Headache & Migraine — micro-course
A free, postgraduate-level taster of the Headache & Migraine CAS. Work the micro-course, then complete the synoptic to earn a downloadable, personalised CPD certificate.
Reviewed and kept current
Last editorial review: 6 June 2026 · Next scheduled refresh: 1 September 2026.
Headache is the second-leading cause of years lived with disability worldwide — and one of the most under-treated
The 2024 Global Burden of Disease analysis ranks migraine as the leading cause of disability in adults under 50 globally and the second cause of disability across all ages. In UK primary care, headache is the third commonest reason for general-practice consultation. Yet the gap between what is now possible — with stratified acute care, CGRP-pathway preventives, MOH detoxification pathways, and emerging neuromodulation — and what most patients actually receive, remains striking. This module is a compressed CAS-level tour designed to close that gap.
What changed. Three convergent pieces of guidance have re-defined headache management this decade: NICE NG150 (Headaches in over-12s) provides the UK pathway; BASH guidance details acute and preventive management for primary-care prescribers; the 2025 IHS-Italian Society joint evidence-based pharmacological guidelines (Ornello, Cephalalgia 2025) and the IHS Global Practice Recommendations (Puledda, Cephalalgia 2024 / 2025) place CGRP-pathway agents formally as first-line preventive options. Add the AHS 2024 CGRP-first position statement and the discipline now has the evidence base its scale of disability burden has long deserved.
Learning objectives — by the end of this micro-course you will be able to
How this maps to the CAS
This taster previews the clinical strands of the Headache & Migraine Certificate of Advanced Studies (CAS) — a standalone FHEQ Level 7 award of 20 UK credits / 10 ECTS (200 notional hours), delivered as a 10-week online cohort and awarded by New Vision University (Tbilisi, Georgia). The strands below are taught as one connected programme within the single CAS, not as separate qualifications.
Diagnosis & Classification
ICHD-3 classification system; primary versus secondary headache; SNNOOP10 red flags; differentiation of migraine, tension-type, cluster, paroxysmal hemicrania, hemicrania continua, SUNCT/SUNA, trigeminal neuralgia, and the secondary-headache prevalences (raised ICP, GCA, SAH, IIH); the place of imaging.
Acute Management & CGRP-era pharmacology
NICE NG150 stratified acute care; even-handed UK triptan portfolio; the gepant acute options (rimegepant, ubrogepant, intranasal zavegepant); the ditan class (lasmiditan); cluster acute care with 100% O₂ pathway; triptan contraindications; pregnancy and CV-risk acute pathways.
Preventive Management & CGRP Monoclonals
NICE NG150 staggered preventive ladder; beta-blockers, candesartan, topiramate, amitriptyline, sodium valproate (with pregnancy prevention programme); botulinum toxin TA260; the four CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab); the gepant preventives (atogepant, rimegepant); 50%-response stop-rule.
MOH, Special Populations & Pipeline
Medication overuse headache — ICHD-3 thresholds, detox strategies, eptinezumab DELIVER 2024 evidence; pregnancy and lactation; paediatric; perimenopausal (BMS 2022 aura position); cardiovascular comorbidity; pipeline (PACAP antibodies, BHV-2100, neuromodulation devices, the PFO-closure debate).
The trigeminovascular system, CGRP, PACAP, and why migraine is a brain condition
For seventy years migraine was framed as a vascular disease — Wolff’s vasodilation hypothesis. The contemporary model, established by Goadsby, Edvinsson, Olesen and Moskowitz across the 1980s–2010s, frames migraine as a primary brain disorder: a paroxysmal neuronal hyperexcitability state with consequent activation of the trigeminovascular system. The therapeutic implications are profound. Triptans, gepants, ditans, CGRP monoclonal antibodies and PACAP antibodies all act on this circuit at different levels.
Mind map — the trigeminovascular system
Eight nodes of the trigeminovascular circuit. CGRP is released from trigeminal-ganglion C-fibres and dural arteries; PACAP shows parallel release; 5-HT(1B/1D/1F) and CGRP receptors are the targets of acute and preventive pharmacology.
Where each drug class acts
| Drug class | Mechanism · target | Primary site of effect |
|---|---|---|
| Triptans (sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan, frovatriptan) | 5-HT1B/1D agonist · pre-synaptic inhibition of CGRP release | Trigeminal ganglion + cranial vasculature; central effect contested |
| Ditans (lasmiditan) | 5-HT1F agonist (no vasoconstriction) | Central trigeminal nucleus; bypasses vasoconstriction |
| Gepants (rimegepant, ubrogepant, atogepant, zavegepant) | Small-molecule CGRP-receptor antagonist | Peripheral and central CGRP receptor |
| CGRP monoclonal antibodies — receptor (erenumab) | Anti-CGRP-receptor antibody | Peripheral receptor blockade; large molecule, no CNS penetrance |
| CGRP monoclonal antibodies — ligand (fremanezumab, galcanezumab, eptinezumab) | Anti-CGRP-ligand antibody | Peripheral binding of free CGRP |
| Botulinum toxin A (TA260, chronic migraine only) | Cleaves SNAP-25; reduces neuropeptide and neurotransmitter release | Peripheral pericranial nerves; PREEMPT 1 / 2 protocol — 31 sites, 155–195 units |
| Beta-blockers (propranolol, metoprolol, bisoprolol) | β-adrenergic antagonism; multiple proposed mechanisms (cortical excitability, brainstem) | Central + peripheral; mechanism not fully understood |
| Candesartan | AT1-receptor antagonist; effect independent of BP-lowering | Off-licence in NICE NG150; useful where beta-blocker contraindicated |
| Topiramate | Multimodal — Na⁺ channel blockade, GABA modulation, glutamate inhibition, carbonic anhydrase inhibition | Cortical excitability; well-tolerated up to 100 mg/day |
| Amitriptyline | Tricyclic — 5-HT and NA reuptake inhibition; multiple analgesic mechanisms | Particularly useful where insomnia or co-existing tension-type headache |
| PACAP antibodies (Lu AG09222 — phase 2 positive 2024) | Anti-PACAP monoclonal antibody; parallel pathway to CGRP | Peripheral PACAP-38; emerging preventive class |
Translational pearl. CGRP is necessary but not sufficient for migraine. Phase 2 PACAP-antibody trials (Lu AG09222) demonstrating efficacy in patients refractory to CGRP-pathway agents establish PACAP as the first viable second-pathway target. Goadsby (Lancet 2025) frames the future of migraine prevention as “very bright” given CGRP-PACAP pathway synergy and emerging targets including amylin, adrenomedullin, and ATP-sensitive potassium channels.
The diagnostic framework that anchors everything else
The International Classification of Headache Disorders, third edition (ICHD-3, 2018; ongoing online updates) is the canonical diagnostic framework for headache. It distinguishes primary headaches (migraine §1, tension-type §2, trigeminal autonomic cephalalgias §3, other primary §4) from secondary headaches (§5–§14) and the painful cranial neuropathies and other facial pains (§13). Every formal NICE NG150, BASH and IHS recommendation is anchored to ICHD-3 codes.
The primary headaches at a glance
| ICHD-3 code · entity | Defining clinical features | UK prevalence · M:F · primary-care relevance |
|---|---|---|
| §1.1 Migraine without aura | ≥ 5 attacks; 4–72 h untreated; ≥ 2 of (unilateral, pulsating, moderate-severe, aggravation by movement); ≥ 1 of (nausea/vomiting, photo-/phonophobia) | ~ 12% UK adults; F:M 3:1; commonest disabling primary headache. |
| §1.2 Migraine with aura | Migraine with reversible focal neurological aura — visual (commonest), sensory, speech, motor; typically < 60 min, then headache | ~ 2% UK adults; consider FH stroke, OCP / oral HRT contraindication, FSRH UKMEC. |
| §1.3 Chronic migraine | Headache ≥ 15 days/month for ≥ 3 months, of which ≥ 8 days are migrainous | ~ 2% of UK adults; majority have MOH overlay; preventive therapy mandatory. |
| §1.5 Hemiplegic migraine (familial / sporadic) | Migraine with motor weakness; familial = AD with CACNA1A, ATP1A2, SCN1A mutations | Specialist referral; triptans contraindicated; gepants are now the safer acute option. |
| §1.6.6 Vestibular migraine (Bárány Society 2012) | Vestibular symptoms (vertigo, motion sensitivity) ≥ 5 episodes; concurrent migrainous features | ~ 1% UK adults; under-recognised; treats well with migraine preventives. |
| §2 Tension-type headache | Bilateral, pressing/tight, mild-moderate, no aggravation by movement, no/mild nausea | ~ 40% UK adults; least disabling but most prevalent. |
| §3.1 Cluster headache | Severe unilateral orbital/supraorbital, 15–180 min, 1–8/day during bout, ipsilateral autonomic features (lacrimation, ptosis, miosis, rhinorrhoea, agitation) | ~ 0.1% UK adults; M:F 3:1; circadian / circannual periodicity; NICE NG150 + BASH 2019 / 2024. |
| §3.2 Paroxysmal hemicrania | Severe unilateral, 2–30 min, 5–40/day, ipsilateral autonomic features; indomethacin-responsive | Rare; differentiate from cluster by duration and frequency; indomethacin trial diagnostic. |
| §3.3 SUNCT / §3.4 SUNA | Brief unilateral neuralgiform 1–600 sec, very high frequency, autonomic features | Rare; specialist; lamotrigine first-line; trigeminal nerve imaging mandatory. |
| §4.10 Hemicrania continua | Continuous unilateral headache with periodic exacerbations and ipsilateral autonomic features; indomethacin-responsive | Often misdiagnosed as chronic migraine; indomethacin trial diagnostic. |
The indomethacin pearl. Two ICHD-3 diagnoses respond exclusively to indomethacin: paroxysmal hemicrania (§3.2) and hemicrania continua (§4.10). Both are commonly misdiagnosed as chronic migraine or cluster, and both transform with a structured indomethacin trial — typically 25 mg three times daily titrating to 50 mg three times daily over 1–2 weeks, with a PPI for gastric protection. A complete or near-complete response is diagnostic. Without indomethacin, these patients are consigned to ineffective preventive ladders.
