Approach

The emphasis in a treatment plan should be on reducing headache frequency, duration, severity, and associated disability, and treatment should be tailored to each child.[23] There are few controlled data to support the use of most of the drugs currently approved in the management of paediatric migraine. This has led to a tendency to extrapolate data from adult trials or to use anecdotal personal experience when considering any drug for use. The expectations for the success of treatment should take account of the level to which psychological factors are contributing to symptoms. Although the evidence to support the relevance of this is conflicting, there is a widely reasonable body of opinion that psychological factors play a significant part in influencing symptomatology perception and the success or failure of prescribed treatment.[24] Evidence to support this includes the significant placebo effect seen in much of the published data for specific pharmacological interventions.[25] Not all treatments work for every patient, and some patients will be non-responders, even to those medicines for which there is the clearest evidence available from controlled trials to support their use.

Management of acute episodes

The self-administration of simple analgesics, such as paracetamol and ibuprofen, in adequate doses, is a reasonable first approach to managing acute paroxysms.[26][27][28] [ Cochrane Clinical Answers logo ] Evidence of benefit from well-designed research studies is lacking, as high withdrawal rates (17%) and a failure to report results before crossover prevail in trials published to date. This may have introduced bias because of continued treatment effects after crossover and because of unequal withdrawals among groups. There is little evidence that paracetamol is more effective than ibuprofen, and both may induce analgesic headache with frequent use. Adverse effects with paracetamol are rare, although overdose may cause liver damage; ibuprofen may occasionally cause gastrointestinal upset and hypersensitivity reactions in a minority.

If simple analgesics prove ineffective, codeine is a potential next step (and last-resort option) used by some practitioners, although it is contraindicated in children younger than 12 years of age, and is not recommended in adolescents 12 to 18 years of age who are obese or have conditions such as obstructive sleep apnoea or severe lung disease as it may increase the risk of breathing problems.[29] It is generally recommended only for the treatment of acute moderate pain, which cannot be successfully managed with other analgesics, in children 12 years of age and older.[30][31] Strong evidence for benefit is lacking and the risk of adverse effects is high. Sedation and constipation are relatively common adverse effects, and respiratory depression occurs in overdose. It should be used at the lowest effective dose for the shortest period and treatment limited to 3 days.[30][31]

In children who experience paroxysms that include vomiting, an anti-emetic such as cyclizine, prochlorperazine, promethazine, or ondansetron may help to alleviate these symptoms and enhance the effectiveness of other oral therapies. The administration of these agents as early as possible in attacks is recommended.

For children with refractory symptoms, a 5-hydroxytryptamine 1 agonist such as intranasal sumatriptan may be considered. [ Cochrane Clinical Answers logo ] Published trials to date (although in small patient populations) seem to endorse the use of intranasal sumatriptan, and it is licensed for use in the UK in children 12 years of age and older.[27] It should be used as soon as possible in an attack. Adverse effects (disturbance of taste and smell) have been reported in around 20% of users. Few data support the use of oral sumatriptan, but it is licensed for use in the UK in children 6 years of age or older, and it may be used off-label in other areas.[13][32][33][34]

In addition to sumatriptan, the evidence base is slowly expanding to support the use of other drugs in the same class.[28] In one study, intranasal zolmitripan was found to be superior to placebo for providing some relief from migraine symptoms in adolescents, and was well tolerated. The most commonly reported side effects were taste disturbance, nasal discomfort, and nasal congestion, affecting approximately 20% of patients.[35] Oral rizatriptan is licensed for use in the US (in children 6 years of age and older) but not in the UK, although the evidence to unequivocally endorse use in the paediatric population is not yet available.[36][37][38] Oral almotriptan is licensed for use in adolescents (12 years of age and older) in the US but is not available in some other countries. The evidence for clinical benefit is from one double blind, placebo-controlled, parallel-group trial of patients aged 12 to 17 years.[39] The only other published paediatric data are limited to two small open label studies.[40][41] [ Cochrane Clinical Answers logo ]

For acute attacks, there is some trial evidence to support the use of a combination therapy that includes a triptan and a non-steroidal anti-inflammatory drug.[42][28]

Management of recurrent episodes

When the frequency and severity of migraine attacks interfere with school and social life, preventative drug treatment may be indicated, particularly if simple non-prescription analgesics prove ineffective in aborting attacks.[43] Counselling on lifestyle and behavioural factors that affect headache frequency, and assessment and management of comorbidities that may be associated with persistence of headache, should also form part of management.[44]

If prophylactic drug therapy is required, avoidance of polypharmacy is recommended. The use of each agent should be reviewed after an initial attempt at prophylaxis of around 3 months. If there has been no improvement in symptoms, the selected agent should be discontinued and an alternative considered. The use of long-term prophylaxis in children is best avoided if practical. Agents of apparent benefit to individual children should be periodically stopped (at least annually) and symptoms reviewed to evaluate whether prophylaxis is still merited.

Evidence to support the use of prophylactic agents is scarce. The majority of randomised controlled trials studying preventive medications for migraine in children and adolescents have not demonstrated superiority to placebo, and it remains unclear which agent offers the best prospect of a therapeutic response.[44] Agents that can be considered include propranolol, pizotifen, and topiramate. The evidence for benefit from propranolol from published studies is conflicting.[44] It should not be used in children with asthma. Athletes (who require adrenaline for performance) may be reluctant to use it. There is very little evidence available to support the routine use of pizotifen. Topiramate has been found to be beneficial in some studies; however, results vary depending upon outcome measures analysed.[45][44] Topiramate is approved in the US for the prevention of migraine headaches in adolescents aged 12 to 17 years.

The persistence of debilitating attacks may justify the use of other agents: amitriptyline, valproic acid, carbamazepine, and gabapentin are alternatives, although each requires initiation by a consultant and careful monitoring of adverse effects. Amitriptyline is preferred over anticonvulsant therapy, and in highly resistant cases verapamil and indometacin also merit consideration.[2] In 2018, the European Medicines Agency finalised a review of valproate and its analogues, recommending that these medicines are contraindicated for migraine prophylaxis during pregnancy due to the risk of congenital malformations and developmental problems in the infant/child.[46] In the US, valproate and its analogues are contraindicated for migraine prophylaxis in pregnant women. In both Europe and the US, valproate and its analogues must not be used in female patients of child-bearing age, unless there is a pregnancy prevention programme in place and certain conditions are met.[46]

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