cause
• Expert guidance on drug titration, monitoring, and tolerability
• Assessment for procedural interventions: Gamma Knife Stereotactic Radiosurgery (GKRS), percutaneous balloon microcompression, or glycerol rhizotomy for those not suitable for, or failing, Microvascular Decompression (MVD) NICE CG156 Trigeminal Neuralgia (2013) · European Academy of Neurology (EAN) / European Federation of Neurological Societies (EFNS) Trigeminal Neuralgia (TN) Guidelines 2019 · BASH Guidelines 2023
• Magnetic Resonance Imaging (MRI) brain with dedicated trigeminal nerve sequence — to exclude:
— Demyelination: Multiple Sclerosis (MS) is found in ~4% of Trigeminal Neuralgia (TN) cases; more likely in patients under 50, women, and those with bilateral or atypical distribution
— Vascular compression of the trigeminal nerve root entry zone — identifies candidacy for Microvascular Decompression (MVD), a highly effective neurosurgical procedure with 70–80% long-term pain-free rates
— Posterior fossa tumour, arteriovenous malformation, or other structural cause
• Expert guidance on drug titration, monitoring, and tolerability
• Assessment for procedural interventions: Gamma Knife Stereotactic Radiosurgery (GKRS), percutaneous balloon microcompression, or glycerol rhizotomy for those not suitable for, or failing, Microvascular Decompression (MVD) NICE CG156 Trigeminal Neuralgia (2013) · European Academy of Neurology (EAN) / European Federation of Neurological Societies (EFNS) Trigeminal Neuralgia (TN) Guidelines 2019 · BASH Guidelines 2023
Other Clinical Pearls (Over 50s)
New migraine after age 50 is rare — consider intracranial pathology and arrange imaging before applying a primary headache diagnosis.
Subdural Haematoma (SDH) may follow trivial or entirely unrecalled head injury, particularly in anticoagulated patients or those with frequent falls. Computed Tomography (CT) brain without contrast is the diagnostic investigation of choice.
Normal Pressure Hydrocephalus (NPH) clinical triad: cognitive decline + gait apraxia ("magnetic gait") + urinary incontinence — refer to Neurology or Neurosurgery for assessment and imaging.
Tension-Type Headache (TTH)
NICE CG150 (2012, amended 2025) · British Association for the Study of Headache (BASH) Guidelines 2023
Diagnostic Features
Required features (all must be present)
Bilateral, pressing or tightening quality — non-pulsating
Mild to moderate intensity
Not aggravated by routine physical activity
No nausea or vomiting
Photophobia OR phonophobia (not both simultaneously)
Frequency classification
Infrequent Episodic Tension-Type Headache (TTH): <1 day/month
Frequent Episodic Tension-Type Headache (TTH): 1–14 days/month for >3 months
Chronic Tension-Type Headache (CTTH): ≥15 days/month for >3 months
⚠️ Screen for Medication Overuse Headache (MOH) Before Adding Prophylaxis
If the patient is using simple analgesics on ≥15 days/month, or opioids / triptans on ≥10 days/month for >3 months, address Medication Overuse Headache (MOH) first — adding prophylaxis without treating overuse is ineffective. See the Medication Overuse tab.
Acute Treatment
Limit acute analgesic use to ≤15 days/month. Frequent use — especially opioids and combination preparations — causes Medication Overuse Headache (MOH). (NICE CG150)
| Drug | Dose | Max Daily | Notes |
|---|---|---|---|
| Ibuprofen | 400 mg | 3 doses | Non-Steroidal Anti-Inflammatory Drug (NSAID). Take with food. Avoid if gastrointestinal (GI) or renal risk. Best evidence base for Tension-Type Headache (TTH) among simple analgesics. |
| Aspirin | 600–900 mg | 4 doses | Avoid in patients under 16. Soluble formulation preferred for faster absorption. |
| Paracetamol | 1 g (1000 mg) | 4 doses | Safest profile. Less effective than Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for Tension-Type Headache (TTH). First choice in pregnancy or when NSAIDs contraindicated. |
Avoid
Opioids and combination analgesic preparations carry a high Medication Overuse Headache (MOH) risk and are not recommended for Tension-Type Headache (TTH). (NICE CG150)
