Pharmacological management of migraine: current strategies and future directions

Figures & data

Table 1. Acute migraine therapies. Therapeutic gain (TG), i.e. The difference between the active drug and placebo, for pain freedom at 2 hours is reported.

Therapy	TG	Reference
Simple analgesics
Paracetamol 1,000 mg	8%	[73]
Aspirin 1,000 mg	13%	[7]
Diclofenac potassium 50 mg	14%	[10]
Ibuprofen 400 mg	14%	[8]
Naproxen 500 mg or 825 mg	9%	[9]
Oral triptans
Almotriptan 12.5 mg	22%	[16]
Eletriptan 40 mg	27%	[16]
Frovatriptan 2.5 mg	11%	[16]
Naratriptan 2.5 mg	13%	[16]
Rizatriptan 10 mg	35%	[16]
Sumatriptan 50 mg	16%	[16]
Sumatriptan 100 mg	21%	[16]
Zolmitriptan 2.5 mg	20%	[16]
Zolmitriptan 5 mg	21%	[16]
Combination
Oral sumatriptan 85 mg + naproxen 500 mg	20%	[16]
Nasal triptans
Sumatriptan 20 mg	21%	[16]
Zolmitriptan 5 mg	25%	[16]
Subcutaneous triptans
Sumatriptan 6 mg	44% (34% for 1 h pain free)	[16]
Ditans
Lasmiditan 50 mg	7%	[16]
Lasmiditan 100 mg	12%	[16]
Lasmiditan 200 mg	17%	[16]
Gepants
Rimegepant 75 mg tablet	8%	[16]
Rimegepant 75 mg orally disintegrating tablet	11%	[16]
Ubrogepant 25 mg	6%	[16]
Ubrogepant 50 mg	8%	[16]
Ubrogepant 100 mg	9%	[16]
Zavegepant 10 mg	8%	[74]

Table 2. Preventive migraine therapies. Adapted from Eigenbrodt AK et al. [6].

Drug class	Drug	Dosage and route	Contraindications
First-line medication
Beta blockers	Atenolol*	25–100 mg oral twice daily	Asthma, cardiac failure, atrioventricular block
	Bisoprolol*	5–10 mg oral once daily
	Metoprolol	50–100 mg oral twice daily or 200 mg modified-release oral once daily
	Propranolol	80–160 mg oral once or twice daily in long-acting formulations
Angiotension II-receptor blocker	Candesartan*	16–32 mg oral per day	Co-administration of aliskiren
Anti-seizure medication	Topiramate	50–100 mg oral daily	Neprolithiasis, pregnancy, lactation, depression, glaucoma
Second-line medication
Tricyclic antidepressant	Amitriptyline	10–100 mg oral at night	Co-administration of monoamine oxidase inhibitors, heart failure, glaucoma, atrioventricular block
Calcium antagonist	Flunarizine	5–10 mg oral once daily	Parkinsonism, depression
Anti-seizure medication	Sodium valproate	600–1,500 mg oral once daily	Liver disease, thrombocytopenia, women of childbearing potential
Third-line medication
Botulinum toxin	Onabotulinumtoxin A	155–195 units at 31–39 injection sites every 3 months	Infection at injection site
Calcitonin gene-related peptide monoclonal antibodies	Erenumab	70 or 140 mg subcutaneous once monthly	Not recommended in patients with a history of stroke, subarachnoid hemorrhage, coronary heart disease, inflammatory bowel disease, chronic obstructive pulmonary disease or impaired wound healing.
	Fremanezumab	225 mg subcutaneous once monthly or 675 mg subcutaneous once quarterly
	Galcanezumab	240 mg subcutaneous, then 120 mg subcutaneous once monthly
	Eptinezumab	100 or 300 mg intravenous quarterly
Small molecule calcitonin gene-related peptide receptor antagonists (gepants)	Atogepant Rimegepant	10 mg, 30 mg, or 60 mg once daily 75 mg every other day	Liver disease, concomitant use with strong CYP3A4 inhibitors

*Efficacy tested in less than three clinical trials.

Table 3. Several pharmacological therapies that are in development for migraine.

Drug(s)	Mode of action	Indication	Status
Lu AG09222 and LY3451838	PACAP-targeted mAbs	Migraine prevention	Phase 2
AGX-201	Histamine receptor modulator	Migraine prevention	Phase 2
Vaporized CBD and THC	Modulator of the endocannabinoid system	Acute migraine treatment	Phase 2
Oral CBG, CBD and THC	Modulator of the endocannabinoid system	Migraine prevention	Phase 4
Oral CBD	Modulator of the endocannabinoid system	Migraine prevention	Phase 2
Intranasal oxytocin	Oxytocin receptor agonist	Migraine prevention	Phase 2
Sepranolone	Allosteric modulator of the GABAA receptor	Menstrual migraine prevention	Phase 2
Tricaprilin	Inducer of ketosis	Migraine prevention	Phase 2
Meloxicam and rizatriptan	COX2 inhibitor and 5-HT1B/1D receptor agonist	Acute migraine treatment	Pre-registration
Prabotulinumtoxin A	Botulinum toxin	Migraine prevention	Phase 2
Abobotulinumtoxin A	Botulinum toxin	Migraine prevention	Phase 3
Incobotulinumtoxin A	Botulinum toxin	Migraine prevention	Phase 3

5-HT: serotonin; CBD: cannabidiol; CBG: cannabigerol; COX: cyclooxygenase; GABA: γ-aminobutyric acid; mAb: monoclonal antibody; THC: delta-9-tetrahydrocannabinol.

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