Table 1.
Summary of studies on complementary and integrative medicines for pediatric migraine.
| Diet | References: Study Design | N/Patients | Intervention | Comparison | Outcomes | Adverse Effects |
|---|---|---|---|---|---|---|
| Riboflavin | Athaillah et al., 2012 [22]: RCT |
98 adolescents with migraine | Riboflavin (400 mg daily) for three months (n = 50) | Placebo for three months (n = 48) | Headache frequency was decreased from the 1st month (6.4 episodes/month) to the 2nd month (3.9) to the 3rd month (3.7 per month) and duration decreased (p = 0.012 and p = 0.001, respectively) vs. placebo. Disability, as measured by the PedMIDAS was also decreased (34.3 to 26.1; p = 0.001). | Polyuria (n = 18), and diarrhea (n = 12) |
| Talebian et al., 2018 [23]: RCT |
90 children and adolescents with migraine | Riboflavin (200 mg or 400 mg daily) for 3 months (n = 30, and 30, respectively) | Placebo for three months (n = 30) | The Riboflavin 400 mg group had a greater reduction in the headache frequency (9.3 to 2.9 episodes/month) and duration (7.9 to 3.9 episodes/month) as compared to placebo (p = 0.00 and p = 0.00, respectively). | None | |
| MacLennan et al., 2008 [24]: RCT | 48 children and adolescents with migraine | Riboflavin (200 mg daily) for 12 weeks (n = 27) | Placebo for 12 weeks (n = 21) | No difference between the groups in terms of the proportion of participants with 50% or greater reduction of migraine frequency (44.4% of the riboflavin vs. 66.6% of the placebo group, p = 0.125) | Change in urine color (n = 1) |
|
| Bruijn et al., 2010 [25]: Crossover RCT |
42 children with migraine | Riboflavin (50mg daily) for four months (n = 20) | Placebo for four months (n = 22) | No difference between groups in terms of change in migraine frequency (p = 0.44); the riboflavin group had a greater reduction in the frequency of tension-type headaches as compared to placebo (p = 0.04) | None | |
| Yamanaka et al., 2020 [26]: Retrospective observational study | 68 children and adolescents with migraine | Riboflavin (10 or 40 mg daily) for three months (n = 13, and 55, respectively) | N/A | Significant overall reduction in the median frequency of headache episodes from the baseline to three months (median, 5.2 vs. 4.0 respectively, p = 0.00) was shown. |
None | |
| Condo et al., 2009 [27]: Retrospective chart review |
41 children and adolescents with a variety of headache disorders | Riboflavin (200 mg or 400 mg daily) for three, four or six months | N/A | Significant reduction in headache frequency after treatment for three or four months (21.7_13.7 vs. 13.2_11.8, p < 0.01), which was not sustained at six months (19.3_13.4 vs. 11.4_9.6, p > 0.05) |
Vomiting (n = 1), increased appetite without weight gain (n = 1), and temporary yellow-orange coloration of urine (some patients) |
|
| Das et al., 2020 [28]: Retrospective observational study |
42 children and adolescents with a variety of headache disorders | Riboflavin (100 and 200 mg for children weighing 20 to 40 kg and greater than 40 kg, respectively) | N/A | There was a significant decrease in the number of headache days (frequency) after 2 to 4 months (11.07 ± 10.52 days) compared to baseline (21.90 ± 9.85 days). Mean headache intensity decreased from 8.85 ± 6.41 to 2.30 ± 2.51 (p < 0.001 on a scale of 0 to 10), and headache duration also decreased significantly from 18.23 ± 17.07 h to 10.18 ± 10.49 h; p < 0.001). | None | |
| Coenzyme Q10 | Hershey et al., 2007 [29]: Prospective open-labeled study |
252 children and adolescents with migraine | Coenzyme Q10 (1–3 mg/kg daily) for average of three months | N/A | The headache frequency improved from 19.2 ± 9.8 days per month to 12.5 ± 10.8 days per month (p < 0.001). PedMIDAS score improved from 47.4 ± 50.6 to 22.8 ± 30.6 (p < 0.001) (grade improved from 2.6 ± 1.2 to 1.9 ± 1.0 (p < 0.001). Headache duration decreased from 11.7 ± 18.1 to 5.7 ± 9.1 h (p < 0.001). The 46% of patients achieving a 50% or greater reduction in headache frequency. | N/D |
| Slater et al., 2011 [30]: Crossover, add-on RCT |
120 children and adolescents with migraine | Coenzyme Q10 (100 mg daily) for four months (n = 60) | Placebo for four months (n = 60) | Significant reduction in headache frequency in both groups, but repeated measures ANOVA failed to show a time condition interaction (p > 0.05). No significant differences between both groups in migraine severity and duration. | N/D | |
| Magnesium | Wang et al., 2003 [31]: RCT |
118 children and adolescents with headaches suggestive of migraine | Magnesium oxide containing 9 mg/kg of elemental magnesium for four months (n = 58) | Placebo for four months (n = 60) | Both groups had a downward trend in headache days, with only the magnesium group sustaining the trend past six weeks; no significant difference between groups after regression analyses (p = 0.88) | Diarrhea or soft stools (n = 11) |
| Gallelli et al., 2014 [32]: Single-blind RCT |
160 children and adolescents with migraine | Magnesium (400 mg daily) and acetaminophen (15 mg/kg) or ibuprofen (10 mg/kg) to be taken with acute migraine episodes for 18 months (n = 40 and 40, respectively) | Acetaminophen (15 mg/kg) or ibuprofen (10 mg/kg) to be taken with acute migraine episodes for 18 months (n = 40 and 40, respectively) | Treatment with magnesium reduced pain intensity acutely when combined with acetaminophen or ibuprofen (p < 0.01) and resulted in a reduction of migraine frequency (p < 0.01) | None | |
| Melatonin | Gelfand et al., 2017 [33]: Small RCT (home-based trials using social media) |
31 children and adolescents with migraine | Melatonin 3 mg daily for three months (n = 18) | Placebo for three months (n = 13) | Mean migraine days was lower in the melatonin group vs the placebo group in the final 4 weeks of treatment (the primary outcome measure) but was not statistically significant.. | Daytime tiredness (n = 2), low iron on blood work (n = 1), and vomiting (n = 1) |
| Fallah et al., 2018 [34]: Parallel, single-blinded randomized clinical study |
80 children and adolescents with migraine | Melatonin (0.3 mg/kg, max 6 mg daily) for three months (n = 40) | Amitriptyline (1 mg/kg, max 50 mg daily) for three months (n = 40) | Significant reduction in headache frequency after treatment for three months was seen in 62.5%. The severity scores, duration, and PedMIDAS scores of the headaches reduced from 6.05 ± 1.63 to 4.03 ± 1.54, 2.06 ± 1.18 to 1.41 ± 0.41 h, and 33.13 ± 9.17 to 23.38 ± 9.51, respectively. But amitriptyline was significantly more effective in improving all of these indicators. | Excessive daytime sleepiness (n = 2) |
|
| Mirano et al., 2008 [35]: Prospective open-label trial study |
14 children and adolescents with migraine | Melatonin (3 mg/day daily) for three months | N/A | 10 patients reported that the headache attacks had decreased by more than 50% in respect to baseline. | Excessive daytime sleepiness (n = 1) |
|
| Fallah et al., 2015 [36]: Prospective open-label trial study |
38 children and adolescents with migraine | Melatonin (0.3 mg/kg daily) for three months | N/A | Monthly frequency, severity and duration of headache reduced from 15.63 ± 7.64 to 7.07 ± 4.42 attacks, from 6.20 ± 1.67 to 3.55 ± 2.11 scores, and from 2.26 ± 1.34 to 1.11 ± 0.55 h, respectively. | Sleepiness (n = 7): excessive daytime sleepiness (n = 3), vomiting (n = 4), mild hypotension (n = 2), and constipation (n = 1) | |
| Shahnawaz et al., 2019 [37]: Parallel, single-blinded randomized clinical study |
45 children with migraine | 0.3 mg/kg (maximum 6 mg) at bedtime |
Amitriptyline (1 mg/kg, maximum 50 mg) at bedtime (n = 45) | Significant better in amitriptyline group (p value < 0.05) in monthly frequency of headache, severity and duration, and headache disability PedMIDAS. | Side effects (35.6%), No serious adverse event. |
|
| Polyunsaturated fatty acids | Harel et al., 2002 [38]: Crossover RCT |
27 adolescents with migraine | Marine n-3 ethyl ester concentrate (two capsules daily) for two months (n = 14) | Placebo for two months (n = 13) | Significant reduction in headache frequency during Marine n-3 ethyl ester concentrate treatment and during placebo treatment but no significant difference between these treatments. | None |
| Fayyazi et al., 2016 [39]: Prospective open-labeled study |
25 children and adolescents with migraine | Omega-3 capsule (containing 1 g of fish oil) and valproate (20 mg/kg, max 200 mg) daily for two months (n = 12) | Placebo with valproate (20 mg/kg, max 200 mg daily) for two months (n = 13) | Significant reduction in headache frequency and PedMIDAS scores in case group and control group, but there were no statistically significant differences observed between the groups. |
Nausea (n = 1) | |
| Feverfew | Moscano et al., 2019 [40]: Observational multicenter study |
71 children and adolescents with migraine | Partena® tablets (Mg2+, CoQ10, VitB2, Feverfew, Parthenolides, Andrographis paniculate) daily for four months | N/A | In the assessment of both headache frequency and intensity, a significant effect of treatment and maintenance of it was found. | N/D |
| Vitamin D | Cayir et al., 2014 [41]: Prospective open-labeled study |
53 children and adolescents with migraine | Vitamin D supplementation (400 or 800 or 5000 IU) and Amitriptyline (1 mg/kg) daily for six months (n = 40) | Only amitriptyline (1 mg/kg daily) for six months (n = 13) | There was a significant decrease in migraine attacks in the groups receiving vitamin D compared with the group receiving amitriptyline alone. |
N/D |
| Fallah et al., 2020 [42]: In a single-blinded, randomized, clinical trial |
57 children and adolescents with migraine | 2 mg/kg/day of topiramate (n = 28) or 2 mg/kg/day of topiramate plus one 500,000 IU vitamin D3 pearl (n = 29) weekly for two consecutive months | N/A | The combination group of topiramate and vitamin D3 showed a significant effect on the reduction of monthly headache frequency (6.12 ± 1.26 vs. 9.87 ± 2.44, p = 0.01) and disability score (19.24 ± 6.32 vs. 22.11 ± 7.91, p = 0.02) compared with the topiramate alone group | Daily sleepiness (n = 2), constipation (n = 2), and anorexia (n = 1) | |
| Ginkgolide B | Usai et al., 2010 [43]: Prospective open-label study |
24 children and adolescents with migraine | Ginkgolide B, Coenzyme Q10, Vitamin B2, and Magnesium daily for three months | N/A | Starting with a mean baseline of 7.4 ± 5 attacks, clinical improvement was significant: the mean number of days of headache per month decreased to 2.2 ± 2.8 (p = 0.0015), with a decrease of number of analgesics used for the attacks from 5.9 ± 5.3 to 1.5 ± 2.2 (p = 0.013). | N/D |
| Esposito et al., 2011 [44]: Prospective open-label study |
119 children and adolescents with migraine | Ginkgolide B, Coenzyme Q10, Riboflavin, and Magnesium daily for three months | N/A | The mean frequency per month of migraine was significantly decreased (9.71 ± 4.33 vs. 4.53 ± 3.96 attacks; p < 0.001). | N/D | |
| Esposito et al., 2012 [45]: Prospective open-label study |
374 children and adolescents with migraine | Ginkgolide B, Coenzyme Q10, Riboflavin, and Magnesium daily for six months (n = 187) | L-tryptophan 5-hydroxytryptophan (from Griffonia simplicifolia), Vitamin PP, and Vitamin B6 daily for six months (n = 187) | Both preparations reduced all outcome measures, but reductions in headache frequency, duration and intensity, PedMIDAS score and behavioral reactions to headache were significantly greater in the ginkgolide B group. The ginkgolide B preparation was significantly more effective in the medium-term (six months). | None |
RCT: randomized controlled trial; MIDAS: Migraine Disability Assessment; N/A: not available. N/D: not described.