Prophylaxis — Chronic Tension-Type Headache (CTTH) (≥15 days/month)
First-Line
| Drug | Starting Dose | Target Range | Evidence & Notes |
|---|---|---|---|
| Amitriptyline | 10 mg nocte | 10–75 mg nocte | Best evidence for Chronic Tension-Type Headache (CTTH) prophylaxis — Number Needed to Treat (NNT) ~3.6 at 75 mg. Titrate by 10–25 mg every 2–4 weeks. Common effects: sedation, dry mouth, constipation. Obtain Electrocardiogram (ECG) if dose >40 mg or cardiac risk factors. Follow NICE NG46 guidance on safe prescribing and withdrawal of antidepressants. |
Alternatives if Amitriptyline Not Tolerated
| Drug | Dose | Notes |
|---|---|---|
| Mirtazapine | 15–30 mg nocte | Noradrenergic and Specific Serotonergic Antidepressant (NaSSA). Useful if amitriptyline not tolerated. Weight gain is common. Off-label use for headache. |
| Venlafaxine | 37.5–150 mg daily | Serotonin-Norepinephrine Reuptake Inhibitor (SNRI). Off-label. Evidence base exists. Discontinuation syndrome — always taper. Blood pressure (BP) monitoring at higher doses. |
Non-Pharmacological (NICE Recommended)
Acupuncture is NICE-recommended when pharmacological prophylaxis has failed or is contraindicated. (NICE CG150, amended 2025)
Migraine
NICE CG150 (2012, amended June 2025) · British Association for the Study of Headache (BASH) 2023 · Scottish Intercollegiate Guidelines Network (SIGN) 155 (2018)
Diagnostic Criteria
Migraine Without Aura (≥5 attacks, 4–72 hours)
At least 2 of 4: Unilateral · Pulsating · Moderate or severe intensity · Aggravated by routine activity
At least 1 of 2: Nausea or vomiting · Photophobia AND phonophobia
Migraine With Aura (typical — fully reversible)
Visual (scotoma, zigzag fortification spectra), sensory, or speech symptoms
Gradual onset ≥5 minutes; duration 20–60 minutes
Followed by or occurring simultaneously with headache
Hemiplegic Aura — Specialist Assessment Required
Contraceptive safety: Do not prescribe the Combined Oral Contraceptive Pill (COCP) in any patient with hemiplegic aura — UK Medical Eligibility Criteria (UKMEC) Category 4 (unacceptable health risk; substantially elevated stroke risk). Progestogen-only contraception is safe (UK Medical Eligibility Criteria (UKMEC) Category 2).
Avoid triptans in hemiplegic migraine — relatively contraindicated due to vasoconstrictive mechanism. Discuss with Neurology before prescribing any acute specific treatment.
Hemiplegic migraine includes Familial Hemiplegic Migraine (FHM) (autosomal dominant; gene mutations in CACNA1A, ATP1A2, SCN1A) and Sporadic Hemiplegic Migraine (SHM). Both subtypes require specialist neurological assessment.
Avoid triptans in hemiplegic migraine — relatively contraindicated due to vasoconstrictive mechanism. Discuss with Neurology before prescribing any acute specific treatment.
Hemiplegic migraine includes Familial Hemiplegic Migraine (FHM) (autosomal dominant; gene mutations in CACNA1A, ATP1A2, SCN1A) and Sporadic Hemiplegic Migraine (SHM). Both subtypes require specialist neurological assessment.
🏥 Refer to Neurology — Suggested (Urgent for first episode or diagnostic uncertainty):
• Magnetic Resonance Imaging (MRI) brain with Diffusion-Weighted Imaging (DWI) — to exclude stroke / Transient Ischaemic Attack (TIA) and structural cause; motor symptoms mandate urgent imaging
• Assessment for CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) — a hereditary small vessel disease that can mimic hemiplegic migraine with cognitive decline and leukoaraiosis on Magnetic Resonance Imaging (MRI)
• Genetic counselling and testing if Familial Hemiplegic Migraine (FHM) is suspected — autosomal dominant with high penetrance; implications for family members
• Specialist-guided prophylaxis: flunarizine, verapamil, and lamotrigine have reported benefit; standard preventatives (propranolol, topiramate) have limited evidence in this subtype BASH Guidelines 2023 · NICE CG150 (amended 2025) · UK Medical Eligibility Criteria (UKMEC) 2016 (updated 2019) · International Classification of Headache Disorders 3rd edition (ICHD-3) Section 1.2.3
