Treatment of Pediatric Migraine

The treatment of children with migraines can be complex but particularly rewarding when successful. In this article, we will discuss drug therapy (tricyclics, beta blockers and antihistamines) as well as non-medical interventions in the pursuit of effective treatment.

Prophylactic drug therapy must be considered in children and adolescents whose headaches remain frequent, severe, or otherwise troublesome despite other interventions. These other interventions may include non-medicinal approaches or the use of abortive medications. Some non-medicinal approaches are aimed at the elimination or amelioration of triggers such as ingested substances, inadequately corrected vision, dental, sinus, or other sources of chronic pain. Dietary interventions (eliminating caffeine, milk products, MSG, gluten, preservatives, etc., not to mention assuring a regular schedule of nutritious meals) are occasionally helpful. Reassurance that there is not underlying condition such as brain tumor may greatly ameliorate headache complaints.

Non-Medical Interventions
Visual and dental problems and treatment of allergies and other sources of nasal congestion may prove beneficial, but it must be remembered that most individuals who experience troublesome headaches on the basis of problems of these sorts are actually migrainic and may still experience headaches despite such interventions. Environmental manipulations may help, especially in instances where chronic and repetitive activities result in muscular strain of head, neck, or shoulders. Aromas, light, sound, motion, and other important headache triggers for migraineurs that
can be eliminated in some cases-important examples including journeys to school on windy roads in poorly ventilated, carbon monoxide-spewing buses, "sick buildings," tobacco smoke, and so forth.

Non-medical approaches may be aimed at the more common sources of headache exacerbation, such as poor sleep, stress, anxiety, and depression. A thorough evaluation yielding the authoritative conclusion that a given child or adolescent has migrainous headache may go a long way toward alleviation of anxiety. Troublesome headaches lead parents and child to consider the possibility of brain tumor or serious vascular disease, a suspicion often enough reinforced by a history of brain tumor in a grandparent or a ruptured aneurysm in a distant cousin. It is sometimes unclear whether a prophylactic medication, offered and accepted on the first visit, provides pharmacodynamic benefits or just happens to be taken by someone whose chronic anxiety about a serious etiology for headache has been relieved. In some instances a normal brain image scan is necessary in order to achieve this sort of relief from worry.

Relaxation, massage and regular physical exercise may prove helpful once it is ascertained-as is very often the case-that sleep, stress, anxiety and depression play a roles in headache frequency and severity. Recognition that such factors are at work also figures importantly in the selection of prophylactic medications and often enough the use of medication provides an easier solution for family, child, and physician than selection and practice of an appropriate program of changes in "lifestyle" or personality. Other possible indications for prophylactic treatment are listed in Table 1.

Table 1
Prophylactic Treatment Indicators

1. Overly frequent use of abortive medications (risk for rebound headache)
2. Infrequent headaches that are severe, debilitating (e.g. cyclic vomiting), or potentially injurious to brain (e.g. hemiplegic or ophthalmoplegic migraine)
3. Severe headaches that achieve peak intensity too quickly to permit even rapidly acting abortive agents to work.

Medications
In many cases the headaches listed in this table are poorly responsive to abortive agents. In addition to consideration of triggers and characteristics of headache, other syndromic features may be of importance in the selection of prophylactic agents. The age and capacity of the child for ingestion and the presence of medical contraindications for the use of a particular drug must be considered in selecting a prophylactic agent. Selection must be made upon the basis of an extensive but informally accumulated experience in treating these disorders. There is almost no information derived from carefully designed scientific trials upon which to rely.

In this discussion, familiarity with the pharmacokinetic and pharmacodynamic properties of medications discussed is an essential prerequisite for utilization of these drugs. So is good judgment. It must be understood that recommendations provided here are generalities and that in the space provided very specific contraindications to the use of various drugs may not be noted or considered in detail. Nor is every possible side effect considered in this brief review.

For "garden variety" common or classic migrainous headaches occurring in children, the mainstays of prophylactic therapy are amitriptylene, nadolol, or propranolol. They are used because they are generally safe and effective, and because they are available in forms that most children can swallow. A third prophylactic agent that is widely employed is the antihistaminic cyproheptadine. These three drugs will be considered in this column. Space does not permit a consideration here of other important prophylactic agents, including calcium channel blockers, SSRI's and anticonvulsants.