High-yield secondary headaches in primary care
Secondary headaches make up about 5–10% of headache presentations in primary care but disproportionately drive the safety teaching. The four most consequential to recognise are subarachnoid haemorrhage, giant cell arteritis, idiopathic intracranial hypertension, and meningitis / encephalitis. Each has a distinct pattern; each has a distinct pathway.
| Secondary headache | Recognition pattern | UK pathway |
|---|---|---|
| Subarachnoid haemorrhage | Thunderclap onset, peak intensity within seconds; the “worst-ever” headache; often with neck stiffness, photophobia, transient LOC, focal signs | Same-day acute medical / emergency department; CT head within 6 h has > 99% sensitivity; LP at 12 h if CT negative. |
| Giant cell arteritis | ≥ 50 years, new-onset headache, scalp tenderness, jaw claudication, visual disturbance, polymyalgia features; ESR/CRP raised | Start prednisolone 60 mg same day if visual symptoms; urgent rheumatology / temporal artery biopsy within 1 week; NICE NG150 / BSR. |
| Idiopathic intracranial hypertension (IIH) | Young, female, BMI ≥ 30; daily progressive headache, papilloedema, transient visual obscurations, pulsatile tinnitus | Urgent ophthalmology / neurology; LP with opening pressure > 25 cm CSF; weight reduction + acetazolamide; surgical CSF shunt or stenting if vision-threatening. |
| Meningitis / encephalitis | Fever, neck stiffness, photophobia, altered consciousness, rash; sub-acute progression in TB / fungal causes | Same-day emergency; empirical antibiotics ± aciclovir before LP if delay anticipated; NICE NG240 (community-acquired meningitis). |
The triage framework that should run silently in every headache consultation
The SNNOOP10 mnemonic (Do et al, Neurology 2019) is the contemporary international consensus screen for secondary headache. Each letter represents a high-yield clinical or contextual feature. The framework runs silently in every primary-care headache consultation; a positive flag triggers escalation along the appropriate pathway.
The SNNOOP10 decision flowchart
SNNOOP10 (Do et al, Neurology 2019) is the consensus screen for secondary headache. The 1-of-10 threshold is intentionally low because the consequences of missing a secondary headache are severe and the consequences of one extra imaging investigation are mild.
Six high-impact safety pearls.
NICE NG150 stratified care — match the agent to the attack severity, not to the historical ladder
The single most important shift in NICE NG150 was the move from a stepwise care model (try simple analgesics first, escalate only on failure) to stratified care — selecting the acute therapy based on the severity and disability of the typical attack from the first consultation. The IHS Global Practice Recommendations (Puledda 2024) and the 2025 IHS-Italian Society guideline (Ornello, Cephalalgia 2025) endorse the same principle: a patient with severe disabling migraine should not be required to fail paracetamol before being offered a triptan or gepant.
The acute migraine ladder
Mild attacks · simple analgesics ± antiemetic
Aspirin 900 mg, ibuprofen 400–600 mg, naproxen 500–1000 mg, or paracetamol 1 g — always combined with an antiemetic (metoclopramide 10 mg or prochlorperazine 10 mg) which both treats nausea and accelerates absorption. Effervescent / soluble formulations preferred for gastric absorption during attack.
Moderate-severe attacks · triptan ± NSAID
Triptan first-line. Sumatriptan 50–100 mg orally, 6 mg subcutaneous (fastest onset), 10–20 mg nasal (option for vomiting); rizatriptan 10 mg; zolmitriptan 2.5–5 mg oral or 5 mg nasal; eletriptan 40–80 mg; naratriptan 2.5 mg (slower onset, longer half-life — useful for menstrual migraine prevention); almotriptan 12.5 mg; frovatriptan 2.5 mg. Combine with NSAID for additive effect (Sumatriptan-naproxen — Treximet — combination evidence base). Take at the onset of pain; do not wait for it to escalate.
Triptan-failure or triptan-contraindicated · gepants
Rimegepant 75 mg orally as needed (also licensed preventive every other day); ubrogepant 50–100 mg orally as needed. Zavegepant 10 mg intranasal where available — fastest gepant onset. Gepants do not cause vasoconstriction so are safe in established CV disease, prior MI, stroke, uncontrolled hypertension, pregnancy considerations — exactly where triptans are contraindicated. NICE TA919 (rimegepant), TA973 (ubrogepant), TA1132 (zavegepant nasal where applicable).
Status migrainosus / refractory acute attack
≥ 72 hours continuous severe migraine. Ladder: oral triptan + NSAID + antiemetic; subcutaneous sumatriptan; IV / IM diclofenac (depending on local protocol); IV metoclopramide; greater occipital nerve block. Steroid taper (prednisolone 60 mg tapering over 6 days) for status migrainosus is BASH-supported. Avoid opioid; avoid pethidine.
What NOT to use
Codeine and other opioids — high MOH risk, low efficacy. Combination paracetamol + codeine (co-codamol) is a particular trap. Pethidine (FY-prescribed in past) is contraindicated. Ergotamines are obsolete in UK practice given triptan and gepant availability.
Even-handed UK triptan portfolio
| Agent · routes | Onset · half-life · features | Position |
|---|---|---|
| Sumatriptan (oral, SC, intranasal) | Onset 10 min SC / 30 min PO; t½ 2 h | First-line UK triptan. SC fastest onset for severe attacks; PO 50 mg first try. |
| Rizatriptan (oral, oral wafer) | Onset 30 min; t½ 2–3 h | Higher 2-h pain-free rate than sumatriptan in head-to-head trials; reduce to 5 mg if on propranolol. |
| Zolmitriptan (oral, oral wafer, intranasal) | Onset 30 min; nasal < 15 min; t½ 3 h | Nasal route useful for nausea / vomiting; first-line in cluster headache (NICE NG150). |
| Eletriptan (oral) | Onset 30 min; t½ 4 h | Highest efficacy in head-to-head; relative CYP3A4 caution. |
| Naratriptan (oral) | Onset slower 1–2 h; t½ 6 h (longest) | Slower onset, longer effect — useful for menstrual migraine mini-prophylaxis; lower headache recurrence. |
| Almotriptan (oral) | Onset 30 min; t½ 3.5 h | Better-tolerated than sumatriptan; option for triptan-naive moderate attacks. |
| Frovatriptan (oral) | Onset slower; t½ 26 h (very long) | Niche in menstrual mini-prophylaxis (ICHD-3 §A1.1.1); rarely used acute. |
The triptan switch pearl. A patient who fails one triptan has a 30–40% chance of responding to a second triptan from a different class. Trial three different triptans across different attacks before declaring “triptan-resistant”. Combine with NSAID and antiemetic for additive effect. Take at onset of pain (not at aura). Limit to ≤ 10 days per month to prevent MOH.
The gepant acute portfolio
| Agent · route | Acute dose · NICE position | Notable features |
|---|---|---|
| Rimegepant (oral, ODT — orally disintegrating) | 75 mg as needed (max one dose per 24 h); NICE TA919 (acute) and approved preventive at 75 mg every other day | Dual indication acute + preventive (the only gepant licensed for both in UK). 2-h pain-free response ~ 20% vs ~ 11% placebo (NEJM 2019). |
| Ubrogepant (oral) | 50 mg or 100 mg as needed (max 200 mg per 24 h); NICE TA973 | Established acute efficacy; 2-h pain-free 22% vs 14% placebo (NEJM 2019). TANDEM trial (2025) demonstrates safe co-prescription with daily atogepant. |
| Zavegepant (intranasal) | 10 mg intranasal as needed; NICE TA1132 / equivalent | Fastest-acting gepant — 2-h pain-free benefit at 15 minutes; useful where vomiting precludes oral; intranasal formulation only. |
| Lasmiditan (oral · ditan class) | 50 / 100 / 200 mg as needed; NICE TA discontinued 2022 — not currently NICE-positive in UK | 5-HT1F agonist without vasoconstriction; option in CV-comorbid patients in jurisdictions where licensed; sedation and driving caution. |
Triptan contraindications — the safety repertoire
Embedded knowledge check — acute migraine
Mini-SBA · 36-year-old woman with severe migraine and recent MI
A 36-year-old woman with migraine without aura presents requesting acute treatment. She had an unprovoked NSTEMI 4 months ago (cardiology workup negative for atherosclerosis; presumed coronary spasm) and is now on aspirin 75 mg, ticagrelor 90 mg twice daily, atorvastatin 80 mg, ramipril 5 mg, and bisoprolol 2.5 mg. Migraine attacks 2–3 per month, each lasting 24–36 hours, severe with vomiting. NSAIDs partially effective. BP 122/76. ECG normal sinus rhythm. What is the most appropriate acute therapy?