• Magnetic Resonance Imaging (MRI) brain with Diffusion-Weighted Imaging (DWI) — to exclude stroke / Transient Ischaemic Attack (TIA) and structural cause; motor symptoms mandate urgent imaging
• Assessment for CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) — a hereditary small vessel disease that can mimic hemiplegic migraine with cognitive decline and leukoaraiosis on Magnetic Resonance Imaging (MRI)
• Genetic counselling and testing if Familial Hemiplegic Migraine (FHM) is suspected — autosomal dominant with high penetrance; implications for family members
• Specialist-guided prophylaxis: flunarizine, verapamil, and lamotrigine have reported benefit; standard preventatives (propranolol, topiramate) have limited evidence in this subtype BASH Guidelines 2023 · NICE CG150 (amended 2025) · UK Medical Eligibility Criteria (UKMEC) 2016 (updated 2019) · International Classification of Headache Disorders 3rd edition (ICHD-3) Section 1.2.3
Frequency Classification
Acute Treatment — Step Approach
Give treatment at headache onset, not during prodrome. Add an antiemetic to any step — Metoclopramide also improves gastric motility and enhances absorption of co-administered analgesics. (NICE CG150)
Step 1 — Simple Analgesics (mild-moderate attacks, or triptan-naïve)
▼| Drug | Dose | Notes |
|---|---|---|
| Ibuprofen | 400–600 mg at onset | Non-Steroidal Anti-Inflammatory Drug (NSAID) first-line if no contraindication |
| Aspirin | 900 mg at onset + antiemetic | Soluble preferred. Add Metoclopramide 10 mg routinely. |
| Paracetamol | 1 g (1000 mg) at onset | Less effective than Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Use if Non-Steroidal Anti-Inflammatory Drug (NSAID) contraindicated. |
Step 2 — Triptans (if Step 1 fails, or moderate-severe from onset)
▼Limit triptan use to ≤10 days/month to avoid Medication Overuse Headache (MOH). Contraindicated in: coronary artery disease, uncontrolled hypertension, hemiplegic migraine, basilar migraine, within 24 hours of ergotamine. (NICE CG150)
| Drug | Dose / Route | Notes |
|---|---|---|
| Sumatriptan ★ | 50–100 mg oral · 10–20 mg nasal · 6 mg subcutaneous (SC) | Most evidence. Subcutaneous (SC) preferred if vomiting prominent; acts within 15–20 min. May repeat after 2 hours if headache returns. |
| Rizatriptan | 10 mg oral (5 mg if on Propranolol) | Faster onset. Wafer formulation useful with nausea. Reduce dose to 5 mg if co-prescribed with Propranolol (pharmacokinetic interaction). |
| Zolmitriptan | 2.5–5 mg oral or 5 mg nasal | Nasal route useful with prominent nausea. |
| Eletriptan | 40–80 mg oral | Higher efficacy; longer half-life with less headache recurrence within 24 hours. |
| Almotriptan | 12.5 mg oral | Good tolerability. Useful if side effects limit other triptans. |
Antiemetics — Add to Any Step
▼| Drug | Dose | Notes |
|---|---|---|
| Metoclopramide | 10 mg oral or intramuscular (IM) | Dopamine antagonist. Improves gastric motility — enhances absorption of co-administered analgesics. Avoid prolonged use (tardive dyskinesia risk). MHRA 2014 restrictions on dose and duration apply. |
| Prochlorperazine | 3–6 mg buccal / 12.5 mg intramuscular (IM) | Buccal absorption useful when vomiting prevents oral medication. Intramuscular (IM) in out-of-hours or acute settings. |
| Domperidone | 10 mg oral | Does not cross blood-brain barrier (BBB) — fewer central side effects. Cardiac QT prolongation caution — avoid in hepatic impairment and with QT-prolonging drugs. |
Prophylaxis
Offer prophylaxis if: ≥4 migraine days/month · OR significant disability (Migraine Disability Assessment (MIDAS) grade ≥11) · OR frequent acute medication use. Review response at 6 months. (NICE CG150, amended June 2025)
NICE CG150 Update — June 2025: The recommendation for all three first-line agents has been changed from "offer" to "consider" — Propranolol, Topiramate, and Amitriptyline are now positioned as equal options. No single agent is preferred. Selection must be individualised based on patient profile, comorbidities, contraindications, and reproductive status. Try each in turn if the first is ineffective or not tolerated.
