1. Migraine in children.
Similar to the principles for initiating prophylactic treatment in adults, prophylactic treatment may be considered if the frequency or severity of migraine in children is severely disruptive to life or leads to heavy use of acute phase medications.
(1) Non-pharmacologic treatment: Non-pharmacologic treatment is similar to that for adults, with relaxation, biofeedback, music therapy, and cognitive-behavioral therapy to cope with stress being equally appropriate for children. There is more evidence that these treatments may be more effective than beta-blockers.
Special attention is paid to the importance of sleep for the child. Children need 8 to 10 hours of sleep per day and a regular schedule, which can be relaxed on weekends, but must resume normal sleep requirements on Sunday night. Adolescents can sleep later on weekends, but it is better to wake up at the usual time and take a nap after eating properly to avoid irregular eating. It is recommended that the child maintain a regular routine, avoid stress and develop good sleep habits. About 1/3 of the affected children have exact trigger foods (e.g. chocolate, citrus, cheese, cured meats, yogurt, fried foods, monosodium glutamate, etc.), and caffeine intake should be avoided. Care should be taken to avoid dehydration during seizures.
(2) Medication: Calcium channel blockers: Only flunarizine has been shown to be effective in rigorously designed randomized double-blind controlled studies. All other drugs have insufficient evidence. In conclusion, there is an urgent need for well-designed trial evidence for migraine prophylaxis in children. The length of use of prophylaxis in children remains controversial, with some recommending use during the child’s semester and tapering off over the holidays, and others recommending short-term use (6 to 8 weeks).
Beta-blockers: There are three randomized double-blind controlled studies of ponerol with conflicting results, and all three have the disadvantage of small sample sizes. A double-blind crossover controlled study in adolescents aged 7 to 16 years showed that propranolol 60 to 120 mg/d (0.5 to 1 mg/kg/day in three divided doses) significantly reduced the frequency of headache attacks; however, another study using 80 to 120 mg/d did not find effectiveness and the mean headache duration in the propranolol group was instead longer than at baseline. Studies comparing propranolol with self-hypnotherapy also did not find that propranolol (3 mg/kg/day) helped prevent headache attacks. However, because of the positive findings, propranolol may be used as a second-line agent, usually at a starting dose of 1 to 2 mg/kg/d, with a slow increase to 3 mg/kg/d if tolerated, and usually with dose adjustments over 2 to 3 weeks. Another non-selective beta-blocker, timolol, did not show significant effectiveness in a randomized controlled study. No evidence for other selective beta-blockers, including atenolol, metoprolol, and nadolol.
Antiepileptic drugs: There is insufficient evidence for the use of antiepileptic drugs in children, mainly in retrospective studies. Topiramate had 3 retrospective studies showing effective results 256-258, but prospective randomized controlled studies of topiramate showed a trend toward effectiveness, but were not significant. There was evidence from 2 retrospective studies of valproic acid (minimum age 9 years) at a smaller therapeutic dose (10 mg/kg/d or 500 mg/day) than the antiepileptic one. Randomized, double-blind controlled studies comparing valproic acid and propranolol have shown comparable treatment effects for both. As in adults, the use of valproic acid requires attention to blood and liver function, and in female children, weight and ovarian function need to be considered. There are small sample retrospective studies evaluating the effects of levetiracetam (125-250 mg) and gabapentin (15 mg/kg), both of which showed effectiveness with few adverse effects.
Antidepressants: There is little evidence for the use of antidepressants in children or adolescents. Amitriptyline had two study results, one from an open subgroup analysis and the other from a retrospective study.266 Overall adverse effects were low. The starting dose of amitriptyline is 5 to 10 mg per night and may be slowly increased to 25 to 50 mg every 4 to 6 weeks. controlled studies of trazodone267 have not shown effectiveness. there is no trial evidence for SSRI. There is expert opinion that SSRIs may be an option for children with concomitant anxiety or depression, but caution is needed as the FDA has recently issued a warning about suicidal ideation in adolescents using these drugs.
NSAIDs: Naproxen has been shown to be effective in 1 small sample double-blind controlled crossover cohort study, with the main adverse effect being gastrointestinal reactions, so experts recommend limiting prophylaxis to 2 months.
Other medications: The root extract (Petadolex) did not show effectiveness in a randomized double-blind placebo-controlled study, although there were open studies suggesting effectiveness. Coenzyme Q10 has evidence from open studies only. Phenothiazine 1 mg/d did not show effectiveness in controlled studies. Cycloheximide has shown effectiveness in only 1 retrospective study and is more widely used abroad, with effective doses ranging from 2 to 4 mg/night three times daily. The main side effects are sedation and increased appetite.