Correct answer: C. Triptans (A, B) are absolutely contraindicated in established ASCVD including prior MI — irrespective of the underlying mechanism (atherosclerotic vs vasospastic). Gepants do not cause vasoconstriction and are the contemporary first-line acute therapy in this exact scenario. Rimegepant 75 mg ODT is NICE TA919-approved and convenient when nausea is present (orally-disintegrating). Ubrogepant or intranasal zavegepant would also be reasonable. Codeine-containing opioids (D) carry high MOH risk and minimal evidence of efficacy. Ergotamines (E) are obsolete in UK practice and contraindicated in CV disease. The 2025 IHS-Italian Society guideline and AHS 2024 position both endorse gepants for cardiovascular-comorbid migraine.
The NICE NG150 staggered ladder, even-handedly applied
NICE NG150 recommends preventive therapy for any patient with ≥ 4 migraine days per month or substantial disability at lower frequency. The historic preventive ladder — propranolol → topiramate → amitriptyline → sodium valproate → onward — has been substantially reshaped by the CGRP era. The 2025 IHS-Italian Society guideline grades CGRP-pathway preventives as the highest-evidence preventive class. NICE TAs now permit use of CGRP mAbs and gepants after failure of three traditional preventives in episodic migraine, or after failure of three traditional preventives plus botulinum toxin in chronic migraine.
The contemporary preventive ladder
Beta-blocker · candesartan · amitriptyline · topiramate (any one as first-line)
NICE NG150 lists propranolol (40–160 mg/day) and topiramate (50–100 mg/day) as first-line. BASH adds candesartan (8–16 mg/day, off-licence but well-evidenced) and amitriptyline (10–75 mg nocte) as alternatives, particularly where co-existing hypertension (candesartan), insomnia or co-existing tension-type headache (amitriptyline), or where weight gain on beta-blocker is undesirable (topiramate often causes weight loss). Trial each at adequate dose for 8–12 weeks before declaring failure.
Sodium valproate (with the Pregnancy Prevention Programme)
500–1500 mg/day. Contraindicated in women of childbearing potential without enrolment in the MHRA Pregnancy Prevention Programme — bear this in mind for any woman with migraine where preventive escalation is contemplated. Effective; use second- or third-line where the PPP issue is moot (men, post-menopause, established contraception).
Riboflavin 400 mg / coenzyme Q10 / magnesium / feverfew (mid-line evidence)
Riboflavin 400 mg/day has the best evidence among nutritional preventives — meta-analytic effect size moderate. Patients reasonably ask about nutraceuticals; offer rather than dismiss. Avoid feverfew in pregnancy; magnesium oxide / glycinate 300–600 mg/day reasonable adjunct.
Botulinum toxin A · NICE TA260 (chronic migraine only)
For chronic migraine only (≥ 15 headache days/month, ≥ 8 of which migrainous, for ≥ 3 months) failing ≥ 3 preventives. PREEMPT 1 / 2 protocol — 31 sites, 155–195 units onabotulinumtoxinA, every 12 weeks. Specialist neurology / specialist headache nurse delivery.
CGRP-pathway preventives — the contemporary fifth-line
NICE-permitted after three traditional preventive failures (episodic migraine) or three traditional + botulinum failure (chronic migraine). Erenumab, fremanezumab, galcanezumab, eptinezumab (mAbs); atogepant, rimegepant (gepant preventives). Detailed in Section 07.
The 50%-response stop-rule and de-prescribing
NICE preventive stop-rules. Across all preventive agents, NICE NG150 recommends discontinuation if there is no clinically meaningful response after an adequate trial — typically 8–12 weeks at therapeutic dose. For CGRP mAbs and gepants, NICE TA wording is more specific: continue only if monthly migraine days reduce by ≥ 50% in episodic migraine, or by ≥ 30% in chronic migraine, after the licensed assessment period (typically 12 weeks for mAbs, 12 weeks for atogepant, 24 weeks for fremanezumab quarterly dosing). After 12 months of clinically meaningful response, consider a planned trial off therapy to reassess underlying disease activity.
Embedded knowledge check — preventive ladder
Mini-SBA · 28-year-old woman with episodic migraine wanting preventive therapy
A 28-year-old woman has 6 migraine days per month, each lasting 12–18 hours, mostly responsive to sumatriptan 50 mg + ibuprofen. She is not currently using contraception, is not pregnant, but has a long-term partner and has not finalised plans about pregnancy. BMI 22, BP 116/74, mood normal. Which preventive option is most appropriate first-line, per NICE NG150?
Correct answer: A. Beta-blocker (propranolol) is first-line preventive in NICE NG150 alongside topiramate; in a woman of childbearing potential without contraception, propranolol is preferable to topiramate because (a) topiramate reduces the efficacy of combined hormonal contraception, complicating future contraceptive choices, and (b) topiramate is teratogenic (cleft lip/palate, hypospadias) and so requires explicit pre-conception counselling and PPP-style contraception. Sodium valproate (C) is contraindicated in women of childbearing potential without PPP enrolment and is therefore ruled out here. CGRP-pathway preventives (D, E) are NICE-positive only after failure of three traditional preventives in episodic migraine; she has not yet trialed any traditional agent.
The first targeted preventive class for migraine — and the clearest demonstration of mechanism-led drug development since the triptans
The CGRP-pathway therapeutics — four monoclonal antibodies plus four gepants — were developed from the discovery that calcitonin gene-related peptide is the dominant neuropeptide released during a migraine attack. Both classes are mechanistically targeted; both classes have demonstrated efficacy in episodic and chronic migraine; the mAbs have additional evidence in cluster headache and MOH. The 2024 American Headache Society position statement and the 2025 IHS-Italian Society guideline grade CGRP-pathway agents as the highest-evidence preventive class.
Even-handed UK CGRP-pathway portfolio
| Agent | Mechanism · route · dose | NICE TA · indication · stop rule |
|---|---|---|
| Erenumab (Aimovig) | Anti-CGRP-receptor mAb · SC monthly · 70 mg or 140 mg | NICE TA682 — episodic and chronic migraine after 3 preventive failures (episodic) or 3 preventives + botulinum failure (chronic). Stop if < 50% reduction (episodic) or < 30% (chronic) at 12 weeks. |
| Fremanezumab (Ajovy) | Anti-CGRP-ligand mAb · SC monthly 225 mg or quarterly 675 mg | NICE TA631 — same indications and stop rule as erenumab; quarterly dosing is a major adherence advantage. |
| Galcanezumab (Emgality) | Anti-CGRP-ligand mAb · SC monthly 240 mg loading then 120 mg | NICE TA659 — same indications. Also NICE TA855 in episodic cluster headache at 300 mg monthly. |
| Eptinezumab (Vyepti) | Anti-CGRP-ligand mAb · IV every 12 weeks · 100 mg or 300 mg | NICE TA764 — same indications. DELIVER 2024 trial showed efficacy in patients with prior preventive failure including in MOH. |
| Atogepant (Aquipta / Qulipta) | Oral CGRP-receptor antagonist · 60 mg daily · preventive only | NICE TA871 — episodic and chronic migraine after 3 preventives. Once-daily oral. Lower number-needed-to-treat than CGRP mAbs in head-to-head meta-analyses. |
| Rimegepant (Nurtec) | Oral CGRP-receptor antagonist · 75 mg every other day for prevention; 75 mg as needed for acute | NICE TA919 — both acute (in eligible patients) and preventive. Only gepant licensed for both. Useful where intermittent / as-needed preventive use suits the patient pattern. |
| Ubrogepant (Ubrelvy) | Oral CGRP-receptor antagonist · 50–100 mg as needed · acute only | NICE TA973 — acute treatment. TANDEM trial 2025 supports safe co-prescription with daily atogepant. |
| Zavegepant (Zavzpret) | Intranasal CGRP-receptor antagonist · 10 mg as needed · acute only | NICE TA1132 / equivalent — acute treatment. Fastest-onset gepant; useful for nausea / vomiting. |
Translational pearl — the receptor versus ligand distinction. Erenumab is the only UK-licensed mAb that targets the CGRP receptor; fremanezumab, galcanezumab and eptinezumab target the CGRP ligand. The clinical implication is that CGRP-pathway non-responders to one mechanism (e.g. ligand-binding) can reasonably trial the alternative mechanism (receptor-binding), and vice versa. NICE guidance permits this in the post-failure pathway. Constipation is more common with erenumab; injection-site reactions with the ligand-binding mAbs are otherwise comparable.
CGRP-pathway in primary care — the BJGP framework (Wober 2024)
The September 2024 British Journal of General Practice article on CGRP therapy in primary care (Wober et al) synthesises the practical primary-care framework: identify patients who have failed three traditional preventives at adequate dose for adequate duration; refer to specialist headache clinic for CGRP initiation; receive shared-care prescribing arrangements; deliver follow-up monitoring. UK practice for many ICBs is now CGRP initiation in tertiary care with 6–12-month review and primary-care continuation prescribing, although some ICBs operate full primary-care prescribing under shared-care protocols.
Embedded knowledge check — CGRP pathway
Mini-SBA · Chronic migraine with prior CGRP mAb failure
A 42-year-old woman with chronic migraine (~ 22 headache days per month, 12 of which migrainous) has trialed and failed propranolol, topiramate, amitriptyline, and onabotulinumtoxinA at PREEMPT-protocol dose for two cycles. She has had three months of erenumab 140 mg subcutaneous monthly with only a 15% reduction in monthly headache days — does not meet the NICE 30% stop-rule for chronic migraine continuation. What is the most appropriate next step in CGRP-pathway management?
