乌鸦传媒

Drugs and supplements showed nearly no effect in preventing pediatric migraine in a network meta-analysis that compared head-to-head and placebo-controlled trials.

Data from more than 2,200 children and adolescents showed that no migraine medication had a significant long-term effect lasting 5 to 6 months or longer, reported Joe Kossowsky, PhD, MMSc, of Boston Children's Hospital and Harvard Medical School, and colleagues.

Short-term improvements of less than 5 months were seen with propranolol (standard mean difference 0.60, 95% CI 0.03-1.17) and topiramate (Topamax; SMD 0.59, 95% CI 0.03-1.15), but the 95% prediction intervals for these medications contained the null effect, they wrote in .

"Migraine is an important problem; it's one of the most common neurological disorders in childhood," Kossowsky said. "While prophylactic medications are prescribed, remarkably little evidence is available regarding which ones work and their potential side effects."

The FDA has approved and triptan products for acute pediatric migraine, but in clinical practice. "Previous meta-analyses, which looked at how effective medications were compared with placebo, were not able to take into account studies directly comparing medications," Kossowsky told 乌鸦传媒. "Our analyses provide up-to-date rankings for the different medications used to prevent migraine with regard to their efficacy and safety, allowing providers to assess benefit versus risk for each medication and see how they compare to each other."

Network meta-analyses have been used to rate acute and preventive treatments in , noted Boris Zernikow, PhD, MD, of Witten/Herdecke University in Germany, in an . "For example, to address short-term treatment of migraine attacks, different triptans have been ranked, containing information on which triptan is most likely to gain a desired outcome (such as fast-action, low recurrence rate, or low frequency of adverse effects)," he wrote. But "key differences between children and adults in migraine presentation are evident" and research for pediatric patients "has been urgently needed," he added.

In their study, Kossowsky and colleagues looked at 23 double-blind clinical trials between through July 2018 that included 2,217 pediatric patients. Of these, 519 participants had been randomly assigned to placebo and 1,698 had been assigned either to anti-epileptics, antidepressants, calcium channel blockers, antihypertensive agents, or food supplements.

Trial participants had a diagnosis of episodic migraine, with or without aura, and were under age 18. Eligible trial designs included head-to-head comparisons of at least two agents and placebo-controlled trials. Primary outcomes were efficacy, safety, and acceptability of pediatric migraine treatment.

Participants had an average age of about 11 and 47% were girls. Short-term treatment had a median duration of 12 weeks. Most trials (nine of 23) recruited patients from Asia; six recruited from Europe, and five from North America.

Twelve treatments were assessed in the efficacy meta-analysis: L-5-hydroxytryptophan (5-HTP), pregabalin, propranolol, topiramate, cinnarizine, coenzyme Q10, riboflavin, sodium valproate, butterbur root extract, nimodipine (Nymalize), flunarizine, and placebo. Seven of these substances had been tested in fewer than 100 patients in the trials.

The efficacy analysis showed a significant short-term effect of propranolol and topiramate compared with placebo, but the 95% prediction interval for both of these studies was nonsignificant, the researchers said.

All other interventions had efficacy standard mean differences that were nonsignificant. Both pregabalin (SMD 0.81, 95% CI –0.28 to 1.90) and flunarizine (SMD 0.93, 95% CI −0.12 to 1.98) showed high standard mean differences versus placebo, but the findings were based on one study for each drug and were nonsignificant.

Safety and acceptability analyses showed no significant differences between any treatment and placebo.

While the results indicate potential for propranolol, topiramate, pregabalin, and flunarizine, they emphasize the need to identify which children are most likely to benefit and how long treatment should be, the researchers noted.

"We are moving forward with studies examining the effects of various genetic predispositions on medication efficacy in preventing migraine, which could hopefully allow for a more personalized medicine approach in the future," Kossowsky said. "At current, finding triggers and avoiding them, and maintaining good general health and a healthy lifestyle are key factors in preventing migraine episodes."

The network meta-analysis had several limits, Kossowsky and colleagues noted. Seven substances in the efficacy analysis were tested on fewer than 100 patients. Heterogeneity was substantial: doses, duration, and reporting methods varied widely. Only half of the trials reported dropouts due to adverse events. In addition, the within-study bias of many comparisons was assessed as moderate according to the framework, they added.

The findings reinforce the 2019 American Academy of Neurology (AAN) guidance for pediatric migraine prevention. In , guideline authors noted that most trials about preventive medications for pediatric migraine failed to demonstrate superiority to placebo and recommended counseling on lifestyle and behavioral factors that influence headache frequency.

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