Introduction
Management of headaches
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Establish the diagnosis.
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Ask for triggers and assess degree of disability.
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Educate the child and family about the condition.
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Use a headache calendar to establish the characteristics of headache and associated symptoms.
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Establish realistic expectations and set appropriate goals.
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Discuss the expected benefits of pharmacological and non-pharmacological therapy and the time course to achieve them.
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Reduce the emotional mechanisms (on a personal level, within the family and at school) that provoke stress and may favour headache attacks.
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Advise to maintain a sound rhythm in daily life, which includes regular meals, sufficient fluid intake, physical exercise and sleep.
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Advise how to cope with trigger factors.
Non-pharmacological treatments
Non-pharmacological treatment of migraine
Non-pharmacological treatment of TTH
Pharmacological treatments
Pharmacological treatment of migraine
Symptomatic drug treatment
References | Drug | Study design | Evidence level | Dose | Age (years) | Number of patients | Responders (%) | p value | |
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Active drug | Placebo | ||||||||
Hamalainen et al. [31] | Ibuprofen | RCT | A | 10 mg/kg | 4–16 | 88 | 68 | 37 | <0.05 |
Lewis et al. [32] | Ibuprofen | RCT | 7.5 mg/kg | 6–12 | 84 | 76 | 53 | 0.006 | |
Evers et al. [33] | Ibuprofen | RCT | 200–400 mg | 6–18 | 32 | 69 | 28 | <0.05 | |
Hamalainen [31] | Acetaminophen | RCT | B | 15 mg/kg | 4–16 | 88 | 54 | 37 | <0.05 |
Hamalainen et al. [34] | Dihydroergotamine | RCT | C | 20, 40 μg/kg | 5–15 | 12 | 58 | 16 | NS |
Ueberall [35] | Sumatriptan nasal | RCT | A | 20 mg | 6–10 | 14 | 86 | 43 | 0.03 |
Winner et al. [36] | Sumatriptan nasal | RCT | 5–10–20 mg | 12–17 | 510 | 66a | 53 | <0.05 | |
Ahonen et al. [37] | Sumatriptan nasal | RCT | 10–20 mg | 8–17 | 83 | 64 | 39 | 0.003 | |
Winner et al. [38] | Sumatriptan nasal | RCT | 20 mg | 12–17 | 738 | 61 | 52 | NS | |
Hamalainen et al. [39] | Sumatriptan oral | RCT | C | 50–100 mg | 8–16 | 23 | 30 | 22 | NS |
Mac Donald [40] | Sumatriptan sc. | OT | C | 3–6 mg | 6–16 | 17 | 64 | – | – |
Linder [41] | Sumatriptan sc. | OT | 0.06 mg/kg | 6–18 | 50 | 78 | – | – | |
Winner et al. [42] | Rizatriptan | RCT | C | 5 mg | 12–17 | 196 | 66 | 56 | NS |
Visser et al. [43] | Rizatriptan | RCT | 5 mg | 12–17 | 234 | 68 | 69 | NS | |
Visser et al. [43] | Rizatriptan | OT | 5 mg | 12–17 | 686 | 77 | – | – | |
Linder and Dowson [44] | Zolmitriptan oral | OT | C | 2.5–5 mg | 12–17 | 38 | 88–70 | – | – |
Evers et al. [33] | Zolmitriptan oral | RCT | 2.5 mg | 6–18 | 32 | 62 | 28 | <0.05 | |
Charles [45] | Almotriptan oral | OT | B | 6.25–12.5 mg | 11–17 | 15 | 86 | – | – |
Linder et al. [46] | Almotriptan oral | RCT | 6.25–12.5–25 mg | 12–17 | 866 | 67–73 | 55 | <0.001 |
Outcome | ||||
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Pain relief | Pain-free | Recurrence | Need for rescue medications | |
Oral medication | ||||
Acetaminophen (n = 1) | + | − | − | − |
DHE (n = 1) | − | − | − | − |
Ibuprofen (n = 3) | + | ± | − | ± |
Rizatriptan (n = 3) | ± | − | − | ± |
Sumatriptan (n = 1) | − | ± | − | − |
Zolmitriptan (n = 2) | ± | ± | − | + |
Intranasal medication | ||||
Sumatriptan (n = 4) | ± | ± | − | ± |
Intravenous medications | ||||
Prochlorperazine (n = 1) | + | ? | − | ? |
Ketorolac (n = 1)* | ? | ? | ? | ? ± |
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At 1 h acetaminophen tended to be slightly more effective (39% of children relieved) than ibuprofen (37% of children relieved), but 2 h after administration ibuprofen was more effective (68 vs. 54%).
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Sumatriptan nasal spray was superior to placebo and was well tolerated. No serious adverse events occurred with taste disturbance as the most common one.
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Pain relief at 2 h was achieved in significantly more attacks treated with rizatriptan 5-mg tablets (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%).
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Pain relief rates after 2 h were 28% for placebo, 62% for zolmitriptan and 69% for ibuprofen (placebo vs. zolmitriptan p < 0.05; placebo vs. ibuprofen p < 0.05). Both drugs are well tolerated with only mild side effects.
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The Food Drug Administration has recently approved almotriptan for the acute treatment of migraine headache in adolescents. Nevertheless, almotriptan is still not approved in Europe.
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There are limited data about other triptans.
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In summary, there is moderate evidence that analgesics (acetaminophen and ibuprofen) and nasal-spray sumatriptan are more effective than placebo treatment. Based on the available literature, no differences in effect were found between the different compounds.