Correct answer: C. Erenumab is the only UK CGRP-receptor antagonist mAb; fremanezumab, galcanezumab and eptinezumab bind the CGRP ligand. Mechanistic non-response to one CGRP-pathway mechanism does not preclude response to the alternative — patients failing one mechanism have a 30–40% chance of responding to the other (per IHS Global Practice Recommendations 2024). NICE permits switching within the CGRP-pathway after non-response, although local commissioning protocols vary. Continuing the same agent (A) wastes resources. Erenumab dose maximum is 140 mg (B). Stopping all preventives (D) ignores the chronic migraine indication. Restarting topiramate (E) duplicates a previous failure.
The non-migraine primary headaches — most common, most distinctive, most under-treated
Tension-type headache is the commonest primary headache; cluster headache is the most severe; the indomethacin-responsive TACs (paroxysmal hemicrania, hemicrania continua) are the most diagnostically transformative. SUNCT/SUNA is the rarest. Trigeminal neuralgia, although classified separately under §13 cranial neuropathies, sits adjacent to the TACs in the differential.
Cluster headache — the acute O₂ pathway
Cluster headache attacks are extreme — described as “suicide headaches”. The therapeutic mainstay is 100% oxygen via non-rebreather mask at 12–15 L/min for 15–20 minutes, which aborts ~ 70% of attacks. NHS provision of home oxygen for cluster patients is a NICE NG150 entitlement.
Acute attack — 100% O₂ at 12–15 L/min via non-rebreather mask for 15–20 min
Most effective acute treatment in cluster — NICE NG150-endorsed, BASH-supported. NHS home-oxygen prescribing form HOOF Part B; arrange via local home-oxygen provider with specialist sign-off. Patients require a portable cylinder for travel.
Sumatriptan 6 mg subcutaneous as second-line acute
SC route only — oral and nasal too slow for typical 15–180 minute attacks. Maximum twice daily. Avoid oral triptans in cluster — the attack typically resolves before oral absorption reaches therapeutic concentration.
Zolmitriptan 5 mg intranasal — alternative to subcutaneous
Patient-acceptability advantage over SC; somewhat slower onset.
Preventive — verapamil 240–960 mg/day with ECG monitoring
First-line preventive. Start at 80 mg three times daily; increase by 80 mg every 1–2 weeks; ECG before each escalation looking for PR-interval prolongation (stop if PR > 220 ms or new bundle branch block).
Preventive bridging — suboccipital steroid injection or oral prednisolone taper
For bout-onset cluster while verapamil titrates; suboccipital methylprednisolone + lidocaine combination provides 1–4 weeks of cover.
Refractory cluster — galcanezumab 300 mg monthly (NICE TA855, episodic only)
Galcanezumab is the first CGRP mAb licensed in episodic cluster (TA855); chronic cluster remains an unmet need for which IHS supports off-licence galcanezumab and other CGRP mAbs after specialist input. Lithium and topiramate are alternative refractory preventives.
The indomethacin-responsive TACs
| Entity (ICHD-3) | Pattern | Diagnostic / therapeutic approach |
|---|---|---|
| Paroxysmal hemicrania (§3.2) | Severe unilateral, 2–30 min, 5–40/day, ipsilateral autonomic features | Indomethacin 25 mg three times daily titrating to 50 mg three times daily over 1–2 weeks; complete or near-complete response is diagnostic. Continue with PPI cover. |
| Hemicrania continua (§4.10) | Continuous unilateral with periodic exacerbations + ipsilateral autonomic features | Same indomethacin trial; response is diagnostic. Often misdiagnosed as chronic migraine — this trial transforms care. |
| SUNCT / SUNA (§3.3 / §3.4) | Brief unilateral neuralgiform 1–600 sec, very high frequency, autonomic features | Lamotrigine first-line (specialist initiation); MRI mandatory to exclude posterior fossa lesion; specialist referral. |
| Trigeminal neuralgia (§13.1) | Brief paroxysmal unilateral facial pain in trigeminal distribution; trigger zones | Carbamazepine first-line (NICE NG150); oxcarbazepine alternative; if refractory — gabapentin / lamotrigine / specialist neurosurgical (microvascular decompression). |
The Goadsby pearl on TAC differentiation. Cluster (15–180 min, 1–8/day), paroxysmal hemicrania (2–30 min, 5–40/day) and SUNCT/SUNA (1–600 sec, very high frequency) form a spectrum of shorter and more frequent. Indomethacin-responsiveness defines paroxysmal hemicrania and hemicrania continua. Not following this taxonomy means patients with PH spend years on cluster regimens. Trial indomethacin in any unilateral autonomic-features headache where the duration / frequency does not match cluster.
Tension-type headache — brief notes
The commonest primary headache; bilateral, pressing, mild-to-moderate, no aggravation by movement, no/mild nausea. NICE NG150 acute management: paracetamol, aspirin, ibuprofen, naproxen. Preventive (frequent episodic or chronic): amitriptyline 10–75 mg nocte (off-licence but well-evidenced); consider acupuncture (NG150 supports a course of up to 10 sessions over 5–8 weeks); CBT for chronic TTH. Limit acute analgesic use to ≤ 15 days/month to prevent MOH transformation.
The most common reversible cause of chronic daily headache
Medication overuse headache (MOH; ICHD-3 §8.2) is the iatrogenic transformation of episodic migraine into chronic daily headache through frequent acute-medication use. ICHD-3 thresholds: simple analgesics (paracetamol, NSAIDs, aspirin) on ≥ 15 days per month for ≥ 3 months; opioids, triptans, ergotamines, or combination analgesics on ≥ 10 days per month for ≥ 3 months. Approximately 50–70% of patients with chronic migraine have an MOH overlay; recognition transforms outcomes.
The MOH detoxification pathway
| Step | Action | Notes |
|---|---|---|
| 1 · Identify and counsel | Headache diary; identify the overused medication; explain MOH paradox (more medication = more headache) | Patient buy-in is essential. Frame as “your headache treatment has stopped working and may be making things worse” rather than as criticism. |
| 2 · Choose detox strategy | (a) Abrupt stop (preferred for simple analgesics, NSAIDs, triptans); (b) gradual taper (preferred for opioids, butalbital, benzodiazepine combinations) | Abrupt cessation is associated with a 2–10 day rebound headache then resolution. BASH and IHS both endorse abrupt for non-opioid medications. |
| 3 · Bridging therapy | Steroid taper (prednisolone 60 mg tapering over 6 days); naproxen 500 mg twice daily for 1–2 weeks; greater occipital nerve block; antiemetic + IV fluid in inpatient setting | Variable evidence; clinical experience supports steroid bridging for 60–70% of patients. Does not work for opioid MOH. |
| 4 · Initiate / optimise preventive therapy | Start a preventive concurrent with detox; CGRP-pathway agents have notable evidence in MOH (see DELIVER 2024 below) | Preventive therapy started during detox improves the chance of long-term success. |
| 5 · Long-term acute prescribing limits | Document “maximum 10 days per month for triptans, 15 for simple analgesics” in record and on patient information | Practice-level template change is the single highest-impact intervention. |
The DELIVER 2024 pearl. The DELIVER trial (Diener, Cephalalgia 2024) randomised 890 patients with chronic migraine and MOH (≥ 8 migraine days/month plus medication overuse) to eptinezumab 100 mg IV every 12 weeks vs placebo. Eptinezumab achieved significantly greater reduction in monthly migraine days without requiring formal detoxification first — challenging the historic teaching that detox must precede preventive initiation. The contemporary IHS position is that CGRP-pathway preventives may be initiated concurrently with — rather than after — MOH detox.
Where the standard headache pathway requires deliberate adaptation
Five populations consistently demand departure from the standard NICE NG150 pathway: pregnancy and lactation, paediatric, the perimenopausal woman with worsening migraine, the patient with established cardiovascular disease, and the older adult with new-onset headache.
Pregnancy & lactation
Acute: paracetamol first-line in all trimesters; sumatriptan SC has the largest dataset and is generally accepted second-line; NSAIDs avoided in third trimester (premature ductus closure). Preventive: propranolol acceptable; amitriptyline acceptable; topiramate, sodium valproate contraindicated; CGRP-pathway agents — limited human data, generally avoided. Lactation: most acute and preventive medications acceptable per LactMed; sodium valproate avoided.
Perimenopausal migraine + aura
BMS 2022 / FSRH joint position: migraine with aura is not a contraindication to transdermal HRT. Aura on combined hormonal contraception is FSRH UKMEC 4 — stop COC. Aura on oral oestrogen-containing HRT — switch to transdermal. Migraine frequency often falls on stable transdermal oestradiol (oestrogen withdrawal is a migraine trigger). Track migraine on a diary; titrate transdermal dose to symptom control.
Cardiovascular comorbid migraine
Established CVD (prior MI, stroke, TIA, PAD) is an absolute contraindication to triptans and ergotamines. Gepants are the contemporary acute therapy in this population — no vasoconstriction. CGRP mAbs do not have clear cardiovascular safety signals at population level; FDA / MHRA labelling notes BP-monitoring in patients with hypertension on erenumab. Migraine with aura is itself a CV risk factor — manage statins, BP, smoking aggressively (ESC 2023).
Paediatric headache
NICE NG150 covers over-12s. Acute: ibuprofen 10 mg/kg or paracetamol; nasal sumatriptan 10–20 mg licensed for ≥ 12 years. Preventive: propranolol or topiramate (specialist). Lifestyle audit (sleep, hydration, screen time, food triggers) usually highest yield. CGRP-pathway agents — emerging paediatric trials; not yet routinely available under 18.
