Objectives: To assess the comparative effectiveness and safety of preventive pharmacologic treatments for community-dwelling children with episodic or chronic migraine.
Data sources: We searched major electronic bibliographic databases, including Medline® and Cochrane Central Register of Controlled Trials, and trial registries up to May 20, 2012.
Review methods: We performed a systematic review of original studies published in English that examined episodic or chronic migraine and rates of complete cessation or reduction of monthly migraine frequency by ≥50 percent, reduction in migraine-related disability, and improvement in quality of life with off-label drugs. (No preventive drugs were approved in children.) Also eligible were studies that compared drugs with nonpharmacologic interventions or drug management programs. We calculated absolute risk differences, pooled them with random-effects models, and calculated numbers of outcome events attributable to treatment effects per 1,000 treated.
Results: Prevention of episodic migraine in children was examined in 24 publications of randomized controlled trials (RCTs) that enrolled 1,578 children and in 16 nonrandomized studies. Evidence was low strength due to risk of bias and imprecision. Propranolol was estimated to result in complete cessation of migraine attacks in 713 per 1,000 children treated (95-percent confidence interval [CI], 452 to 974) (one RCT). Trazodone (one RCT) and nimodipine (one RCT) decreased migraine days more effectively than placebo. Topiramate (two RCTs), divalproex (one RCT), and clonidine (one RCT) were no more effective than placebo in preventing migraine. Sodium valproate demonstrated no significant differences for migraine prevention or migraine-related disability compared with propranolol (two RCTs) or topiramate (one RCT). Metoprolol tended to be less effective than stress management in preventing migraine or reducing migraine severity (one RCT). Propranolol had less effect than self-hypnosis on absolute number of migraine attacks (one RCT). Multidisciplinary drug management was more effective than usual care in preventing migraine in children and adolescents (one RCT), but the effect was not sustained at 6 months. Divalproex sodium (one RCT) resulted in treatment discontinuation due to adverse effects more often than placebo. Treatment discontinuation due to adverse effects did not differ between topiramate (two RCTs), trazodone (one RCT), propranolol (one RCT), or clonidine (one RCT) and placebo. Topiramate increased risk of paresthesia, upper respiratory tract infection, and weight loss. No RCTs examined prevention of chronic migraine in children.
Conclusions: Limited low-strength evidence suggests that propranolol was more effective than placebo for preventing episodic migraine in children, with no bothersome adverse effects that could lead to treatment discontinuation. Long-term preventive benefits are unknown both for drugs and nonpharmacologic interventions. No studies examined quality of life or provided evidence for individualized treatment decisions. Future randomized trials of drugs with favorable benefits-to-harms ratio in adults are needed to identify effective and safe treatments to prevent episodic and chronic migraine in children.