Amitriptyline and topiramate, the most commonly used medications for preventing pediatric migraine, are no more effective than placebo, according to trial results published online ahead of print October 27 in the New England Journal of Medicine. The drugs are, however, associated with higher rates of adverse events.
While the researchers were conducting this study, the FDA approved topiramate for the treatment of episodic migraine in adolescents between ages 12 and 17. “Although our trial included patients outside this age range and included those with either episodic or chronic migraine, the trial results suggest that prevention medication for pediatric migraine might be reexamined,” said Scott W. Powers, PhD, Codirector of the Headache Center at Cincinnati Children’s, and colleagues.
Scott W. Powers, PhD
The FDA has not approved any migraine-prevention medication for children younger than 12, and clinical practice guidelines for this indication are based on consensus, rather than evidence. Dr. Powers and colleagues conducted the Childhood and Adolescent Migraine Prevention (CHAMP) trial to compare the efficacy of common medications in children and adolescents between ages 8 and 17 with migraine. They randomized 361 patients to amitriptyline (1 mg/kg/day), topiramate (2 mg/kg/day), or placebo in a 2:2:1 ratio.
The trial included a 28-day baseline period, an eight-week dose-escalation period, and a 16-week maintenance phase. The primary outcome was a reduction of 50% or more in the number of headache days during the last 28 days of the trial, compared with baseline. Secondary outcomes included headache-related disability, headache days, number of trial completers, and serious adverse events.
The baseline characteristics of the three treatment groups were similar. The population’s mean age was 14. About 68% of the population was female, and 70% was white.
After a planned interim analysis, the investigators ended the trial early for futility. They found no significant between-group differences in the primary outcome. Approximately 52% of patients receiving amitriptyline, 55% of those receiving topiramate, and 61% of controls had a reduction in headache days of at least 50%. Headache-related disability, headache days, and the rate of trial completion also did not differ between groups.
Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs 14%) and dry mouth (25% vs 12%) in the amitriptyline group and paresthesia (31% vs 8%) and weight loss (8% vs 0%) in the topiramate group. Three patients receiving amitriptyline had serious adverse events of altered mood, and one patient receiving topiramate attempted suicide.
“We see this [study] as an important opportunity for health care providers, scientists, children, and families because our findings suggest a paradigm shift,” said Dr. Powers. “First-line prevention treatment will involve a multidisciplinary team approach and focus on nonpharmacologic aspects of care. The good news is we can help children with migraines get better.”
—Erik Greb
Suggested Reading
Powers SW, Coffey CS, Chamberlin LA, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2016 Oct 27 [Epub ahead of print].