Older-adult new-onset headache. First-onset headache aged > 50 is a SNNOOP10 red flag. Systematic exclusion of giant cell arteritis (ESR / CRP, scalp tenderness, jaw claudication, polymyalgia features), space-occupying lesion (MRI brain), and IIH (papilloedema check) is mandatory before primary-headache diagnosis. New cluster-pattern at this age requires MRI brain regardless of typical features.
What is happening in the field 2026–2028
Three frontiers define the next phase: PACAP-pathway therapeutics as the second mechanistic preventive class beyond CGRP; novel small-molecule and ion-channel approaches (TRPM3, neuropeptide Y); and the maturation of neuromodulation devices into clinically meaningful chronic-migraine options. The PFO-closure question remains critically debated. Goadsby (Lancet 2025) frames the future as “very bright” given the multiple converging targets.
Pipeline at a glance
| Agent / device | Mechanism · trial · status | Anticipated UK arrival |
|---|---|---|
| Lu AG09222 (PACAP-38 mAb) | Anti-PACAP-38 monoclonal antibody · phase 2 positive 2024 · phase 3 ongoing | 2027–28 anticipated EMA / NICE submission |
| BHV-2100 | TRPM3 antagonist · acute migraine · phase 2 positive AAN 2025 | 2028+ if phase 3 positive |
| Atogepant vs topiramate (TEMPLE trial) | Direct head-to-head; 545 patients; readout May 2026 | Will reshape preventive guidance if atogepant superior |
| ShiraTronics implantable neuromodulation | Dual-target occipital + supraorbital implant · RELIEV-CM pilot positive | 2027+ if pivotal trial positive |
| External neuromodulation (Cefaly, Nerivio, gammaCore, sTMS) | Non-invasive devices already FDA-cleared in US; UK adoption variable | UK availability via specialist centres; NICE evaluations ongoing |
| NPY antagonists, amylin pathway, ATP-sensitive K-channel modulators | Early-stage discovery | Long-term horizon (2030+) |
| PFO closure for migraine with aura | PRIMA, PREMIUM, MIST trials negative on primary endpoints; observational benefit in selected aura subgroup | Not currently NICE-positive; specialist consideration for refractory aura with bubble study + PFO confirmed |
| Anti-CGRP-receptor antagonist for cluster (galcanezumab) | NICE TA855 — episodic cluster only. Chronic cluster remains an unmet need | Already UK-available episodic; chronic indication awaited |
Expert voices on the future of migraine therapy
Quotations kept under fifteen verbatim words per source for academic-fair-use compliance.
On the CGRP era
Goadsby (Lancet 2025) frames the field — “the future of the prevention of migraine is very bright” — given converging CGRP-PACAP synergies and emerging neuropeptide targets. The CAS reading: the pipeline is the deepest in any neurology subspecialty and CGRP-pathway agents are the start, not the end.
On preventive therapy
Silberstein (AHS 2024 position statement) summarises CGRP-pathway agents as “first-line preventive treatment” in episodic migraine — a major guideline shift. The CAS reading: CGRP mAbs and gepants no longer require failure of three traditional preventives in some jurisdictions; UK NICE wording is more conservative.
On MOH
Diener (Cephalalgia 2024 DELIVER) demonstrated that “eptinezumab significantly reduced” monthly migraine days in chronic migraine plus MOH without prior detox. The CAS reading: the historic detox-first sequence is becoming detox-with-preventive in CGRP-era practice.
On migraine in women
MacGregor (BMS 2022 / Headache 2024) led the joint position that “transdermal HRT is not contraindicated” in migraine with aura — overturning a generation of restrictive practice. The CAS reading: aura on transdermal route is acceptable; aura on COC or oral HRT is not.
On paediatric migraine
Hershey (Headache 2026 paediatric pipeline review) frames paediatric headache as a population “in unmet need” awaiting the CGRP-era trials. The CAS reading: emerging paediatric atogepant and rimegepant data may change UK practice 2027+.
On UK headache services
Ahmed (BASH chair) emphasises the gap between “available evidence” and UK service capacity; many ICBs lack a tertiary headache service to deliver the CGRP-pathway therapeutic transformation. The CAS reading: GPwER headache pathways are now part of the NHS solution.
The CAS framing of the future. If the 2010s gave us the triptan paradigm consolidated, the 2020s have given us the CGRP-pathway first-line preventive era. The 2026–2030 window will be defined by (a) PACAP-pathway therapeutics arriving as the second targeted mechanism, (b) gepants (atogepant in particular) potentially overtaking triptans and beta-blockers as the primary-care default, (c) implantable and non-invasive neuromodulation maturing, and (d) the long-debated PFO-migraine question reaching a settled position. Plan your headache service capacity, your GPwER pathways, and your CPD around this calendar.
Vygotsky-style challenge — patients who would be discussed at a specialist headache MDT
Three cases sit deliberately above MRCGP-AKT difficulty in the spirit of Vygotsky's zone of proximal development — challenging the trainee just beyond comfortable competence with structured scaffolding via staged Socratic accordions. Each requires synthesis across at least two of the four CAS units and at least two guideline frameworks.
54-year-old woman with refractory chronic migraine and complex comorbidity
A 54-year-old social worker has chronic migraine for 15 years (currently 24 headache days/month, 14 of which migrainous). She had an unprovoked NSTEMI 18 months ago and is on aspirin, ticagrelor (recently completed 12 months and now stopped), atorvastatin 80 mg, ramipril, bisoprolol. She uses sumatriptan 50 mg on 18 days per month plus co-codamol 30/500 mg three to four tablets daily — clear medication overuse. Failed: propranolol (hypotension), topiramate (paraesthesia and word-finding difficulty), amitriptyline (sedation), sodium valproate (declined — childbearing potential historically). Two cycles of botulinum toxin produced 20% reduction. PHQ-9 14, GAD-7 12. Build her plan.
Q1 · How do you sequence MOH detoxification, CGRP-pathway initiation, and acute regimen change?
Three concurrent strands. (1) Stop co-codamol abruptly with patient buy-in — frame as “the medication is making things worse, not better”. Counsel on 5–10 days of rebound headache. Bridging: prednisolone 60 mg tapering over 6 days, plus naproxen 500 mg twice daily for 14 days as needed (not exceeding 15 days/month). (2) Switch acute therapy from sumatriptan to rimegepant 75 mg ODT (NICE TA919) given her established ASCVD makes triptans contraindicated. Limit acute use to ≤ 8 days/month long-term. (3) Initiate a CGRP-pathway preventive — given that erenumab is the receptor-binding option and she has failed multiple traditional preventives plus botulinum, NICE TA682 / TA631 / TA659 / TA764 all permit initiation. Eptinezumab IV every 12 weeks has the strongest specific evidence in chronic migraine plus MOH (DELIVER 2024) and would be a defensible specialist choice; the alternative is fremanezumab quarterly SC.
Anchor. NICE TA682/631/659/764/919; DELIVER (Diener, Cephalalgia 2024); ICHD-3 §8.2 for MOH; AHS 2024 CGRP-first position.
Q2 · How do you address her PHQ-9 14 / GAD-7 12 alongside the headache plan?
Treat the depression and anxiety actively rather than attribute to headache alone. NICE NG222 / NG134 thresholds for pharmacological intervention are met. SSRI or SNRI alongside the headache plan is appropriate. Avoid combining triptans with high-dose SSRI / SNRI if any triptan use is retained — but the gepants she will now be on do not have this interaction. Refer to NHS Talking Therapies for high-intensity CBT; CBT for chronic migraine alongside CBT for depression has additive effect. Re-check PHQ-9 / GAD-7 at 8 weeks. Many patients with chronic headache see depression scores fall as headache burden falls; do not assume causation in either direction.
Anchor. NICE NG222 / NG134 / NG150; AHS 2024 on comorbid mood disorders in migraine.
Q3 · The chronic-migraine plan stabilises her for 6 months. She asks about “curing” her migraine — what is your answer?
Honest framing. Migraine is a chronic, episodic neurological condition with periods of remission. There is no cure, but the natural history is variable — many patients experience reduction in attack frequency from the late 50s onward. Chronic migraine often regresses to episodic migraine with sustained preventive therapy and MOH avoidance. After 12 months of clinically meaningful response on a CGRP-pathway preventive, NICE permits a planned trial off therapy to reassess underlying disease activity. About 30% of patients sustain benefit off therapy; the majority require continuation. The CAS framing is “reduction not cure, with a planned trial of stop at 12–24 months”.
Anchor. IHS Global Practice Recommendations 2024; NICE TA682/631/659/764/871/919 stop-rules; BASH chronic migraine pathway.
33-year-old woman on galcanezumab for chronic migraine, planning pregnancy
A 33-year-old solicitor with chronic migraine with aura (peak frequency 22 days/month previously) is now stable at 4 days/month after 9 months of galcanezumab 120 mg subcutaneous monthly (preceded by failed propranolol, candesartan, amitriptyline, topiramate). She is engaged and would like to conceive within 12 months. She had been on the COC for 12 years until aura onset 18 months ago — switched to LNG-IUS for contraception. Build her preconception, pregnancy, and postpartum plan.
Q1 · How long should galcanezumab be stopped before conception, and what replaces it?