Topiramate — MHRA Pregnancy Prevention Programme (PPP), June 2024: Topiramate must not be prescribed to women of childbearing potential unless all Pregnancy Prevention Programme (PPP) conditions are met: (1) two documented negative pregnancy tests, (2) use of highly effective contraception throughout treatment and for ≥4 weeks after stopping, (3) annual review with signed patient acknowledgement card. Topiramate is associated with a 2–3× increased risk of intellectual disability, Autism Spectrum Disorder (ASD), and Attention Deficit Hyperactivity Disorder (ADHD) in children exposed in utero. (MHRA Drug Safety Update, June 2024)
Topiramate — MHRA Pregnancy Prevention Programme (PPP), June 2024: Topiramate must not be prescribed to women of childbearing potential unless all Pregnancy Prevention Programme (PPP) conditions are met: (1) two documented negative pregnancy tests, (2) use of highly effective contraception throughout treatment and for ≥4 weeks after stopping, (3) annual review with signed patient acknowledgement card. Topiramate is associated with a 2–3× increased risk of intellectual disability, Autism Spectrum Disorder (ASD), and Attention Deficit Hyperactivity Disorder (ADHD) in children exposed in utero. (MHRA Drug Safety Update, June 2024)
First-Line — Consider any of the following (NICE CG150, June 2025)
| Drug | Start | Target | Key Considerations |
|---|---|---|---|
| Propranolol | 40 mg twice daily (BD) | 40–240 mg/day | Beta-blocker. Avoid in asthma, depression (note Healthcare Safety Investigation Branch (HSIB) alert — propranolol carries significant overdose risk in patients with depression and migraine, June 2024), Raynaud's phenomenon, and insulin-dependent diabetes. Reduce Rizatriptan dose to 5 mg if co-prescribing. Long-acting (LA) preparation available. |
| Topiramate | 25 mg nocte | 25–100 mg/day (divided) | MHRA Pregnancy Prevention Programme (PPP) mandatory before prescribing to any woman of childbearing potential. Common effects: cognitive slowing ("topiramate fog"), word-finding difficulty, weight loss, paraesthesia, renal stones. Highly teratogenic — increased risk of oral cleft, low birth weight, and neurodevelopmental disorders in children exposed in utero. (MHRA June 2024) |
| Amitriptyline | 10 mg nocte | 10–75 mg nocte | Off-label for migraine (licensed for depression; NICE CG150 now includes as equal option). Useful if comorbid poor sleep, Tension-Type Headache (TTH) overlap, or anxiety. Follow NICE NG46 safe prescribing and withdrawal guidance. Obtain Electrocardiogram (ECG) if dose >40 mg or cardiac risk factors present. |
If the first agent tried does not work or is not tolerated, try the second and then the remaining option, unless contraindicated by safety concerns. (NICE CG150, 2025)
Second-Line / Off-Label Options
| Drug | Dose | Notes |
|---|---|---|
| Candesartan | 8–16 mg daily | Angiotensin Receptor Blocker (ARB). Off-label for migraine. Well tolerated. Useful if comorbid hypertension. Evidence from randomised controlled trials (Tronvik et al.). |
| Sodium Valproate | 400–1000 mg daily | Contraindicated in women and girls of childbearing potential unless enrolled in MHRA Pregnancy Prevention Programme (PPP). Two-specialist sign-off required for new prescribing in women under 55. NHS England restricted. (MHRA Jan 2024, updated Feb 2025) |
| Pizotifen | 0.5–1.5 mg nocte | Weight gain and sedation commonly limit use. Weaker evidence base. Use only if first-line options are exhausted or contraindicated. |
| Gabapentin | — | Do not offer Gabapentin for migraine prophylaxis. Explicitly not recommended by NICE CG150 (2015, reaffirmed 2025). |
Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies — Specialist-Initiated
NICE Technology Appraisals (TA) 697 / 864: Erenumab (Aimovig) · Fremanezumab (Ajovy) · Galcanezumab (Emgality) · Eptinezumab (Vyepti — intravenous (IV)).
Eligibility criteria: ≥4 migraine days/month AND failure of ≥3 preventatives, OR Chronic Migraine (CM). Must be initiated by Neurology or a Headache Specialist. May subsequently be monitored and repeated in primary care. Review efficacy at 3–6 months.
Eligibility criteria: ≥4 migraine days/month AND failure of ≥3 preventatives, OR Chronic Migraine (CM). Must be initiated by Neurology or a Headache Specialist. May subsequently be monitored and repeated in primary care. Review efficacy at 3–6 months.
Non-Pharmacological (NICE Recommended)
Menstrual Migraine — Perimenstrual Mini-Prophylaxis
For predictable perimenstrual attacks (typically day -2 to +3 of menstruation). Consider short-course perimenstrual treatment when attacks are predictable and disabling.
| Drug | Dose & Timing | Notes |
|---|---|---|
| Frovatriptan | 2.5 mg twice daily (BD), days -2 to +3 | Longest half-life triptan (~26 hours) — British Association for the Study of Headache (BASH) recommended for perimenstrual use due to sustained coverage and low recurrence rate. |
| Mefenamic acid | 500 mg three times daily (TDS) perimenstrually | Non-Steroidal Anti-Inflammatory Drug (NSAID). Also useful for dysmenorrhoea — dual benefit. Take with food. |
| Transdermal oestrogen | 100 mcg patch, days -3 to +5 | Stabilises the oestrogen withdrawal drop that triggers perimenstrual attacks. Discuss via Hormone Replacement Therapy (HRT) or hormonal contraception pathway — see HRT Navigator. |
Giant Cell Arteritis (GCA)
British Society for Rheumatology (BSR) GCA Guidelines 2020 · Medical Emergency
MEDICAL EMERGENCY. Permanent visual loss can occur within hours of the onset of visual symptoms. Do not delay prednisolone pending biopsy or specialist review. Temporal Artery Biopsy (TAB) remains positive for up to 2 weeks after starting corticosteroids — delay of treatment is never justified by biopsy logistics.