2. Prophylactic treatment of menstrual migraine and menstrual-related migraine Menstrual migraine.
It includes short-term prophylaxis and continuous prophylaxis. The former is more acceptable to patients because it is administered only during the headache-prone period and is shorter in duration. Drugs with evidence of short-term prophylaxis include NSAIDs, tritans, magnesium, and hormone replacement therapy.
Naproxen sodium (550 mg twice daily) may reduce the level of pain in the acute phase, including headache in premenstrual syndrome.271 Studies have evaluated its specific effects in menstrual migraine; in one study, patients had less frequent and less severe headaches in the week before menstruation, but only a significant decrease in headache level compared with control. In the other 2 controlled studies, naproxen used for 1 week before and after the first day of menstruation reduced the frequency of headaches in the perimenstrual period, but failed to reduce headache severity in 1 study.
Tretinoin has also been used as short-term prophylaxis. Naratriptan (1 mg twice daily for 5 days starting 2 days before the expected menstrual period), frotratriptan (2.5 mg twice daily for 6 days during menstruation), and oral sumatriptan have been studied prospectively in small samples in controlled studies and shown to be more effective than control agents.
A small sample of controlled studies with magnesium salts showed positive results, with studies using magnesium pyroglutamate (Magnesium pyrrolidone carboxylic acid) 360 mg daily for the period from day 15 of the menstrual cycle to the end of that cycle, with a significant decrease in patient headache days.
Long-term prophylaxis may be considered if short-term prophylaxis is ineffective or inappropriate. However, there is no evidence from studies in this area. First-line prophylactic medications for migraine may be considered, or optionally, both long-term and short-term prophylactic therapy may be used.
Another type of prophylactic treatment is estrogen replacement therapy. The best evidence is that transdermal estradiol (gel or patch, at least 100 μg for 6 days during menstruation) is not as effective as beta-blockers or other first-line prophylactic agents. However, a recent study did not show effectiveness. Because hormone replacement therapy can increase the incidence of diseases such as ischemic heart disease and ischemic stroke, it is generally not recommended for patients with migraine with aura who are at significantly higher risk.
3. Migraine during pregnancy and lactation.
There are no specific clinical trials evaluating migraine treatment during pregnancy, and most migraine treatment medications are contraindicated. Fortunately, most migraineurs have fewer or no attacks during pregnancy. If prophylactic therapy has to be initiated during pregnancy, the patient and family must be informed of the risks and the extent of the benefits. For prophylactic treatment, only magnesium salts (300 mg/d for 2 days) and metoprolol are recommended for use during pregnancy (level B recommendation).
If the patient plans to become pregnant, a non-pharmacologic treatment is recommended.
During lactation, drugs that are not secreted through breast milk or secreted in very small amounts must be used. Valproic acid has been shown to be indicated in this setting. beta-blockers can be secreted via breast milk and may cause bradycardia in the infant.
4. Chronic migraine.
First, headache triggers must be controlled, including diet, sleep, exercise and psychological factors. Avoid foods and drugs that tend to aggravate headache, including caffeine, alcohol and tobacco. Evaluate the use of medications in the acute phase, and reduce the use of appropriate medications in patients with MOH.
The most well-documented medication is topiramate. Other prophylactic medications may also be chosen depending on the patient’s comorbidities and other specific circumstances. Botulinum toxin A may be effective in chronic migraine: a randomized double-blind controlled study using 100 units of botulinum toxin A was significantly more effective than placebo; positive results were also obtained in a pending multicenter randomized double-blind placebo-controlled study, PREEMPT. Randomized double-blind studies comparing botulinum toxin A with topiramate and valproic acid for the prevention of chronic migraine have all concluded that the effects are comparable and that botulinum toxin is better tolerated.
Combined behavioral and pharmacological treatment of comorbid psycho-affective disorders should be emphasized. 200 patients observed by Mathew et al. found combined treatment to be more effective than drug-only treatment (72-86% vs. 58%). In Grazzi’s study, migraine patients with medication-overuse headaches who received a combination of treatments had fewer headache days, medication use, and recurrence rates at 3 years compared to those treated with medication-only treatments. Overall, however, behavioral therapy was less effective in chronic headache patients without MOH than in those with episodic migraine (13% vs. 52% symptom relief). It was also less effective in patients with medication overdose headache than in those without MOH (29% vs. 52%). Occipital nerve stimulation (ONS) may be effective in preventing chronic migraine.