Prophylactic drug treatment
References | Drug | Daily dose | Age in (years) | Number of patients | Study design | Evidence level | % responders or p values (*) |
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Antihypertensive drugs | |||||||
Ludvigsson [50] | Propranolol | 60–120 mg | 7–16 | 28 | RCT | C | 82 vs. 14% |
Forsythe et al. [51] | Propranolol | 80 mg | 9–15 | 39 | RCT | NS | |
Olness et al. [52] | Propranolol | 3 mg/kg | 6–12 | 28 | RCT | NS | |
Sillampää [53] | Clonidine | 25–50 μg | ≤15 | 57 | RCT | C | NS |
Sills et al. [54] | Clonidine | 0.07–0.1 mg | 7–14 | 43 | RCT | NS | |
Calcium channel blockers | |||||||
Guidetti et al. [55] | Flunarizine | 5 mg | 10–13 | 12 | OT | A | 66% |
Sorge et al. [56] | Flunarizine | 5 mg | 5–11 | 63 | RCT | p < 0.001 (HA frequency) p < 0.01 (HA duration) | |
Visudtibhan et al. [57] | Flunarizine | 5–10 mg | 7–15 | 21 | OT | %66 | |
Battistella et al. [58] | Nimodipine | 10–20 mg | 7–18 | 37 | RCT | C | NS |
Serotonergic drugs | |||||||
Gillies et al. [59] | Pizotifen | 1–1.5 mg | 7–14 | 47 | RCT | C | NS |
Lewis et al. [60] | Cyproheptadine | 2–8 mg | 3–12 | 30 | OT | C | 83% |
Antidepressants | |||||||
Battistella et al. [61] | Trazodone | 1 mg/kg | 7–18 | 35 | RCT | C | NS |
Hershey et al. [62] | Amitriptyline | 1 mg/kg | 9–15 | 192 | OT | C | 80% |
Lewis et al. [60] | Amitriptyline | 10 mg | 3–12 | 73 | OT | 89% | |
Anticonvulsants | |||||||
Caruso et al. [63] | Divalproex sodium | 15–45 mg/kg | 7–16 | 42 | OT | B | 76% |
Sedaroglu et al. [64] | Divalproex sodium | 500–1,000 mg | 9–17 | 10 | OT | p = 0.000 (HA severity) p = 0.002 (HA frequency) p = 0.001 (HAduration) | |
Hershey et al. [65] | Topiramate | 1.4 ± 0.7 mg/kg | 8–15 | 75 | OT | A | p < 0.001 (HA frequency) |
Winner et al. [66] | Topiramate | 2–3 mg/kg | 6–15 | 162 | RCT | NS | |
Lewis et al. [67] | Topiramate | 100 mg | 12–17 | 103 | RCT | 72% | |
Miller [68] | Levetiracetam | 250–1,500 mg | 3–17 | 19 | OT | B | p < 0.0001 (HA frequency) |
Pekalnis et al. [69] | Levetiracetam | 250–1,500 mg | 6–17 | 20 | OT | p < 0.0001 (HA frequency) | |
Belman et al. [70] | Gabapentin | 15 mg/kg | 6–17 | 18 | OT | C | 80% |
Pakalnis and Kring [71] | Zonisamide | 5.8 mg/kg | 10–17 | 12 | OT | C | 66% |
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Flunarizine is an effective drug. Its use is limited by daytime sedation found in 10% of the patients and weight gain in more than 20%. Because of probable D2 receptor interaction it should not be given for more than 3 months (administering it in the early evening can avert daytime sleepiness, dosage 5 mg/die) [72, 73].
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Propranolol was found to be superior to placebo in one randomized controlled trial and not effective in two others. It was found to activate asthma in subjects with atopic disorders or a positive history of atopic disorders, and there are no follow-up studies concerning long-term risks of betablockers. Therefore, some centres do not use betablockers for migraine prophylaxis in children.
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The overall positive response rate of cyproheptadine was 83% and common side effects included sedation and increased appetite.
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There are limited confirmative data about trazodone.
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Amitriptyline (1 mg/kg) is an effective drug with an 84.2–89% positive response rate and only mild sedation was reported as side effect.
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Divalproex sodium (15–45 mg/kg/day) is an effective drug with 50% headache reduction seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9.5% of patients became headache-free after 4 months of treatment. The observed side effects were dizziness, drowsiness and increase in appetite.
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Topiramate is an effective drug for the reduction of headache frequency, severity and duration. The most common side effects reported were cognitive (12.5%), weight loss (5.6%) and sensory (2.8%).
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There are limited data about levetiracetam, gabapentin and zonisamide.
Pharmacological treatment of TTH
Treatment of cluster headache
Life quality of headaches
Conclusions
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Management of migraine and TTH should include strategies relating to daily living activities, family relationships, school, friends and leisure time activities.
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Management should be completed by education (both of the children and parents), non-pharmacological interventions and psychosocial support.
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With reference to symptomatic treatment, the drug should be taken as early as possible and in the appropriate dosage. In cases with early onset of nausea and/or vomiting endorectal or parenteral administration should be preferred. Antiemetic drugs should not be provided if the child vomits only once or headache stops after vomiting. If an antiemetic is required, ondansetron may be preferred for its good tolerability. Supplementary measures such as rest in a quiet, darkened room is recommended.
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Multidisciplinary treatment is an effective strategy for children and adolescents with improvement of multiple outcome variants including frequency and severity of headache and school days missed because of headache.
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In the pharmacological treatment age and gender of children, headache diagnosis, comorbidities, need and side effects of medication must be considered.
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As a growing problem both children and families should be informed about medication overuse and the children’s drug-taking should be checked.
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Regular follow-up care is needed, especially for those children with more severe initial headache presentation.