Migraine prophylaxis
Preventive therapy for episodic or chronic migraine when attacks occur 4 or more times per month or significantly impair quality of life. AAN 2019 classifies propranolol at level A.
ICD-10 G43.911 drugs
Also known as: Migraine prevention
Drugs used for this condition
- AFlunarizineSecond line · Selective calcium channel blocker, antivertigo and migraine prophylaxis agentSecond-line for migraine prophylaxis per AAN/AHS 2024 and EFNS 2022 after β-blockers (propranolol, metoprolol), topiramate, and CGRP antagonists. The 2017 Cochrane meta-analysis showed a 35–50% reduction in migraine attack frequency. Standard dose 5–10 mg once daily at bedtime. Six-month course with a 6-month break to reassess the need to continue.
- APropranololFirst line · Non-selective beta blockerPropranolol reduces migraine attack frequency by at least 50 percent in half of patients at 80–240 mg/day. AAN 2019 classifies it at level A: first-line prevention alongside topiramate, metoprolol, and timolol. Effect develops over 4–8 weeks. Preferred in patients with co-existing hypertension or anxiety; avoided in asthma, symptomatic bradycardia, and depression.
- ATopiramateFirst line · Antiepileptic with multiple mechanismsFirst-line in migraine prophylaxis per AAN/AHS 2012 and EFNS 2009 alongside β-blockers (propranolol, metoprolol). Reduces attack frequency by 50% in 35–50% of patients. Dose 50–100 mg daily in 2 doses. In obese patients, an added benefit – weight loss of 3–5 kg.
- BAmitriptylineSecond line · Tricyclic antidepressants (TCA)Amitriptyline is licensed in Spain for migraine prophylaxis in adults (Tryptizol SmPC, section 4.1). The systematic review behind the AAN/AHS 2026 guideline rates its evidence in episodic migraine as low confidence, while propranolol, topiramate and valproate have moderate confidence; in the AAN/AHS 2012 version it was Level B. The European EHF 2021 recommendations place it in the second line after beta-blockers, topiramate and candesartan, and call it the most likely to help when depression or sleep disturbance coexist. Guidelines diverge: NICE CG150 (updated 2025) lists it alongside propranolol and topiramate, and the SEN 2020 headache manual gives it evidence level I, grade A, preferring it when migraine coexists with tension-type headache or depression. For that reason the card lists it as second line, with first choice reserved for those comorbidities. In a 26-week RCT (Dodick, 2009; n=331), amitriptyline and topiramate up to 100 mg/day reduced attacks by the same amount (−2.7 and −2.6 per month), but weight rose by 2.4 kg on average with amitriptyline. Start with 10–25 mg at bedtime, usual dose 25–75 mg; over age 65 and in heart disease doses above 75 mg need caution, and the AGS Beers Criteria 2023 advise older adults to avoid it. Contraindicated after a recent myocardial infarction, with heart block or arrhythmia, coronary insufficiency, severe liver disease and with MAOIs. It prolongs QT and can trigger angle-closure glaucoma and urinary retention; in people under 25, suicidal thoughts may increase early in treatment. Fluoxetine, paroxetine and bupropion raise its levels; with tramadol the risk of seizures and serotonin syndrome increases. In pregnancy it is used only when clearly needed; 0.6–1% of the maternal dose passes into breast milk. Overdose is cardiotoxic and can be fatal, which matters for patients at risk of suicide.
- BCandesartanSecond line · Angiotensin II receptor blockerCandesartan reduces migraine attack frequency by 26 percent versus placebo in the Tronvik RCT (JAMA 2003) at 16 mg daily for 12 weeks. AAN 2019 classifies candesartan at evidence level C: considered as second-line in patients with contraindications to topiramate, propranolol, and amitriptyline, or with co-existing hypertension. Off-label in the Russian Federation.
- BMagnesium (oral salts: citrate, glycinate, oxide, sulfate)Add-on therapy · Mineral supplements. MacromineralsMagnesium citrate or oxide 400–600 mg daily is considered for migraine prophylaxis in patients with contraindications to beta-blockers and topiramate and in women planning pregnancy. Cochrane 2022 rated the effect as modest but clinically meaningful: 20–40% reduction in attack frequency versus placebo. AAN 2012 classifies magnesium as level B (probably effective). The effect develops after 4–8 weeks.
- BRiboflavinAdd-on therapy · Water-soluble vitamin B2Riboflavin 400 mg/day received Level B (probably effective) in the 2012 AAN/AHS guideline for episodic migraine prevention. Meta-analyses show 1.5–2.5 fewer attacks per month after 3 months of treatment. SEN 2020 lists riboflavin as an option when beta-blockers, topiramate and CGRP antagonists are contraindicated – particularly for patients preferring «natural» therapy and adolescents where topiramate is restricted. Cochrane 2015 acknowledges the positive signal with a favourable safety profile but calls for larger trials. Paediatric data are limited; dose is weight-adjusted. Effect develops slowly – assess at 3 months of uninterrupted use.
- BUbidecarenone (coenzyme Q10)Add-on therapy · Other cardiac preparations. Coenzyme Q10Coenzyme Q10 is considered as preventive therapy in episodic migraine, particularly in patients intolerant to topiramate, β-blockers, or amitriptyline. RCTs Sandor 2005 (n=42), Shoeibi 2017 (n=80), and the Zeng 2018 meta-analysis (5 RCTs) show 30–50% reduction in attack frequency at 300 mg/day (100 mg three times). Effect develops over 3 months. AAN/AHS 2012 and European Headache Federation guidelines classify CoQ10 as category C («possibly effective») – an acceptable option when first-line prophylaxis is contraindicated. EHF guidelines also list CoQ10 as an option in children.
- BValproic acidSecond line · Antiepileptics. Fatty acid derivativesValproate is included in international guidelines (AAN/AHS, EHF) as a drug with proven efficacy in episodic migraine prophylaxis. Reduces attack frequency by 50% in some patients. Used when first-line agents (beta-blockers, topiramate, anti-CGRP monoclonal antibodies) are ineffective or intolerable. Not used in women of reproductive age due to teratogenicity.
- BVerapamilSecond line · Non-dihydropyridine calcium channel blockerVerapamil is considered second-line for migraine prevention, particularly with co-existing hypertension. AAN 2019 classifies it as level U (insufficient evidence) for classic migraine and level C for cluster headache at 240–480 mg daily. Off-label in the Russian Federation, with individual dosing under PR-interval monitoring on ECG.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit