Topiramate, Pregabalin Reduce Headache Frequency, Intensity in Pediatric Migraine

A recent study showed that topiramate and pregabalin among children and adolescents were linked to reduced headache frequency and intensity.¹

“This comprehensive [network meta-analysis] sheds light on the pharmacological management of pediatric migraine, revealing that treatments like pregabalin, topiramate (with and without vitamin D3 supplementation), levetiracetam, flunarizine, riboflavin, amitriptyline, and cinnarizine may reduce migraine frequency in pediatric patients,” wrote investigators, led by Omid Kohandel Gargari, MD, from the headache department at the Iranian Center of Neurological Research, Tehran University of Medical Sciences.

Approximately 11% of children and adolescents live with migraine.² The incidence of migraine grows for people ≥ 14 years old and is more prevalent among females.3 Experiencing migraine headaches hinders the quality of life and academic performance among children and adolescents, hence the importance of assessing the efficacy and safety of pharmacological interventions for migraine prevention in this population.¹

Investigators conducted a network meta-analysis from December 2023 to March 2024 to assess pharmacological treatments' efficacy, safety, and acceptability for pediatric migraine prophylaxis. The team compared various oral pharmacological interventions with each other and placebo.

Leveraging data from PubMed, Embase, and SCOPUS (from inception up to September 2023), investigators included 45 randomized clinical trials that examined an oral pharmacological intervention for migraine and had a pediatric patient population (n = 3771).

The primary outcome was migraine frequency, defined as the number of attacks per month. Secondary outcomes included a ≥ 50% response rate, headache duration, headache intensity, and disability evaluated by the pediatrics migraine-specific disability tool). The team also evaluated for adverse events.

The analysis showed pregabalin (ratio of means [RoM], 0.38; 95% confidence interval [CI], 0.18 – 0.79) and topiramate with vitamin D3 (RoM, 0.44; 95% CI, 0.30 – 0.65) were linked to a reduction in migraine frequency, compared with placebo.

“Our research further explores an innovative analysis of combination therapies, emphasizing that the integration of supplements like vitamin D3 and riboflavin substantially augments the effectiveness of pregabalin,” investigators wrote.

The analysis showed pregabalin resulted in a 63% reduction in migraine frequency but taking it in conjunction with vitamin D supplementation may reduce headache frequency by 88%.

The medications lunarizine (RoM, 0.46; 95% CI, 0.26 – 0.81), levetiracetam (RoM, 0.47; 95% CI, 0.30 – 0.72), riboflavin (RoM, 0.50; 95% CI, 0.32 – 0.77), cinnarizine (RoM, 0.64; 95% CI, 0.46 – 0.88), topiramate (RoM, 0.70; 95% CI, 0.55 – 0.89), and amitriptyline (RoM, 0.73; 95% CI, 0.54 – 0.97) were also linked to a reduction in migraine frequency, but these findings were drawn from separate studies.

The drugs that had a ≥ 50% response rate, and thus associated with significantly greater effectiveness than placebo, included flunarizine and α-lipoic acid (risk ratio [RR], 8.73; 95% CI, 2.44 – 31.20), flunarizine (RR, 4.00; 95% CI, 1.38 – 11.55), pregabalin (RR, 1.88; 95% CI, 1.13 – 3.14), and cinnarizine (RR, 1.46; 95% CI, 1.04 – 2.05).

“Although there were also other drugs that showed statistically significant results (flunarizine, riboflavin, amitriptyline, and cinnarizine), more studies were required for a robust conclusion,” investigators wrote.

Moreover, no pharmacological interventions were associated with significant improvements in quality of life or reduction of migraine attack duration. Investigators wrote how these underscores the complexity of treating pediatric migraine and future research is needed to explore other treatment options.

The treatments with the greatest adverse events included amitriptyline (RR, 3.81; 95% CI, 1.41 – 10.32), topiramate (RR, 4.34; 95% CI, 1.60 – 11.75), and valproate (RR, 5.93; 95% CI, 1.93 – 18.23), compared with placebo.

“The study underscores the potential benefits of combination therapies, particularly those involving vitamin supplementation, and emphasizes the importance of larger, randomized clinical trials to confirm these findings and explore new avenues for enhancing care in pediatric migraine management,” investigators concluded.

References

1. ^{Kohandel Gargari O, Aghajanian S, Togha M, et al. Preventive Medications in Pediatric Migraine: A Network Meta-Analysis. JAMA Netw Open. 2024;7(10):e2438666. doi:10.1001/jamanetworkopen.2024.38666}
2. ^{Onofri A, Pensato U, Rosignoli C, et al. Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis. J Headache Pain. 2023;24(1):8. Published 2023 Feb 14. doi:10.1186/s10194-023-01541-0}
3. ^{Abu-Arafeh I, Razak S, Sivaraman B, Graham C. Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies. Dev Med Child Neurol. 2010;52(12):1088-1097. doi:10.1111/j.1469-8749.2010.03793.x}