Stop galcanezumab at least 5 months pre-conception. CGRP monoclonal antibodies have half-lives of approximately 27 (galcanezumab) – 30 (eptinezumab) days; five half-lives gives functional washout. The current European Headache Federation and IHS positions advise discontinuation pre-conception in the absence of robust human pregnancy data. Replace with a pregnancy-compatible preventive: propranolol 40 mg twice daily titrating to 80 mg twice daily is the best-evidenced option for preconception and pregnancy. She has failed propranolol previously — re-trial may still be appropriate as her current well-controlled state may now allow tolerability that the previous untreated severity did not. Amitriptyline 10–25 mg nocte is a reasonable alternative. Avoid topiramate (cleft lip/palate, hypospadias), sodium valproate (PPP — contraindicated in pregnancy), candesartan (foetal renal effects), CGRP-pathway agents.
Anchor. European Headache Federation pregnancy in headache 2022; IHS Global Practice Recommendations preventive 2024; MHRA antiepileptic-in-pregnancy bulletin; NICE NG150.
Q2 · What is her acute migraine plan during pregnancy?
Stratified by trimester and severity. First-line at all stages: paracetamol 1 g + antiemetic (cyclizine or prochlorperazine; metoclopramide also acceptable). Avoid NSAIDs in third trimester (premature ductus closure); first and second trimester acceptable below 20 weeks. Sumatriptan has the largest pregnancy dataset and is generally accepted second-line; prefer the SC route to limit total dose; the Swedish and Norwegian birth registries show no signal for major congenital malformations or stillbirth. Avoid ergotamines absolutely. Document the acute plan with pregnancy-specific dosing in advance.
Aura caveat. Migraine with aura confers a 1.5–2× background risk of pre-eclampsia, eclampsia, ischaemic stroke, and CVST. Aspirin 75–150 mg daily from 12 weeks is recommended in NICE NG133 for women with at least one moderate-risk factor for pre-eclampsia (migraine with aura is now considered such). Alongside obstetric risk factors, blood pressure surveillance is closer than for non-migraine pregnancies.
Anchor. NICE NG133 (hypertension in pregnancy); EHF 2022 pregnancy in headache; LactMed.
Q3 · She conceives, has a successful pregnancy, and is breastfeeding at 8 weeks postpartum. Migraine has returned to 12 days/month and propranolol is incompletely effective. What now?
The breastfeeding-compatible escalation pathway. Most acute migraine medications are LactMed-acceptable: paracetamol, ibuprofen, naproxen, sumatriptan SC. Preventive options compatible with breastfeeding: propranolol (her current), amitriptyline 10–25 mg nocte, riboflavin 400 mg/day, magnesium glycinate 400 mg/day. The CGRP-pathway agents — large molecules with limited oral bioavailability and minimal expected breast-milk transfer or infant absorption — are increasingly considered acceptable in breastfeeding although the safety database is small. Decision is shared with the patient, framed as low-but-not-zero theoretical risk vs maternal disability. If she chooses to restart galcanezumab during breastfeeding, document the conversation; alternatively delay restart until weaning. Aspirin 75–150 mg may be retained postpartum given persistent CV-risk implications of migraine with aura; document and individualise.
Anchor. LactMed (NIH); EHF 2022; NICE NG150 + NG133.
58-year-old man with chronic cluster headache refractory to verapamil
A 58-year-old electrician has had episodic cluster headache for 25 years, transitioned to chronic cluster 18 months ago (no remission > 3 months in past year). Currently 3–6 attacks per day, each 90 minutes severe periorbital pain with ipsilateral lacrimation and ptosis. He has home oxygen via HOOF Part B (effective ~ 60% of attacks); sumatriptan 6 mg subcutaneous twice daily as needed (limit 12/week). Verapamil titrated to 720 mg/day with PR-interval monitoring; ECG now shows PR 224 ms — verapamil at maximum tolerated dose with incomplete response. Co-existing hypertension (BP 142/86 on amlodipine 5 mg + ramipril 5 mg). BMI 31. He is a former smoker (quit 5 years). Build his refractory cluster plan.
Q1 · His cluster has transformed from episodic to chronic. What CGRP-pathway option is licensed in the UK, and where does it leave him?
NICE TA855 covers galcanezumab 300 mg monthly for episodic cluster only. Chronic cluster is currently outside NICE TA855 — an unmet need that the IHS, BASH and EHF have identified. Off-licence galcanezumab use in chronic cluster has been described in specialist series with reasonable response rates. The pragmatic UK pathway is: refer to a tertiary headache service for specialist sign-off and (in some ICBs) Individual Funding Request for galcanezumab in chronic cluster. Lithium is the alternative second-line preventive (started at 400 mg nocte titrated by lithium-level monitoring to a target trough of 0.6–0.8 mmol/L); evidence is older but reasonable. Topiramate 100–200 mg/day as adjunct.
Anchor. NICE TA855; IHS / BASH cluster pathway; EHF cluster guidance.
Q2 · His verapamil PR interval is 224 ms. How do you proceed?
PR > 220 ms is the BASH stop threshold for verapamil. Reduce dose by 80 mg (one tablet); recheck ECG in 1–2 weeks. If PR normalises, retain at the lower dose; if still > 220 ms, taper off completely. The verapamil ECG-monitoring schedule is: ECG before each 80 mg dose increase; after stable dose for 1 month then every 6 months thereafter. Bradycardia < 50 bpm or new bundle branch block also stops escalation. Cardiology liaison is appropriate when high-dose verapamil is required.
Anchor. BASH cluster guidance 2019/2024; verapamil cardiac monitoring protocol.
Q3 · His sumatriptan use is 12 doses per week (24 per fortnight). Could he have MOH? And what neuromodulation options exist?
MOH in cluster is a separate ICHD-3 entity (§8.2.4) but the threshold differs. Cluster patients use high triptan doses by necessity; the ICHD-3 distinction is whether his interictal headache pattern has changed or worsened, suggesting overlay. Document any change in baseline tone or background headache pattern; if present, consider tapering sumatriptan via increased reliance on O₂ and adding lithium / topiramate.
Neuromodulation options. (a) Non-invasive vagus nerve stimulation (gammaCore) — UK-available; FDA-cleared for cluster; reasonable adjunct for both acute and preventive. (b) Sphenopalatine ganglion stimulation (Pulsante / Autonomic Technologies) — implanted neurostimulator; specialist; promising in chronic cluster. (c) Occipital nerve stimulation — implanted; longer-established; specialist neurosurgical centres only. (d) Deep brain stimulation of posterior hypothalamus — last-resort for refractory chronic cluster; very specialist. Refer to a tertiary headache service to coordinate neuromodulation pathway.
Anchor. ICHD-3 §8.2.4; gammaCore NHS evaluation; BASH cluster pathway; IHS guidance.
Twelve items across the four CAS pillars — alongside the three embedded in-section knowledge checks
Twelve items in clinical-vignette format pitched at synoptic-CAS level (above MRCGP-AKT). Each item has a single best answer and four defensible-but-wrong distractors with explicit guideline citation in the rationale. The twelve items below are in addition to the three embedded mini-SBAs at the end of the acute migraine (Section 05), preventive ladder (Section 06), and CGRP-pathway (Section 07) sections — fifteen items in total across the module.
How to use this integrative check. Work through all twelve items in one sitting before opening the rationales — this trains the synoptic-style synthesis the CAS assessments require. Aim for ≥ 9 / 12 across the integrative check, plus ≥ 2 / 3 across the embedded mini-SBAs. The two paired sample synoptic self-assessments — Migraine and Cluster Headache & TACs — are the 20-item instruments designed for revision and self-assessment after the module.
MRCGP-AKT format with a single best answer and four defensible-but-wrong distractors. Several items sit at CAS challenge level requiring synthesis across guideline frameworks. Each rationale cites the specific NICE / BASH / IHS source.
SBA 1 · Diagnosis · 38-year-old woman with episodic moderate headache
A 38-year-old woman presents with 6 episodes per month, each 18–24 hours, of unilateral pulsating moderate-to-severe headache with photo- and phonophobia, nausea, and aggravation by movement. She rests in a darkened room until resolution. No focal neurology. Family history of migraine (mother). BP 118/76; neuro exam normal. What is the most likely diagnosis?
Correct answer: A. She meets all ICHD-3 §1.1 criteria — at least 5 attacks (she has many more), 4–72 hours, ≥ 2 of (unilateral, pulsating, moderate-severe, aggravated by movement — she has all four), ≥ 1 of (nausea/vomiting, photo-/phonophobia — she has both). TTH (B) lacks the unilateral, pulsating, severe, movement-aggravated features. Cluster (C) is brief (15–180 min), severe orbital, autonomic features. Hemicrania continua (D) is continuous. MOH (E) requires medication-overuse pattern.
SBA 2 · Red flags · 56-year-old with new headache and scalp tenderness
A 56-year-old woman attends with 3 weeks of new daily headache, worsening, with scalp tenderness particularly when brushing hair, jaw discomfort on chewing, and one episode of transient blurred vision in the right eye lasting 5 minutes. ESR 88 mm/h, CRP 65 mg/L. What is the immediate priority?
Correct answer: C. Classic giant cell arteritis pattern — age ≥ 50, new headache, scalp tenderness, jaw claudication, transient visual disturbance, raised inflammatory markers. Steroid must be started immediately (prednisolone 60 mg/day) before biopsy; visual loss is often irreversible if treatment is delayed. NICE NG150 + BSR concur. Routine ophthalmology (A), migraine therapy (B), delayed imaging (D), or watchful waiting (E) all carry irreversible visual-loss risk.
SBA 3 · Acute · 28-year-old triptan-naive woman with severe migraine attacks
A 28-year-old woman has 4 severe migraine attacks per month, each lasting 12–18 hours, partially responsive to ibuprofen 600 mg + paracetamol 1 g + metoclopramide 10 mg. Attacks involve severe vomiting from outset. No CVD, no aura, BMI 24, BP 116/74. What is the most appropriate triptan choice and route?
