Does flunarizine provide migraine prophylaxis?

Flunarizine for Migraine Prophylaxis

Flunarizine is an effective second-line agent for migraine prophylaxis, reducing attack frequency by approximately 0.4 attacks per 4 weeks compared to placebo, with efficacy comparable to propranolol. 1, 2

Position in Treatment Algorithm

Flunarizine should be considered after failure or intolerance of first-line agents (propranolol, timolol, topiramate, or candesartan), but before escalating to third-line CGRP monoclonal antibodies or onabotulinumtoxinA. 1

• First-line preventive medications include propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (50-100 mg/day), and candesartan, all with strong evidence for episodic migraine prevention 3, 1
• Flunarizine (5-10 mg once daily at night) is positioned as an effective second-line option where available, with proven efficacy comparable to propranolol and topiramate 1, 2
• Third-line options include CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) after failure of 2-3 oral preventive medications 3, 1

Evidence for Efficacy

The evidence supporting flunarizine is robust, though the medication is not available in the United States:

• Meta-analysis of 5 placebo-controlled trials (249 participants) demonstrated flunarizine reduces headache frequency by 0.44 attacks per 4 weeks (95% CI: -0.61 to -0.26). 2
• Comparative trials (7 studies, 1151 participants) show flunarizine effectiveness is equivalent to propranolol, with no significant difference in attack reduction (MD -0.08; 95% CI -0.34 to 0.18). 2, 4
• One placebo-controlled study in classical migraine showed an 82% reduction in a corrected migraine index (frequency, duration, severity) versus a 66% increase in placebo patients 5
• Direct comparison with propranolol showed 67% of flunarizine patients responded positively versus 51% of propranolol patients, with significantly greater decrease in attack frequency at 1 and 4 months 4

Dosing and Implementation

Start flunarizine at 5-10 mg once daily, taken at night to minimize daytime sedation, and allow a 2-3 month trial period before assessing efficacy. 1

• Standard dosing is 10 mg once daily at night, which is the most commonly studied and used dose 1, 2
• Alternative dose of 5 mg once daily can be used for patients concerned about side effects, particularly weight gain or sedation 1
• Clinical benefits may not become apparent for 2-3 months, requiring an adequate trial period before declaring treatment failure 3, 1
• Track attack frequency, severity, and disability using headache diaries, and assess for side effects at follow-up visits within 2-3 months 1

Adverse Effects and Safety Profile

Common adverse effects include sedation/daytime tiredness (minimized by nighttime dosing), weight gain, and abdominal pain; serious adverse effects include depression and extrapyramidal symptoms, particularly in elderly patients. 1

• Most frequent adverse events are sedation and weight increase, though reporting of adverse events was inconsistent across trials 2, 4
• Propranolol significantly reduced blood pressure and heart rate, while flunarizine had no effect on cardiovascular function, potentially offering a better safety profile 4
• In rare cases, depressive mood and extrapyramidal motor disorders have been reported 6
• One study reported no side effects occurred during treatment 5

Contraindications and Precautions

Absolute contraindications include active Parkinsonism or history of extrapyramidal disorders; current depression is a relative contraindication. 1

• 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
• Unlike propranolol, flunarizine has no cardiovascular contraindications (no effect on blood pressure or heart rate) 4

Critical Pitfalls to Avoid

• Do not use flunarizine as first-line therapy—propranolol, timolol, topiramate, or candesartan should be tried first based on current guideline recommendations 3, 1
• Do not assess efficacy before 2-3 months of treatment—one case illustrated that flunarizine may require at least 4 months before efficacy can be judged 5
• Do not prescribe to elderly patients without careful consideration—increased risk of extrapyramidal symptoms and depression in this population 1
• Do not initiate in patients with active depression or Parkinsonism—these are contraindications that must be screened for before starting therapy 1
• Do not forget to limit acute medication use to ≤2 days per week—medication overuse can interfere with preventive therapy effectiveness 1

Clinical Context

Flunarizine is recognized in multiple international guidelines as an effective migraine preventive but is not available in the United States 3. The 2003 AAFP/ACP-ASIM guidelines note it as an agent with proven efficacy but currently unavailable in the U.S. 3. Where available internationally, it represents a valuable second-line option with a potentially better safety profile than propranolol, particularly for patients with cardiovascular concerns 4.