Dexamethasone Fails to Reduce Migraine Relapse in Pediatric ED Population, Trial Shows

In a recently published randomized, double-blind, placebo-controlled trial, investigators evaluated whether adjunctive intravenous dexamethasone could reduce relapse rates in pediatric patients presenting to the emergency department with acute migraine. Results showed that adjunctive dexamethasone did not reduce relapse rates or improve functional outcomes compared with placebo, raising questions about its continued routine use in this population.¹

Led by Geneviève Tourigny-Ruel MD, MBA, pediatric urgent care physician at CSU Saint-Justine in Montreal, the trial enrolled 116 patients aged 8 to 17 years who required intravenous rescue therapy for acute migraine. Conducted at a tertiary pediatric ED in Canada, all participants received standard abortive treatment with metoclopramide and diphenhydramine and were discharged on a 48-hour course of naproxen. Patients were randomized to receive either a single dose of intravenous dexamethasone (0.6 mg/kg; maximum 15 mg) or placebo prior to discharge. The primary endpoint was relapse within 48 hours, defined as recurrence or worsening of headache following initial improvement.¹

Among the 87 patients (75%) who provided outcome data at 48 hours, relapse occurred in 39% of those treated with dexamethasone compared with 44% in the placebo group, corresponding to a nonsignificant risk difference of −4% (95% CI, −32% to 24%). Secondary outcomes, including pain scores assessed by visual analog scale (VAS) and verbal numeric scale (VNS), return to school or normal activities, and health care utilization, also did not differ significantly between groups. At 48 hours, fewer than half of participants in either arm had returned to school, underscoring the short-term functional burden of migraine in this population.¹

Pain outcomes remained similar between groups at both 48 hours and 7 days postdischarge, with both cohorts demonstrating gradual improvement over time. Notably, a high proportion of patients in both groups required additional medications, including naproxen and acetaminophen, during follow-up, highlighting the continued need for symptomatic management after ED discharge. Investigators noted that dexamethasone is often administered upfront in clinical practice; however, the findings of this study specifically apply to patients who had already responded to initial abortive therapy.

Adverse events were infrequent and mild across both treatment arms, with no major safety concerns identified. Reported symptoms included abdominal pain, dizziness, and throat discomfort, with no statistically significant differences between groups. Although the safety profile of single-dose dexamethasone appeared acceptable, the absence of demonstrated efficacy raised questions about its routine use in pediatric migraine management.

The findings contrast with prior adult data, including a meta-analysis of randomized trials showing a modest reduction in relapse risk with dexamethasone (relative risk, 0.87; 95% CI, 0.80–0.95). However, the investigators emphasized that such findings may not be generalizable to pediatric populations, given differences in migraine pathophysiology, treatment response, and developmental factors. To their knowledge, this study represents the first randomized controlled trial to directly evaluate dexamethasone for migraine relapse prevention in children and adolescents.¹

Several limitations may have influenced the results. The study did not reach its planned sample size, and approximately 25% of enrolled participants were lost to follow-up, reducing statistical power and increasing the risk of type II error. Sensitivity analyses using best- and worst-case imputation scenarios produced divergent results, further underscoring the uncertainty around the true effect size. Additionally, reliance on patient-reported outcomes and the single-center design may limit generalizability.¹

Despite these limitations, the trial provides important evidence suggesting that adjunctive dexamethasone does not confer meaningful benefit in reducing relapse or improving functional recovery in pediatric patients treated for acute migraine in the ED. The authors concluded that routine use of corticosteroids in this setting may not be warranted, particularly given the lack of efficacy and the potential for cumulative adverse effects with repeated exposure.

Future research is needed to identify subgroups of pediatric patients who may benefit from corticosteroid therapy, as well as to explore alternative strategies for relapse prevention. These may include optimized nonsteroidal anti-inflammatory regimens, triptan use, and behavioral interventions aimed at reducing recurrence and improving quality of life. Until such data are available, clinicians may consider a more selective approach to corticosteroid use in children and adolescents with migraine.

Dexamethasone has also been evaluated in other neurologic conditions, with similarly mixed results. Topline results from the phase 3 NEAT trial showed that dexamethasone sodium phosphate encapsulated in autologous erythrocytes (EryDex; Quince Therapeutics) did not significantly improve neurologic outcomes compared with placebo in children and adolescents with ataxia-telangiectasia (A-T) over 6 months of treatment. Although the investigational therapy was generally well tolerated, the findings underscored the ongoing challenges in identifying effective disease-modifying treatments for A-T.²

The NEAT study (NCT06193200) was an international, multicenter, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 105 participants with genetically confirmed A-T across sites in the United States, United Kingdom, and Europe. Participants were randomized 1:1 to receive either EryDex or placebo infusions administered every 21 to 30 days for a total of six infusions over approximately 6 months.²

According to the topline data, the mean change from baseline to month 6 on the Rescored modified International Cooperative Ataxia Rating Scale (RmICARS) was 0.94 in the active-treatment arm compared with 2.24 in the placebo arm, corresponding to a treatment difference of −1.30 that did not reach statistical significance (P = .0851). The trial also failed to meet its key secondary endpoint of improvement on the Clinical Global Impression of Severity (CGI-S) scale (P = .522).

REFERENCES
1. Tourigny-Ruel G, Bailey B, Jean-Charles S, Gravel J. Dexamethasone for prevention of migraine relapse in children and adolescents treated in the emergency department: a randomized clinical trial. Headache. Published online 2025. doi:10.1111/head.70087
2. Trouillas P, Takayanagi T, Hallett M, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci. 1997;145(2):205-211. https://doi.org/10.1016/S0022-510X(96)00231-6