Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis

Abstract

Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. Reduction in mean attack frequency was estimated by calculating the mean difference (MD), and a series of secondary outcomes—including adverse events (AEs)—were also analyzed. The database search yielded 879 unique records. Twenty-five studies were included in data synthesis. We scored 31/175 risk of bias items as “high,” with attrition as the most frequent bias. A pooled analysis estimated that flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo (5 trials, 249 participants: MD −0.44; 95% confidence interval −0.61 to −0.26). Analysis also revealed that the effectiveness of flunarizine prophylaxis is comparable with that of propranolol (7 trials, 1151 participants, MD −0.08; 95% confidence interval −0.34 to 0.18). Flunarizine also seems to be effective in children. The most frequent AEs were sedation and weight increase. Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10-mg flunarizine per day is effective and well tolerated in treating episodic migraine—supporting current guideline recommendations.

Oral Chinese Herbal Medicine as Prophylactic Treatment for Episodic Migraine in Adults: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…One case of decreased platelet count was reported, but there was not a confirmed association between this event and CHM [55]. Weight gain and ataxia were only reported in the flunarizine group, which agrees with previous research results on flunarizine [15,16,18,24,81,82]. Considering that aging [81,[83][84][85] and increased dosage [11,40,86,87] of flunarizine and the predisposing factors for its side effects, CHM could be an alternative for elderly patients and those who suffer from common side effects of flunarizine.…”

“…Flunarizine is a first-line medication recommended by clinical guidelines for migraine prophylaxis [10][11][12][13]. Its effects of preventing migraine attacks in adults have been confirmed by recently published systematic reviews [14,15], clinical trials [16][17][18], and experimental studies [19][20][21][22][23]. However, unwanted adverse effects such as tiredness, mood swings, weight gain, and depression limit its use in clinical practice [16,24].…”

Flunarizine Induced Parkinsonism in Migraine Group: A Nationwide Population-Based Study

“…For adult migraine, Fz is considered the first-line prophylactic choice as per several guidelines (Pringsheim et al, 2012;Silberstein et al, 2012;Charles, 2017). A meta-analysis estimated that Fz reduces the headache frequency by 0.4 attacks per 4 weeks (Stubberud et al, 2019). Fz also improves the clocking tinnitus in migraine patients (Chen et al, 2019).…”

Reference programme: diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 3rd edition, 2020

“…Treatment with beta-blockers (propranolol or metoprolol) and flunarizine has a comparable preventive effect in children and adolescents [87,88]. The effect of beta-blockers has been documented in a single RCT and flunarizine in a single randomized study [87,88]. There are need more RCTs to document an effect of beta-blockers and flunarizine.…”