Correct answer: B. Severe vomiting from attack onset means oral absorption is unreliable. Subcutaneous sumatriptan or intranasal zolmitriptan bypass the gastric route, give faster onset, and are NICE NG150 / BASH first-line in vomiting migraine. Frovatriptan (A) and naratriptan (C) are slow-onset and intended for predictable mini-prophylaxis (e.g. menstrual migraine). Codeine (D) carries MOH risk and minimal evidence. Pethidine (E) is contraindicated.
SBA 4 · Preventive · 41-year-old woman with episodic migraine and hypertension
A 41-year-old woman has 7 migraine days per month and untreated hypertension (BP 152/92 over three readings, eGFR 78). No CVD, BMI 26, no asthma, no diabetes. She has not previously trialed any preventive. What is the most appropriate first-line preventive?
Correct answer: D. Candesartan provides dual benefit — migraine prevention (off-licence but well-evidenced; BASH-supported) and hypertension treatment (on-licence). Two indications, one tablet, no extra side effects. Atogepant (A) and erenumab (E) are NICE-positive only after three traditional preventive failures. Topiramate (B) has the “cognitive fog” profile and contraceptive interactions to consider in this premenopausal patient. Sodium valproate (C) is contraindicated in women of childbearing potential without PPP enrolment.
SBA 5 · CGRP-pathway · selecting between mAbs in chronic migraine
A 47-year-old woman has chronic migraine refractory to propranolol, topiramate, amitriptyline, and onabotulinumtoxinA (two PREEMPT cycles, 25% response). She works as a paediatric anaesthetist with an irregular shift pattern; needle-fearful but copes; values long dosing intervals where possible. eGFR 80, no constipation history. Which CGRP-pathway agent is best matched to her preferences?
Correct answer: B. Fremanezumab is uniquely available as a quarterly 675 mg dose (three pre-filled syringes given consecutively at each visit), making it the longest-interval CGRP option — best matched for a needle-fearful patient with irregular shift work. Erenumab (A) and galcanezumab (C) are monthly. Atogepant (D) and rimegepant (E) are daily oral — adherence challenge with shift work. NICE TA631 (fremanezumab) covers her indication.
SBA 6 · Cluster · acute management
A 39-year-old man with newly diagnosed episodic cluster headache (typical pattern; bout-onset; 4 attacks per day; severe ipsilateral periorbital pain; lacrimation and ptosis). MRI brain normal. He attends with a fresh attack 30 minutes ago, still in pain. What is the most appropriate acute treatment?
Correct answer: A. 100% oxygen at 12–15 L/min via non-rebreather mask for 15–20 minutes is first-line acute therapy in cluster headache (NICE NG150, BASH 2019/2024). Aborts ~ 70% of attacks within 15 minutes. Subcutaneous sumatriptan 6 mg is the second-line acute. Oral sumatriptan (C) is too slow given typical 15–180 minute attacks. Simple analgesics (B), indomethacin (D — useful in paroxysmal hemicrania, not cluster), and codeine (E) are inappropriate.
SBA 7 · TAC differentiation · indomethacin trial
A 44-year-old woman has 6 months of severe unilateral right-sided pain, 12–25 minutes per attack, 8–10 attacks per day, with ipsilateral lacrimation and rhinorrhoea. She has been treated as “atypical cluster” with verapamil and zolmitriptan with limited success. MRI brain unremarkable. What is the most diagnostically useful next step?
Correct answer: E. Her attack duration (2–30 min) and frequency (5–40/day) plus autonomic features fit ICHD-3 §3.2 paroxysmal hemicrania, not cluster. Indomethacin response is diagnostic: complete or near-complete pain abolition within 1–2 weeks of titration. The agents listed (A, B, C, D) all target cluster physiology and have limited effect in paroxysmal hemicrania. Misdiagnosis of paroxysmal hemicrania as cluster is one of the highest-yield correctable diagnostic errors in headache medicine.
SBA 8 · MOH · diagnosis and detoxification
A 51-year-old woman has 22 headache days per month for the past 9 months. Started as 6 migraine days per month 5 years ago. Now uses sumatriptan 50 mg on 14 days per month plus paracetamol 1 g + ibuprofen 400 mg almost daily. Failed amitriptyline (sedation) and propranolol (bradycardia). Headache pattern has become “dull background with overlying spikes”. What is the most appropriate next step?
Correct answer: D. She meets ICHD-3 §8.2 MOH criteria — triptan use ≥ 10 days/month for ≥ 3 months PLUS simple analgesic use ≥ 15 days/month (combination of overuse). Detoxification is essential. Abrupt withdrawal with prednisolone 60 mg tapering over 6 days bridge is BASH-endorsed. Concurrent preventive initiation (CGRP pathway, given the failed traditional preventives, is NICE-permitted) is the contemporary approach per DELIVER 2024. Adding more acute medication (A — wrong sequence; E — opioid contraindicated) or continuing without diagnosis (B, C) misses the iatrogenic transformation.
SBA 9 · Pregnancy · acute migraine
A 31-year-old woman, 18 weeks pregnant with her second child, presents with a severe migraine without aura — typical of her pre-pregnancy pattern. Paracetamol 1 g + cyclizine 50 mg has not aborted the attack at 4 hours. What is the most appropriate next step?
Correct answer: A. Sumatriptan has the largest pregnancy dataset of any acute migraine therapy and is generally accepted as second-line in pregnancy after paracetamol — Swedish and Norwegian birth registries show no signal for malformation or stillbirth. Subcutaneous route limits total dose. NSAIDs (B) acceptable in second trimester but generally avoided beyond 28–30 weeks (premature ductus closure). Codeine (C) carries opioid concerns. Topiramate (D) is teratogenic. CGRP mAbs (E) are not for acute treatment and have limited pregnancy data.
SBA 10 · Perimenopause · migraine + aura on COC
A 47-year-old woman with longstanding migraine with aura attends with worsening symptoms. She has been on Microgynon 30 (combined oral contraceptive) for 12 years. Aura frequency has increased from 1–2 episodes per year to 3 in the last month. BMI 24, BP 122/76. Last menstrual period 5 weeks ago. What is the most appropriate management?
Correct answer: C. New or worsening aura on combined hormonal contraception is FSRH UKMEC 4 — stop COC immediately given arterial-thrombotic risk. Switch to a progestogen-only method (POP desogestrel, LNG-IUS, Nexplanon) for contraception. The BMS 2022 / FSRH joint position permits transdermal HRT in migraine with aura where VMS warrant treatment — but oral oestrogen-containing HRT (B, D) carries the same arterial-risk concern as the COC.
SBA 11 · Pipeline · interpretation of PFO closure evidence
A 32-year-old woman with refractory migraine with aura has had a bubble study showing a moderate-grade right-to-left shunt; cardiology have confirmed a 6 mm patent foramen ovale on TOE. She has read about PFO closure on social media and asks whether she should pursue it. She has failed amitriptyline, propranolol, topiramate, and is currently on month 4 of fremanezumab with 30% improvement. What is the most evidence-based response?
Correct answer: B. Three randomised trials of PFO closure for migraine — MIST, PRIMA, PREMIUM — failed to meet their primary endpoints. Subgroup analyses suggested possible benefit in migraine-with-aura patients but these are hypothesis-generating only. The IHS, ACC, and NICE have not endorsed PFO closure for migraine alone. Recommending closure as standard (A, C) misrepresents the evidence. Declining all intervention (D) ignores her ongoing burden — continue optimising preventive therapy. Aspirin (E) is reasonable secondary CV prevention given migraine with aura but does not directly substitute for the PFO question.
SBA 12 · Trigeminal neuralgia in headache differential
A 64-year-old man has 4 weeks of brief paroxysms of severe right-sided cheek pain, like “electric shocks”, lasting 1–10 seconds, triggered by chewing, brushing teeth, and a cold breeze. Many paroxysms per day. No autonomic features. Neuro exam normal. MRI shows a vascular loop of the superior cerebellar artery contacting the trigeminal nerve root. What is the most appropriate first-line treatment?
Correct answer: E. ICHD-3 §13.1.1.1 — classical trigeminal neuralgia. Carbamazepine is first-line per NICE NG150; titrate slowly to avoid sedation, dizziness; check FBC, U&Es, LFTs at baseline and periodically (rare aplastic anaemia, hyponatraemia). Oxcarbazepine is the second-line equivalent; gabapentin and lamotrigine are alternatives. Microvascular decompression (D) is the gold-standard surgical option after medical failure — not first-line. Triptans (A), indomethacin (B), and botulinum (C) are not standard for TN.
Self-marking. Twelve items at AKT-to-CAS challenge level. Distribution of correct answers across A–E aims for balance. Ten or more correct = strong CAS competence; 8–9 = solid AKT level; ≤ 7 = revisit the corresponding section before progressing to the full units. The full Headache & Migraine CAS — a standalone FHEQ Level 7 award of 20 UK credits / 10 ECTS — is assessed by a confidence-calibrated applied-knowledge paper, a workplace capstone and a short defended presentation.
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Answer the items, mark your work, add a reflection, and download a personalised CPD certificate.
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Four-quadrant blueprint
Migraine without / with aura · chronic migraine · hemiplegic · vestibular · ICHD-3 thresholds.
NICE NG150 stratified care · UK triptan portfolio · gepants · ditans · triptan contraindications.
Beta-blockers · candesartan · topiramate · amitriptyline · sodium valproate (PPP) · botulinum TA260.
CGRP mAbs · gepants · switching mechanisms · MOH · pregnancy · perimenopausal aura · PFO.
How it works. Select your answer for each item. Your selection is recorded but not marked. When all twenty are answered, click Mark my answers at the foot of the quiz. The results panel reveals the correct answer for each item plus a 60–120-word rationale focused on why the correct answer is correct, with one hyperlinked guideline reference per item. The certificate at the foot auto-populates with your name, date, score, quadrant breakdown, and personal reflection.
Q1 · ICHD-3 migraine without aura Diagnosis
A 38-year-old woman has 6 episodes/month, each 18–24 hours, of unilateral pulsating moderate-severe headache with photo- and phonophobia, nausea, and aggravation by movement. Family history of migraine. Most likely diagnosis?
Q2 · ICHD-3 chronic migraine Diagnosis
A 45-year-old has headache for ≥ 15 days/month for the past 6 months, of which 9 days/month meet migraine criteria. Diagnosis?
Q3 · Aura definition Diagnosis
A 31-year-old has reproducible 20–30-minute episodes of zigzag scintillating visual disturbance starting centrally and spreading to a hemifield, followed within 1 hour by a unilateral pulsating headache. Diagnosis?
Q4 · ★ Professor-level Hemiplegic migraine acute therapy Diagnosis
A 28-year-old man has 3 episodes over 2 years of unilateral motor weakness lasting 30–60 minutes followed by classical migraine. Father had similar attacks. Genetic testing reveals a CACNA1A mutation. He attends with a fresh attack — weakness on the left and severe right-sided headache. BP 134/80. ECG sinus rhythm. Most appropriate acute therapy?
Q5 · Vestibular migraine Diagnosis
A 42-year-old woman has 6 episodes over 12 months of vertigo lasting hours, with photophobia and movement-aggravated head discomfort. No tinnitus or hearing loss. Migraine without aura previously diagnosed. Most likely diagnosis?
Q6 · Severe vomiting at onset — route of triptan Acute
A 28-year-old triptan-naive woman has 4 severe migraine attacks/month, each 12–18 h, with severe vomiting from onset. No CVD, no aura, BMI 24, BP 116/74. Most appropriate triptan choice and route?
Q7 · Triptan contraindication after MI Acute
A 36-year-old woman with migraine without aura had an unprovoked NSTEMI 4 months ago (presumed coronary spasm). On aspirin, ticagrelor, atorvastatin, ramipril, bisoprolol. Migraine attacks 2–3/month, 24–36 h, severe with vomiting. NSAIDs partially effective. BP 122/76. ECG normal. Most appropriate acute therapy?
Q8 · Triptan switching Acute
A 32-year-old woman has used sumatriptan 100 mg orally for 2 years for migraine without aura — initially effective, now “not working”. NSAIDs + paracetamol pre-dose tried. BP normal, no CVD. Most appropriate next step?
Q9 · Gepant choice — preference for oral once-daily Acute
A 44-year-old woman with infrequent severe migraine attacks (about 2/month). Triptans previously — modest efficacy with chest tightness side effect. No CVD on workup. She prefers oral therapy and finds tablets easier than nasal sprays. Most appropriate gepant?
Q10 · ★ Professor-level MOH detoxification Acute
A 51-year-old woman has 22 headache days/month for 9 months. Started as 6 days/month 5 y ago. Sumatriptan 50 mg on 14 d/m + paracetamol/ibuprofen almost daily. Failed amitriptyline (sedation), propranolol (bradycardia). Headache pattern “dull background with overlying spikes”. Most appropriate next step?
Q11 · First-line preventive in childbearing-potential woman Preventive
A 28-year-old woman has 7 migraine days/month, no contraception, long-term partner, undecided about pregnancy. BMI 22, BP 116/74. Most appropriate first-line preventive per NICE NG150?
Q12 · Candesartan as preventive Preventive
A 41-year-old woman has 7 migraine days/month and untreated hypertension (BP 152/92, eGFR 78). No CVD, BMI 26, no asthma, no diabetes. No previous preventive trialed. Most appropriate first-line preventive?
Q13 · Topiramate counselling Preventive
A 35-year-old woman with episodic migraine is starting topiramate 25 mg titrating to 50 mg twice daily. She uses Microgynon 30 (COC) for contraception. Which counselling point is essential?
Q14 · Botulinum toxin NICE TA260 Preventive
A 38-year-old woman has chronic migraine (18 headache days/month, 11 of which migrainous, for 6 months). Failed propranolol, topiramate, amitriptyline at adequate doses. Currently sumatriptan 8 days/month. Per NICE TA260, which therapy is licensed?
Q15 · ★ Professor-level Refractory chronic migraine — CGRP selection by lifestyle fit Preventive
A 47-year-old woman with chronic migraine refractory to propranolol, topiramate, amitriptyline, and onabotulinumtoxin A (two PREEMPT cycles, 25% response). Works as paediatric anaesthetist with irregular shift pattern; needle-fearful but copes; values long dosing intervals. eGFR 80, no constipation history. Which CGRP-pathway agent is best matched to her preferences?
Q16 · CGRP mAb mechanism switching CGRP & special pops
A 42-year-old woman with chronic migraine refractory to multiple preventives + onabotulinumtoxin A is on month 4 of erenumab 140 mg monthly with only 15% reduction in monthly headache days — does not meet the NICE 30% chronic-migraine continuation rule. Most appropriate next step?
Q17 · Acute migraine in pregnancy CGRP & special pops
A 31-year-old woman, 18 weeks pregnant with second child, presents with severe migraine without aura — typical of her pre-pregnancy pattern. Paracetamol 1 g + cyclizine 50 mg has not aborted at 4 hours. Most appropriate next step?
Q18 · Perimenopausal migraine + aura on COC CGRP & special pops
A 47-year-old woman with longstanding migraine with aura attends with worsening symptoms. On Microgynon 30 for 12 years. Aura frequency increased from 1–2/y to 3 in last month. BMI 24, BP 122/76. Last period 5 weeks ago. Most appropriate management?
Q19 · CGRP mAb pregnancy washout CGRP & special pops
A 33-year-old woman on galcanezumab 120 mg SC monthly for chronic migraine (well-controlled at 4 days/month) is engaged and would like to conceive within 12 months. How should galcanezumab be managed pre-conception?
Q20 · ★ Professor-level PFO closure for migraine with aura CGRP & special pops
A 32-year-old woman with refractory migraine with aura has had a bubble study showing moderate-grade right-to-left shunt; cardiology have confirmed a 6 mm patent foramen ovale on TOE. She has failed amitriptyline, propranolol, topiramate, and is on month 4 of fremanezumab with 30% improvement. She has read about PFO closure online and asks whether she should pursue it. Most evidence-based response?
Personal reflection — for your CPD portfolio
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MD Acumen School of Postgraduate Medicine
This certifies that
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Migraine Synoptic Self-Assessment — 20 single-best-answer items at CAS tier
Authored by Prof Rajesh Varma · MD Acumen Ltd · mdacumen.com
Curriculum-aligned with NICE NG150 / CG150; ICHD-3; 2025 IHS-Italian Society pharmacological guidelines (Ornello, Cephalalgia 2025); IHS Global Practice Recommendations (Puledda 2024); contemporary CGRP-era NICE TA portfolio.
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Key sources & further reading
All clinical content drawn from independent peer-reviewed and recognised guideline-issuing bodies. Where multiple licensed agents within a class are discussed, they are presented even-handedly per their NICE technology appraisals.
Expanded source list
NICE NG150. Headaches in over-12s: diagnosis and management. · ICHD-3 (Headache Classification Committee of the International Headache Society) 2018. · Ornello R et al. Evidence-based guidelines for the pharmacological treatment of migraine — summary version. Cephalalgia 2025;45. · Puledda F, Sacco S, Diener H-C et al. International Headache Society global practice recommendations for the acute pharmacological treatment of migraine. Cephalalgia 2024;44. · Puledda F et al. International Headache Society global practice recommendations for preventive pharmacological treatment of migraine. Cephalalgia 2024;44. · Do TP et al. Red and orange flags for secondary headaches in clinical practice: SNNOOP10 list. Neurology 2019;92:134–144. · Diener HC et al. Eptinezumab in chronic migraine and medication-overuse headache (DELIVER). Cephalalgia 2024. · Lederman S et al. Lasmiditan: novel 5-HT1F receptor agonist. Lancet Neurology 2019. · NICE TAs 260, 631, 659, 682, 764, 855, 871, 919, 973, 1132 (current at module date). · Goadsby PJ. Calcitonin gene-related peptide-targeted therapy in migraine: current role and future perspectives. Lancet 2025. · Hodis HN et al. The window of opportunity for coronary heart disease prevention with hormone therapy. Climacteric 2013 (referenced for cross-pillar timing-hypothesis context). · BASH cluster headache pathway 2019/2024. · MacGregor EA et al. Migraine and the menopause: a joint BMS/FSRH/BASH position statement. BMS 2022. · NICE TA906 · zavegepant intranasal · pending TA. · European Headache Federation 2022 — pregnancy in headache. · Pinkerton JV et al. Elinzanetant phase-3 (OASIS) — JAMA 2024 (cross-reference to menopause module). · BHV-2100 phase 2 — AAN 2025 abstract. · TEMPLE trial — atogepant vs topiramate · readout May 2026. · ShiraTronics RELIEV-CM pilot data 2025. · MIST, PRIMA, PREMIUM trials — PFO closure for migraine.
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