What is the role of flunarizine in adult migraine prophylaxis, including recommended dosing, efficacy, common adverse effects, contraindications, and its availability in the United States?

Flunarizine in Adult Migraine Prophylaxis

Flunarizine 5–10 mg once daily at bedtime is an effective second-line agent for migraine prophylaxis in adults, with efficacy comparable to propranolol and topiramate, but it is not available in the United States. 1

Clinical Positioning in Treatment Algorithm

• First-line agents should be tried before flunarizine, including propranolol (80–240 mg/day), timolol (20–30 mg/day), topiramate (50–100 mg/day), or candesartan. 1
• Flunarizine is recommended as a second-line option after failure or intolerance of first-line beta-blockers or topiramate. 1
• The European Neurological Society supports flunarizine as an effective second-line preventive agent where available. 1

Recommended Dosing

• The standard dose is 10 mg once daily, taken at night to minimize daytime sedation—this is the most commonly studied and used dose. 1, 2, 3
• An alternative dose of 5 mg once daily can be used for patients concerned about side effects, particularly weight gain or sedation. 1
• Doses up to 15 mg daily have been used and are generally well tolerated. 3

Evidence for Efficacy

• Flunarizine reduces migraine attack frequency by 0.4 attacks per 4 weeks compared to placebo (pooled analysis of 5 trials, 249 participants). 2
• Flunarizine is comparable in effectiveness to propranolol (pooled analysis of 7 trials, 1,151 participants showed no significant difference). 1, 2
• In a UK tertiary headache practice cohort of 200 patients, 76% reported clinical benefit, with 64% continuing treatment for more than 1 year. 3
• Flunarizine reduces both the severity and duration of individual migraine attacks, though its effect on attack frequency may be more modest. 4

Implementation Strategy

• Start with 5–10 mg once daily at bedtime and allow an adequate trial period of 2–3 months before assessing efficacy. 1
• Track attack frequency, severity, and disability using headache diaries to objectively measure response. 1
• Schedule follow-up visits within 2–3 months to assess for side effects and efficacy. 1

Common Adverse Effects

• Sedation and daytime tiredness are the most frequently reported side effects. 1, 3, 4
• Weight gain occurs commonly and should be discussed with patients before initiation. 1, 3, 4, 5
• Abdominal pain may occur. 1
• In the UK cohort, only 10.5% of patients discontinued treatment due to adverse effects, indicating generally good tolerability. 3

Serious Adverse Effects and Contraindications

Absolute Contraindications

• Active Parkinsonism or history of extrapyramidal disorders (flunarizine can precipitate or worsen these conditions). 1

Relative Contraindications

• Current depression (flunarizine may exacerbate depressive symptoms, particularly in the elderly). 1

Serious Adverse Effects

• Depression and extrapyramidal symptoms are the most concerning serious adverse effects, particularly in elderly patients. 1
• The American Psychiatric Association notes that depression is a significant risk with flunarizine use. 1
• The American Geriatrics Society warns that elderly patients are at increased risk for both depression and extrapyramidal symptoms. 1

Critical Pitfalls to Avoid

• Screen for depression and Parkinson's disease before initiating flunarizine, as it may exacerbate these conditions. 1
• Avoid flunarizine in elderly patients due to increased risk of extrapyramidal symptoms and depression. 1
• Do not use flunarizine as a first-line agent—ensure adequate trials of propranolol, timolol, or topiramate first. 1
• Limit acute medication use to ≤2 days per week to prevent medication-overuse headache from interfering with preventive therapy. 1
• Do not discontinue preventive therapy prematurely—an adequate trial requires 2–3 months at the target dose before assessing response. 1

Availability in the United States

• Flunarizine is not licensed or available in the United States. 3
• It is widely used in Europe and other regions, with extensive evidence supporting its efficacy. 2, 6, 3
• The National Institute for Clinical Excellence (UK) published supportive guidelines for flunarizine use in migraine in 2014, based on randomized controlled evidence. 3

Special Populations

• Flunarizine appears effective in children for migraine prophylaxis. 2, 6
• In chronic migraine, flunarizine was the most common indication in the UK cohort, followed by migraine with aura, hemiplegic migraine, and new daily persistent headache with migrainous features. 3