Open Giant Cell Arteritis (GCA) Navigator
Full diagnostic scoring (American College of Rheumatology (ACR) criteria), same-day treatment dosing, corticosteroid tapering protocol, monitoring schedule with Erythrocyte Sedimentation Rate (ESR) / C-Reactive Protein (CRP) targets, and Temporal Artery Biopsy (TAB) referral guidance — in a dedicated clinical decision support tool.
→
Clinical Features — When to Suspect Giant Cell Arteritis (GCA)
Classic features
New headache in patient >50 years
Temporal artery tenderness or reduced pulsation on palpation
Jaw claudication (pain on chewing that ceases with rest)
Scalp tenderness (pain on combing hair)
Visual disturbance — amaurosis fugax, diplopia, sudden permanent visual loss
Associated features
Constitutional symptoms: fever, fatigue, night sweats, unexplained weight loss
Polymyalgia Rheumatica (PMR) — bilateral shoulder and hip girdle stiffness lasting >45 minutes on waking
Key investigations
Immediate Management
Low Risk — No Visual Symptoms
Prednisolone 40–60 mg oral — start same day. Refer urgently to Rheumatology. Arrange Temporal Artery Biopsy (TAB) without delay. (British Society for Rheumatology (BSR) GCA Guidelines 2020)
High Risk — Visual Symptoms Present
999 / Emergency admission. Intravenous (IV) Methylprednisolone 500–1000 mg daily × 3 days. Same-day Ophthalmology referral.
For full corticosteroid tapering schedule, monitoring intervals, and Erythrocyte Sedimentation Rate (ESR) / C-Reactive Protein (CRP) targets — use the Giant Cell Arteritis (GCA) Navigator. (British Society for Rheumatology (BSR) GCA Guidelines 2020)
Medication Overuse Headache (MOH)
NICE CG150 (2012, amended 2025) · British Association for the Study of Headache (BASH) Guidelines 2023
Definition
Headache on ≥15 days/month in a patient with a pre-existing primary headache disorder who has used acute medication on:
Medication Overuse Headache (MOH) is the most common cause of transformed or chronic daily headache in primary care. Prophylaxis is ineffective while overuse continues — always address Medication Overuse Headache (MOH) first. (NICE CG150 · BASH 2023)
Management Steps
1. Explain and counsel: Explain the paradox — the medication is causing the headaches. Reassure that withdrawal is effective in 70–80% of cases. Provide written information. Validate that the withdrawal period will feel worse before it improves — this prevents early abandonment of the process.
2. Withdraw the overused drug: Abrupt withdrawal is preferred for triptans and ergotamines. Gradual reduction for opioids (with addiction service support if required). Sustained Non-Steroidal Anti-Inflammatory Drug (NSAID) or Paracetamol overuse can be stopped abruptly with bridge coverage.
3. Bridge therapy: Naproxen 500 mg twice daily (BD) for 2–4 weeks can reduce withdrawal headache severity, provided Naproxen was not the overused drug.
4. Warn about withdrawal worsening: Headache severity typically worsens in the first 2–4 weeks. This is an expected and transient withdrawal phenomenon — not treatment failure.
5. Start prophylaxis after withdrawal: Begin appropriate prophylaxis once the overuse pattern has broken (typically 4 weeks). For migraine-predominant Medication Overuse Headache (MOH), Topiramate may have some efficacy even during the withdrawal period.
6. Follow up at 4–8 weeks: Review headache diary, medication use, and response. Consider Neurology referral if withdrawal unsuccessful after two attempts — specialist inpatient or day-case withdrawal protocols exist for refractory cases. (BASH 2023)
Success rate: ~70–80% of patients improve significantly within 2–4 months of successful withdrawal, with meaningful reduction in headache day frequency. (BASH 2023 · NICE CG150)
Key Drug Interactions — Headache Medications
Clinically significant interactions relevant to headache prescribing. Always verify against current British National Formulary (BNF) / MHRA Summary of Product Characteristics (SmPC) before prescribing.
