Researchers Uncover Effectiveness of 2 Preventive Agents in Reducing Incidence, Severity of Pediatric Migraine

December 11, 2019

Two migraine prevention agents, cinnarizine and sodium valproate, were shown to be safe and effective in reducing incidence and severity of migraine within children and adolescents, according to study findings. Safety findings must be weighed alongside warnings from European regulators about the risks of valproate for girls and adolescent women who could bear children in the future.

Two migraine prevention agents, cinnarizine and sodium valproate, were shown to be safe and effective in reducing incidence and severity of migraine within children and adolescents, according to November study findings published in Cephalalgia.

Pediatric migraine is known to effect about 8% of children and adolescents, with nearly half of those affected continuing to experience symptoms into adulthood. Current recommendations for preventive pharmacologic treatment of migraine include when the frequency of headaches is more than 4 attacks per month or when quality of life, school attendance, or daily activities are limited.

Treating migraine through early diagnosis and interventions is crucial in diminishing the global burden of the condition. While studies have shown that migraine preventive treatment can decrease this burden, researchers noted that few of these medications have been assessed in the pediatric population.

However, valproate-containg medicines have been the subject of study by the European Medicines Agency, and last year its Coordination Group for Mutual Recognition and Decentralised Procedures endorsed steps to ban the medicines during pregnancy unless there is no other effective treatment. The EMA statement calls for patients to be fully fully informed of risks and warns, “Further, the medicines must not be used in any woman or girl able to have children unless the conditions of a new pregnancy prevention [program] are met.”

Researchers sought to evaluate the safety and efficacy of 2 drugs, cinnarizine, an antihistaminic medication used to relieve symptoms of motion sickness and balance disorders, and sodium valproate, an anticonvulsant drug approved for use in epilepsy and bipolar disorder with additional use for neuropathic pain and migraine, through a randomized double-blind placebo-controlled trial on 149 Iranian children and adolescents:

  • Participants randomly assigned at 1:1:1 ratio to receive cinnarizine (n = 49), sodium valproate (n = 51), or placebo (n = 49)
  • Primary end points were mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial
  • The secondary end point was efficacy of each drug in the prevention of migraine, with the drug being deemed effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline
  • The safety end point was measured by the adverse effects reported by children or their parents.

Study results exhibited a stark decrease in the frequency of migraine attacks compared with baseline in cinnarizine (difference, −8.0; 95% CI, −9.3 to −6.6), sodium valproate (difference, −8.3; 95% CI, −9.3 to −7.2), and placebo (difference, −4.4; 95% CI, −5.4 to −3.4), with statistically greater reductions in cinnarizine (difference, −3.6; 95% CI, −5.5 to −1.6) and sodium valproate (difference, −3.9; 95% CI, −5.8 to −1.9) compared with placebo.

For migraine severity, children of all groups exhibited significant reductions in intensity of episodes from baseline (cinnarizine, −4.6; 95% CI, −5.2 to −4.0; sodium valproate, −4.0; 95% CI, −4.8 to −3.3; placebo, −2.6; 95% CI, −3.4 to −1.8). Similar to that shown in frequency measurements, reductions were statistically more prominent in cinnarizine (difference, −2.0; 95% CI, −3.2 to −0.8) and sodium valproate (difference, −1.5; 95% CI, −2.7 to −0.3) compared with placebo.

The secondary end point of measuring patients reporting more than 50% reduction in migraine episodes at the end of the trial was shown to include 71% of patients receiving cinnarizine, 66% of those in the sodium valproate group, and 42% of those receiving placebo. Among the study cohort, 9 patients reported adverse effects (3 for cinnarizine, 5 for sodium valproate, and 1 for placebo), with 1 individual having to discontinue sodium valproate due to severe sedation.

Compared with placebo, the 2 preventive agents exhibited significant reductions in migraine incidence and severity, warranting further analyses into their efficacy among the global population. “Cinnarizine and sodium valproate may be useful for migraine preventive treatment for children and adolescents. Both medications are safe and well-tolerated in terms of adverse events, but cinnarizine could be considered as a new preventive option for pediatric migraine,” said the study authors.

Reference

Amanat M, Togha M, Agah E, et al. Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: a randomized double-blind placebo-controlled trial [published online November 10, 2019]. Cephalalgia. doi: 10.1177/0333102419888485.