Reducing Frequency of Pediatric Headaches

There are few trials examining prophylactic treatment of pediatric headaches; however, researchers found placebo treatment was associated with a significant decline in headaches each month. The drugs topiramate and trazodone showed limited efficacy as well [JAMA Pediatr. doi:10.1001/jamapediatrics.2013.508].

It is estimated that 15% of children and adolescents suffer from tension headaches and 4% from migraines. As with adults, the purpose of prophylactic treatment is to reduce the frequency or severity of headaches. Common options include antiepileptic drugs (topiramate, sodium valproate), antidepressants (trazodone, amitriptyline), antihistamines (cyproheptadine), calcium channel blockers (flunarizine), antihypertensive medications (propranolol), and nonsteroidal anti-inflammatory drugs (naproxen). Researchers recently conducted a meta-analysis to compare the effectiveness and adverse effects of various pharmacologic prophylactic treatments of headaches in children and adolescents.

The meta-analysis consisted of published, randomized, controlled trials that examined efficacy in reducing the frequency or severity of headaches in patients <18 years of age. Trials reporting on migraine, tension, or chronic daily headache, with either placebo or comparisons between ≥2 active medications, were eligible for inclusion. The primary outcome measure was the number of headaches per month, which was pooled using the DerSimonian and Laird random effects model. The researchers selected a time point of 12 weeks for the primary analysis, although they calculated pooled estimates for each drug at all time points reported. Placebo response was also evaluated by pooling the frequency of headaches at each time point among patients receiving placebo and comparing the data to the other treatment groups using random effects meta-regression.

A total of 21 articles were included in the final analysis. This included 13 placebo-controlled trials and 10 trials that compared at least 2 interventions (2 of which also included placebo). All but 1 of these trials examined episodic migraines (<15 headaches per month). The other trial examined chronic daily headaches (any headache type that occurred ≥15 or more times per month). Mean values included a study duration of 12 weeks, a sample size of 70, and age of 11.4 years. Less than half (46%) were girls. Among the 13 placebo-controlled trials, 2 evaluated clonidine; 1 flunarizine; 1 flunarizine and piracetam; 1 fluoxetine; 1 pizotifen; 3 propranolol; 2 topiramate; 1 trazodone; and 1 valproate. A mean of 82 patients participated in the placebo-controlled trials.

Results showed topiramate and trazodone reduced headache more than placebo for relief of episodic migraines (–0.71; 95% confidence interval [CI], –1.19 to –0.24; and –0.60; 95% CI, –1.09 to –0.11, respectively). The researchers found the following agents to be no more effective than placebo: clonidine, flunarizine, pizotifen, propranolol, and valproate. Results of one trial of fluoxetine found the drug ineffective. The researchers also noted that patients given placebo experienced a significant decline (P=.03) in headaches, from 5.6 headaches per month (95% CI, 4.52-6.77) to 2.9 headaches per month (95% CI, 1.66-4.08). All drugs were reported as generally well tolerated.

In active comparator trials, flunarizine was found more effective than piracetam in reducing headaches at 16 weeks (–2.20; 95% CI, –3.93 to –0.47). No differences in effectiveness were found among other comparisons. Results also showed that a 100-mg dose of topiramate was more likely to produce a 50% reduction in headaches than a dose of 50 mg (relative risk, 1.81; 95% CI, 1.23-2.68). The mean Jadad score among placebo-controlled trials was 4.3 (range, 1-8), with no relationship between Jadad scores and outcomes (P=.19).

The study had several limitations, which included the relatively few studies on prophylactic treatment of headaches among children and adolescents. None of the included trials assessed treatment of tension headaches or chronic migraines. Additionally, the data had considerable heterogeneity, the trials were relatively short in duration, and no unpublished data were included. The researchers concluded that more study of pediatric headaches is needed, with future trials including placebo controls.