Question 1: In children presenting with acute migraine, what appears to be the best abortive pharmacological treatment?

A 2004 randomized controlled trial compared IV ketorolac (0.5 mg/kg, maximum 30 mg) and IV prochlorperazine (0.15 mg/kg, maximum 10 mg) in 62 children (ages 5–18 years) with migraine presenting to two pediatric emergency departments.¹ All children received a normal saline IV fluid bolus as well. Treatment success was defined as ≥50 percent reduction in pain score at one hour as measured by the Nine Faces Pain Scale. If the child’s headache did not improve by ≥50 percent at one hour, then the child received the other study medication and treatment success was measured again one hour later.

In the prochlorperazine (n=33) and ketorolac (n=29) groups at one hour, treatment success was 84.8 percent (28 of 33 children) and 55.2 percent (16 of 29 children), respectively, suggesting that prochlorperazine was better at providing successful migraine relief at one hour. Overall success—defined as either ≥50 percent reduction after a single medication at one hour or ≥50 percent reduction after receiving both medications at two hours—was 93.3 percent (56 of 60 children). This suggests that the combination of both prochlorperazine and ketorolac is more successful at reducing pain than either alone.

Similar results for combination therapy were seen in a 2021 prospective observational study that evaluated 120 children (ages 7–18 years) with migraine with standard combination therapy containing IV ketorolac (0.5 mg/kg, maximum 30 mg), IV prochlorperazine (0.15 mg/kg, maximum 10 mg), and IV diphenhydramine (1 mg/kg, maximum 50 mg).² The authors’ primary aim was to evaluate headache severity at two hours, 24 hours, and seven days after administration. Compared to premedication pain assessment, at two hours, 24 hours, and seven days, the median reduction in pain score was 87.5 percent, 100 percent, and 50 percent (P=0.001), respectively, suggesting that combination therapy was effective at treating pediatric migraine. Of note, this study only included the dopamine receptor antagonist prochlorperazine. As in adults, it appears that migraine combination therapy in children significantly reduces migraine pain scores.

But which dopamine receptor blocker is best studied in pediatric migraine? There are few studies comparing dopamine receptor blockers. Most have evaluated prochlorperazine. A 2015 study retrospectively evaluated 32,124 children ages 7–18 years with migraine across 35 children’s hospitals.³ The primary outcome was 72-hour ED return visit for any reason in patients who were initially discharged from the emergency department. Of the 32,124 patients presenting with migraine to the emergency department, 85 percent were discharged and eligible for the outcome analysis. The authors examined the most common medications administered at the initial ED evaluation for the patient’s migraine including nonopioid analgesics (65.6 percent), dopamine receptor antagonists (49.9 percent), and diphenhydramine (33.2 percent). Among discharged patients, 5.5 percent had a return visit within 72 hours. Compared to prochlorperazine, children receiving metoclopramide had an adjusted odds ratio of 1.31 (95 percent confidence interval [CI] 1.11–1.55) for 72-hour ED return, suggesting that prochlorperazine might be better for treatment of migraine in children compared to metoclopramide.

A separate 2018 retrospective study evaluated prochlorperazine (n=27), metoclopramide (n=23), and promethazine (n=17) for their efficacy in aborting a migraine.⁴ This study included 67 children under 19 years of age. All patients additionally received IV ketorolac. No dosing concentrations were mentioned in the study, which is one of its biggest weaknesses. Outcomes included treatment failure, return visits within 48 hours, and pain score. Treatment failures were 8.7 percent with prochlorperazine, 25 percent with metoclopramide, and 43 percent with promethazine. There was no significant difference in return visits at 48 hours.

Summary

Prochlorperazine (0.15 mg/kg) is the most commonly studied and most effective intravenous abortive migraine therapy in children. Combination therapy with ketorolac (0.5 mg/kg) appears to improve success. Plus-circle

References

1. Brousseau DC, Duffy SJ, Anderson AC, et al. Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med. 2004;43(2):256-262.
2. Kannikeswaran N, Desai L, Farooqi A, et al. Effectiveness of standard combination therapy in pediatric migraine. Pediatric Neurol. 2021;116:68-73.
3. Bachur RG, Monuteaux MC, Neuman MI. A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics. 2015;135(2):232-238.
4. Sheridan DC, Laurie A, Pacheco S, et al. Relative effectiveness of dopamine antagonists for pediatric migraine in the emergency department. Pediatr Emerg Care. 2018;34(3):165-168.
5. Orr SL, Kabbouche MA, Horn PS, et al. Predictors of first-line treatment success in children and adolescents visiting and infusion center for acute migraine. Headache. 2018;58(8):1194-1202.