Prophylactic Treatments Have Minimal Effect in Pediatric Migraine

Karin Meissner, MD

Results from a network meta-analysis of prophylactic pharmacologic treatments demonstrated little evidence supporting efficacy in pediatric migraine compared with placebo.

Using Medline, Cochrane, Embase, and PyschINFO, investigators compiled data from 23 studies that examined preventive pharmacologic treatments in children and adolescents diagnosed with episodic migraine.

The investigators assessed efficacy outcomes including migraine frequency, number of migraine days, number of headache days, headache frequency, and headache index. Safety and tolerability outcomes such as discontinuations from adverse events and treatment discontinuation for any reason were recorded, as well.

The 23 studies included comprised of 2217 patients and were conducted between 1974 and 2018. Overall, 13 pharmacologic treatments were compared with placebo, including cinnarizine, pregabalin, propranolol, sodium valproate, topiramate, flunarizine, coenzyme Q10, L-5-hydroxytryotopham, riboflavin, nimodipine, and butterbur root extract.

Of the 2217 participants assessed, 1698 were randomly assigned to active drugs and 519 were assigned to placebo. Patients who had either migraine with or without aura were included in most of the trials (14 trials; 61%). The median duration of short-term treatment was 12 weeks (range, 4-24 weeks), while the mean (SD) age of participants was 10.9 years (2.41).

READ MORE: Pediatric Migraine Guidelines Provide Framework for Disease Management

When assessing short-term efficacy, propranolol had a standardized mean difference (SMD) of 0.60 (95% CI, 0.03-1.17) while topiramate had a standardized mean difference of 0.59 (95% CI, 0.03-1.15). These were among the only 2 treatments that were significantly more effective than placebo. All other treatments showed a nonsignificant standardized mean difference, ranging from -0.21 (95% CI, -1.40 to 0.99) for L-5-hydroxytryotopham to 0.93 (95% CI, -0.12 to 1.98) for flunarizine.

No treatments were significantly more effective than placebo in the long-term analysis.

“Future research could identify factors associated with individual responses to pharmacological prophylaxis, analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and identify nonpharmacologic targets for migraine prophylaxis,” the study authors concluded.

Addressing recently updated guidelines for the design of clinical trials for pediatric migraine, Andrew Hershey, MD, PhD, director of the division of neurology and a headache medicine specialist at Cincinnati Children’s Hospital, and professor of pediatrics at the University of Cincinnati College of Medicine, commented that prevention strategies in this population are particularly complex.

"The best evidence from the guidelines is the combination of cognitive-behavioral therapy and amitriptyline, while the evidence of traditional preventive agents remains less robust (i.e., amitriptyline alone, topiramate, divalproate, propranolol). Although it was not recommended against these treatments, a more holistic approach that uses a multidisciplinary team and inclusion of healthy habits appears to have the strongest benefit," he told NeurologyLive at the time. Hershey, one of the senior investigators of the CHAMP clinical trial, whose findings were echoed in this meta-analysis, further expressed the necessity of a multidisciplinary approach to treating migraine in the pediatric population and better-designed clinical trials with enough power to demonstate clinically meaningful treatment effect.

"Since 2004, there have been additional studies of the efficacy of acute and preventive treatments for migraine in children and adolescent that has included approval for these treatments by the US FDA and the EMA. The use of a multidisciplinary approach is becoming clearer with a combination of acute, preventive and biobehavioral therapy," he told NeurologyLive. T"he guidelines also continue to identify the complexity of developing the studies to prove efficacy as children’s and adolescent’s studies follow the results of adult studies such that there is a much higher expectation of response and thus impact the placebo component. This has limited the impact of major changes and opens the door for new and novel research paradigms."

REFERENCE

Locher C, Kossowsky J, Koechlin H, et al. Efficacy, safety, and acceptability of pharmacologic treatments for pediatric migraine prophylaxis. JAMA Pediatr. Published online February 10, 2020. doi:10.1001/jamapediatrics.2019.5856.