Triptans
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Any Triptan | SSRIs / SNRIs (Fluoxetine, Sertraline, Venlafaxine etc.) |
Serotonin syndrome risk — additive serotonergic effect. Risk is low in practice but increases at higher doses or combinations. Features: agitation, tremor, hyperthermia, clonus, hyperreflexia. | Caution — not an absolute contraindication. Counsel patient on symptoms. Avoid Tramadol combination (higher risk). (MHRA 2006 · BNF) |
| Any Triptan | MAOIs / Moclobemide | Contraindicated — severe serotonin toxicity risk. Monoamine Oxidase Inhibitor (MAOI) inhibits triptan metabolism → dangerously elevated plasma levels. | Absolute contraindication. Allow 14-day washout after stopping irreversible MAOI before prescribing any triptan. (BNF) |
| Any Triptan | Ergotamine / Methysergide | Additive vasoconstrictive effect — risk of severe prolonged vasospasm / ischaemia. | Contraindicated — minimum 24-hour separation required between ergotamine and any triptan. (NICE CG150 · BNF) |
| Rizatriptan | Propranolol | Pharmacokinetic interaction — Propranolol inhibits Rizatriptan metabolism via Monoamine Oxidase A (MAO-A), raising Rizatriptan plasma levels by ~70%. | Reduce Rizatriptan dose to 5 mg (from 10 mg) in patients also taking Propranolol. (BNF · Rizatriptan SmPC) |
Topiramate
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Topiramate | Combined Oral Contraceptive Pill (COCP) | Enzyme induction at higher doses (≥200 mg/day) — Topiramate induces CYP3A4, reducing oestrogen and progestogen plasma levels and contraceptive efficacy. At standard migraine prophylaxis doses (≤100 mg/day) the risk is lower but not absent. Critical given Pregnancy Prevention Programme (PPP) requirements. | Use alternative highly effective contraception (intrauterine device (IUD), implant, or injectable) — not the Combined Oral Contraceptive Pill (COCP) alone. Mandatory under MHRA Pregnancy Prevention Programme (PPP). (MHRA June 2024 · Topiramate SmPC) |
| Topiramate | Valproate | Hyperammonaemia with encephalopathy — combination increases ammonia levels, even without hepatic disease. Can occur at therapeutic doses of both drugs. | Avoid combination where possible. If co-prescribed, monitor for confusion, lethargy, cognitive changes — check serum ammonia. (BNF · MHRA) |
| Topiramate | Lithium | Topiramate-induced nephrolithiasis and hypokalaemia may affect Lithium clearance — risk of Lithium toxicity. | Monitor Lithium levels closely if co-prescribed. Ensure adequate hydration. (BNF) |
| Topiramate | Carbonic anhydrase inhibitors (Acetazolamide, Zonisamide) |
Additive renal stone risk — both inhibit carbonic anhydrase, increasing urinary pH and calcium phosphate stone formation. | Avoid combination. If unavoidable, ensure high fluid intake (>2L/day) and monitor renal function. (Topiramate SmPC) |
Propranolol
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Propranolol | Verapamil | Additive negative chronotropy and inotropy — both drugs slow atrioventricular (AV) conduction. Combination risk: complete heart block, severe bradycardia, haemodynamic compromise. | Contraindicated together in most circumstances. Do not co-prescribe without specialist cardiology input. (BNF) |
| Propranolol | Adrenaline (Epinephrine) | Paradoxical hypertension — beta-blockade leaves alpha-adrenergic vasoconstriction unopposed when adrenaline given, causing severe hypertensive response. | Alert anaesthetist / emergency team if patient on Propranolol. Relevant for allergy management and surgical settings. (BNF) |
| Propranolol | Insulin / oral hypoglycaemics | Masks hypoglycaemia symptoms — beta-blockade blunts tachycardia (key warning sign) and delays recovery from hypoglycaemia. | Avoid in insulin-dependent diabetes where possible. If used, counsel patient and carer on alternative hypoglycaemia symptoms (sweating, pallor). (BNF) |
Amitriptyline
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Amitriptyline | SSRIs / SNRIs | Additive serotonin effect + QTc prolongation — Fluoxetine and Paroxetine also inhibit CYP2D6, raising Amitriptyline plasma levels significantly, increasing cardiotoxicity risk. | If combination unavoidable, use lowest effective dose of Amitriptyline and monitor Electrocardiogram (ECG). Avoid Fluoxetine or Paroxetine co-prescription — use Sertraline or Citalopram (less CYP2D6 inhibition) if antidepressant needed. (BNF) |
| Amitriptyline | QT-prolonging drugs (Domperidone, Haloperidol, Azithromycin, Ondansetron) |
