Is there data supporting safety and efficacy of oral caffeine for pediatric migraine and at what dose?

Comment by InpharmD Researcher

Data assessing the use of oral caffeine for pediatric migraine management is limited and primarily derived from a small pilot trial (see Table 1). In this trial, ibuprofen combined with caffeine (50-100 mg) provided faster and greater pain relief compared to ibuprofen alone, though findings were not statistically significant. While caffeine may enhance analgesic efficacy when utilized as an adjunct in migraine management, its optimal dosing, safety, and overall efficacy in pediatric patients requires further investigation.

Background

A 2016 review article discussing the treatment of pediatric migraine highlights that acetaminophen and ibuprofen are the most commonly used over-the-counter options for pain relief and fever reduction in children. Both are effective and well tolerated, though ibuprofen is considered a better option for pain relief. However, the authors note that, based on their clinical experience, a combination of acetaminophen and a caffeine compound given at the onset of a migraine can provide faster and more effective relief than either agent alone. Ergot-based therapies, such as dihydroergotamine and ergotamine combined with caffeine, may also be beneficial during a migraine attack but should be used cautiously due to their vasoconstrictive effects; an angio-MRI may be considered before prescribing a caffeine-containing medication. Despite being a viable therapeutic agent, the authors emphasize that caffeine can still act as a migraine trigger, highlighting the importance of identifying and avoiding potential triggers. Of note, optimal caffeine dosing for pediatric patients was not specified in the review. [1]

Another review article discusses caffeine in headache management, highlighting its use in both adult and pediatric patients. Notably, only one study was referenced for pediatric use (see Table 1). In this study, ibuprofen-caffeine combinations were compared to ibuprofen alone in children with migraine or tension-type headache. Although limited by sample size and without statistically significant results, the combination showed faster and greater pain relief, with nearly 60% of children experiencing meaningful benefit. Overall, the authors note that caffeine is widely consumed and has important medical uses, mainly as an adjuvant in combination with analgesics for acute treatment of tension-type headache and migraine. However, further research is needed to better define its role and optimal dosing, particularly in pediatric populations. [2]

References:

[1] Teleanu RI, Vladacenco O, Teleanu DM, Epure DA. Treatment of Pediatric Migraine: a Review. Maedica (Bucur). 2016;11(2):136-143.
[2] Lipton RB, Diener HC, Robbins MS, Garas SY, Patel K. Caffeine in the management of patients with headache. J Headache Pain. 2017;18(1):107. Published 2017 Oct 24. doi:10.1186/s10194-017-0806-2

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there data supporting safety and efficacy of oral caffeine for pediatric migraine and at what dose?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Table 1 for your response.


 

Caffeine as an Adjuvant to Ibuprofen in Treating Childhood Headaches

Design

Double-blind cross-over pilot study

N= 12

Objective

To evaluate the effect of ibuprofen and caffeine compared with ibuprofen and placebo in children with headaches

Study Groups

Ibuprofen and caffeine (n= 12)

Ibuprofen and placebo (n= 12)

Inclusion Criteria

Patients less than 16 years of age with one or more migraine or episodic tension-type headaches per month, diagnosed according to International Headache Society revised criteria

Exclusion Criteria

Unable to swallow study capsules, on other medications for headaches or epilepsy, history of renal, hepatic or cardiovascular disease, asthma or coagulopathy, allergy to ibuprofen or caffeine, unable to complete the study protocol

Methods

Randomized double-blind, placebo-controlled study. Patients were required to treat two different headaches: one with ibuprofen (100-400 mg) and caffeine (50-100 mg), and the other with ibuprofen and placebo. Headache diaries were kept, recording severity and associated symptoms every 30 minutes up to 120 minutes

Medication dosing was as follows: 5-15 kg = 100 mg ibuprofen, 50 mg caffeine; 16-25 kg = 200 mg ibuprofen, 50 mg caffeine; 26-35 kg = 300 mg ibuprofen, 100 mg caffeine; > 35 kg = 400 mg ibuprofen, 100 mg caffeine

Duration

Not specified

Outcome Measures

Primary: Headache relief defined as a reduction in headache severity of ≥2 grades on the faces scale or severity levels

Secondary: Cumulative response scores at 30, 60, and 90 minutes

Baseline Characteristics

 

All patients (n= 12)

Age, years

11.9 (7-15)   

Female

58%

Headache type

          Migraine without aura

          Tension-type

 

75%

25%   

Results

Endpoint*

Ibuprofen and caffeine (n=12)

Ibuprofen and placebo (n=12)

Headache severity before treatment

3.8 4

Headache severity at 30 minutes

2.8 3.8

Headache severity at 60 minutes

2.3  3.1 
Time to reach severity level 1 or less, minutes 60 120 

* All values reported as means

Comparison of the cumulative response scores for the outcome measures revealed a trend toward a greater response to the ibuprofen-caffeine treatment (p = 0.14, 0.09, 0.07)

Adverse Events

Not specified

Study Author Conclusions

Caffeine may be an effective adjuvant to ibuprofen in children, as it is in adults, and there may be a subpopulation of adolescents who will benefit from this therapy. Further larger studies are needed to confirm this effect and identify potential responders.

InpharmD Researcher Critique

The study was a small pilot with only 12 participants, which limits the statistical power and generalizability of the findings. The trend towards significance suggests potential benefits, but larger studies are needed to confirm these results and identify specific responders. The study's crossover design is a strength, allowing each participant to serve as their own control.



References:

Dooley JM, Gordon KE, Wood EP, Brna PM, MacSween J, Fraser A. Caffeine as an adjuvant to ibuprofen in treating childhood headaches. Pediatr Neurol. 2007;37(1):42-46. doi:10.1016/j.pediatrneurol.2007.02.016