Additive QTc prolongation — risk of Torsades de Pointes (TdP) / ventricular arrhythmia, particularly at higher doses or in patients with hypokalaemia. | Obtain baseline Electrocardiogram (ECG). Review full medication list. Correct electrolytes before initiating. Use crediblemeds.org for updated QT risk categorisation. (BNF · MHRA) |
| Amitriptyline | MAOIs | Severe serotonin syndrome / hypertensive crisis — potentially fatal combination. | Absolute contraindication. 14-day washout required after irreversible MAOI; 24 hours after Moclobemide. (BNF) |
Sodium Valproate
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Valproate | Lamotrigine | Valproate markedly inhibits Lamotrigine glucuronidation — doubles Lamotrigine half-life and plasma levels, dramatically increasing Stevens-Johnson Syndrome (SJS) risk. | If combination required (specialist only), halve Lamotrigine titration rate and target dose. (BNF · Lamotrigine SmPC) |
| Valproate | Aspirin (analgesic doses) | Displaces Valproate from protein binding — increases free (active) Valproate and risk of toxicity. Also additive antiplatelet effect raising bleeding risk. | Avoid high-dose Aspirin in patients on Valproate. Use Paracetamol for analgesia. (BNF) |
Metoclopramide
| Drug A | Drug B | Interaction & Mechanism | Action |
|---|---|---|---|
| Metoclopramide | Antipsychotics (Haloperidol, Prochlorperazine) |
Additive dopamine antagonism — increased risk of extrapyramidal side effects (acute dystonia, akathisia, parkinsonism) and tardive dyskinesia with prolonged use. | Avoid combination where possible. Limit Metoclopramide to short-term use only (MHRA 2014: max 5 days). (BNF · MHRA 2014) |
| Metoclopramide | Opioids | Pharmacodynamic antagonism — Opioids delay gastric emptying; Metoclopramide increases it. Effects partially cancel — Metoclopramide less effective as prokinetic in opioid-treated patients. | Domperidone may be a better antiemetic choice in patients on regular opioids — acts peripherally on gut without opioid antagonism. (BNF) |
Clinical Tools
Interactive scoring tools and checklists for point-of-care use
Migraine Disability Assessment (MIDAS) Score
Validated 5-question tool measuring headache-related disability over the past 3 months. NICE CG150 recommends offering prophylaxis when MIDAS grade ≥ II (score ≥6) combined with ≥4 headache days/month, or MIDAS grade ≥ III (score ≥11) regardless of frequency.
days
days
days
days
days
days
/ 10
Source: Stewart WF et al. Neurology 2000;56:S20–S28. MIDAS questionnaire © Innovative Medical Research 1997. Reproduced for NHS clinical decision support use.
MIDAS Grade Reference
| Grade | Score | Disability Level | Clinical Action (NICE CG150) |
|---|---|---|---|
| I | 0–5 | Little or no disability | Reassurance. Simple analgesics. Lifestyle advice. Review if frequency increases. |
| II | 6–10 | Mild disability | Optimise acute treatment. Consider prophylaxis if ≥4 headache days/month. |
| III | 11–20 | Moderate disability | Offer prophylaxis. Review acute treatment adequacy. Screen for Medication Overuse Headache (MOH). |
| IV | ≥21 | Severe disability | Offer prophylaxis urgently. Consider neurology referral. Assess for Medication Overuse Headache (MOH). Explore impact on employment and daily living. |
Headache Impact Test (HIT-6)
Six-question validated tool assessing the impact of headache on daily life over the past 4 weeks. Quicker than MIDAS; useful for monitoring response to prophylaxis over time. Each question scored: Never (6) · Rarely (8) · Sometimes (10) · Very often (11) · Always (13).
Source: Kosinski M et al. Qual Life Res 2003;12:963–974. HIT-6™ © QualityMetric Inc. Reproduced for NHS clinical decision support use.
HIT-6 Score Reference
| Score Range | Impact Level | Clinical Action |
|---|---|---|
| ≤49 | Little or no impact | Reassurance. Reassess in 3–6 months or if pattern changes. |
| 50–55 | Some impact | Optimise acute treatment. Review trigger management. |
| 56–59 | Substantial impact | Consider prophylaxis. Screen for Medication Overuse Headache (MOH). |
| ≥60 | Severe impact | Offer prophylaxis. Consider neurology referral if not responding to two preventatives. |
Use HIT-6 at baseline and every 3–6 months to monitor treatment response. A reduction of ≥5 points is considered clinically meaningful.
Cluster Headache — Home Oxygen HOOF Checklist
High-flow oxygen is an effective acute treatment for Cluster Headache (~70% response rate) but requires a specialist-initiated Home Oxygen Order Form (HOOF) in NHS. This checklist guides the primary care referral letter to Neurology to ensure all information needed to expedite home oxygen is included.
Before Referring — Confirm Diagnosis Criteria Met
Home Oxygen Order Form (HOOF) — Key Information Neurology Will Need
The Home Oxygen Order Form (HOOF) is completed by the specialist (Neurology), not primary care. However, your referral letter should provide all the clinical data needed for them to complete it promptly. Use the referral template in the Referral Templates tab to pre-populate a Cluster Headache neurology letter.
| HOOF Field | What to Include in Referral |
|---|---|
| Diagnosis | Confirmed or strongly suspected Cluster Headache (International Classification of Headache Disorders (ICHD-3) criteria met — document features) |
| Attack frequency | Number of attacks per day, duration of each attack, current cluster period duration |
| Acute agents tried | Sumatriptan SC — prescribed? Effective? Dose used? |
| O₂ flow rate needed | Standard: 100% O₂ at 12–15 L/min for 15–20 minutes via non-rebreathe mask. State this explicitly. |
| Home circumstances | Confirm patient lives at home (not care home — different pathway); confirm no smoking in household (oxygen fire risk — absolute safety requirement) |
| Contraindications | No contraindication to high-flow oxygen: no Type 2 respiratory failure / Chronic Obstructive Pulmonary Disease (COPD) with CO₂ retention — document if spirometry / blood gases available |
Acute Oxygen Protocol (To Advise Patient Pending Home Supply)
Sit upright or lean forward — supine position reduces efficacy
Apply non-rebreathe mask correctly — ensure valve is patent
Start at 12–15 L/min; maintain for up to 20 minutes
If no improvement after 20 minutes, discontinue — response is usually within 10–15 minutes if effective
Can be used at each attack — no restriction on frequency unlike triptans
Sumatriptan 6 mg subcutaneous (SC) can be used concurrently for faster onset if available
Verapamil Titration — Monitoring Checklist
Verapamil is initiated and titrated by Neurology. This checklist is for primary care awareness when monitoring a patient established on verapamil by a specialist.
| Dose Stage | Electrocardiogram (ECG) Required? | What to Look For |
|---|---|---|
| Before initiation | Yes — baseline | PR interval, QRS width, bradycardia, pre-existing conduction disease |
| Each dose increment | Yes — at each step | PR prolongation (>200 ms), 2nd or 3rd degree heart block, symptomatic bradycardia (<50 bpm) |
| Maintenance | 6-monthly | Ongoing PR monitoring; check for constipation, ankle oedema, fatigue |
| If symptomatic | Same day — urgent | Palpitations, syncope, severe bradycardia → hold dose, urgent cardiological review |
Never co-prescribe Verapamil with Propranolol or other beta-blockers — risk of complete heart block and cardiovascular collapse. (BASH 2023 · BNF)
Referral Templates
Interactive templates — complete fields, then print or copy into your clinical system
Neurology Referral — Migraine / Chronic Headache
Complete all fields. Click Generate Letter to produce a formatted referral. Use Print Letter to print or save as PDF.
Patient Details
Headache History
Acute Treatments Tried
Preventative Treatments Tried (list all — neurology need this)
Safety & Red Flags
Referral Details
Neurology Referral — Cluster Headache (with Home Oxygen Request)
Includes specific language requesting home oxygen initiation (HOOF pathway) and verapamil titration. Fill all fields for a complete referral.
Patient Details
Cluster Headache Features
Treatments Tried
Safety & Referral
Neurology Referral — New Daily Persistent Headache (NDPH) / Atypical Headache
For headache syndromes that do not fit standard primary diagnoses, are refractory, or where secondary pathology must be excluded.
Patient Details
Headache Features
Red Flag Assessment
Neurology Referral — Trigeminal Neuralgia (TN)
Requesting Magnetic Resonance Imaging (MRI) to exclude Multiple Sclerosis (MS), vascular compression, and other structural causes. Includes carbamazepine initiation status.
Patient Details
Trigeminal Neuralgia Features
Treatment & Safety
Patient Resources — Accredited Information Links
NHS · Migraine Trust · OUCH UK · Versus Arthritis · Headache diary apps — for signposting to patients
Curated links to accredited patient-facing information sources. All content is maintained by the source organisation — no patient information is hosted by SynaptAI. Use the filter to find resources by condition, then use Copy Link to paste into a clinical letter, AccuMail message, or text.
💡 Headache diary — recommend at every consultation.
NICE CG150 and BASH 2023 both recommend patients keep a headache diary before and during prophylaxis to monitor headache day frequency, identify triggers, and measure treatment response. Migraine Buddy and N1-Headache are the highest-rated ORCHA-reviewed options. Recommend one of these when starting any preventative treatment.
Clinical Decision Support Only. This tool is intended for use by qualified healthcare professionals registered with an appropriate regulatory body in the United Kingdom (UK). It does not replace clinical judgement or individual patient assessment. All prescribing decisions must be verified against the British National Formulary (BNF), local formulary, and current National Health Service (NHS) guidance. Doses and guidance may change — always check current sources before prescribing. SynaptAI Limited accepts no liability for clinical decisions made using this tool.