Amitriptylene
The sedative effects of amitriptylene likely prove an asset in the management of migraine, and are particularly attractive in the treatment of the common combination of migraine and disturbed sleep. The antidepressant effects of this medication are also helpful in patients who have both migraine and depression. It is important, in electing to use this drug in children, that its antidepressant effects be mentioned. The family should be told whether the choice is or is not based upon detection of depression in the child. Pharmacist's comments (e.g. "So is your six year old depressed, Mrs. Jones?") may otherwise provoke confusion, misunderstanding and poor acceptance of the drug.

Amitriptylene is of greatest benefit when given at or near bedtime, 9-12 hours before one is likely to get up in the morning. Unacceptable sedative effects may be encountered in patients of any age, especially when the initial dose is too high. Girls and women may be more sensitive to these effects and it is our practice to start with very small doses (5-10 mg doses if weight is greater than 35 kg) with gradual upwards titration as needed, seldom administering more than 25 mg total evening dose. Boys weighing more than 35 kg may tolerate a starting evening dose of 12.5 mg, titrating upwards as needed, but seldom requiring or tolerating evening doses greater than 50 mg. There are no clear guidelines for treatment of children under five. Do not exceed doses of 2mg/kg/day in individuals weighing less than 35kg. In those uncommon instances that we choose to use these drugs in such small children (none less than four years old) we never exceed total daily doses of 10 mg.

Very little is known about the benefits and risks of amitriptylene in children less than five years of age, although the drug has been used with safety and apparent success in very young migraineurs. Nor is it known whether these small doses pose a definite risk for cardiac toxicity in children when used at these very small doses. It is unclear whether an EKG should be obtained in the otherwise normal child before providing amitriptylene, or whether a normal EKG should provide assurance that no untoward consequences will result from treatment at these low doses. Cardiac toxicity is likely extremely rare in normal children older than five, but as in so many other areas of the pharmacology of children, there remains a degree of uncertainty about the safety of this medication, despite the fact that it is widely prescribed.

We use this drug very commonly in children over five years of age, in the doses noted above and do not obtain an EKG unless there is some clinical indication. Other potential side effects include constipation, dry mouth, and urinary hesitation, complaints seldom voiced by children we have treated, and only very occasionally noted by adolescents. Modest weight gain occurs in some individuals, particularly adolescents, treated with amitriptylene prophylaxis.

Nortiptylene
Another tricyclic, nortiptylene, has proven useful in prevention of migraine and may be less sedative, but is considerably more expensive and has had a more worrisome association with risk for cardiac arrhythmia. In individuals weighing more than 40kg and older than 10 years of age we start with 10 mg doses administered at bedtime and never use more than 50 mg for treatment of migraine. In those instances where nortriptylene prophylaxis is selected, we routinely obtain an EKG-not because we regard a normal EKG as reassuring regarding the rare late occurrence of cardiac arrhythmia, but in order that a pre-existing abnormality such as first degree heart block be detected prior to treatment rather than later when the finding might be inappropriately blamed on nortriptylene.

Other Tricyclics
Doxepin is another tricyclic that some patients find less sedative than amitriptylene. Bedtime dosage is similar to amitriptylene, starting low and increasing as needed and as tolerated, the total safe and well-tolerated dose seldom exceeding those described for amitriptylene. Imipramine is another tricyclic that is occasionally helpful as a migraine prophylactic agent, particularly in the setting of the combination of migraine and nocturnal enuresis. Initial doses range from 5-25 mg at bedtime and for the treatment of migraine we never exceed 50 mg total daily doses. No patient should receive more than 2.5 mg/kg/day.

Contraindications & Side Effects
Tricyclics should not be administered to children or adolescents with cardiac disease unless absolutely necessary and with the approval and close supervision of a pediatric cardiologist given the possible risks of sinus tachycardia and prolongation of conduction time. Tricyclics should never be administered to patients receiving monoamine oxidase inhibiting medications since convulsions, hyperpyretic crisis, and fatalities have occurred in patients receiving both types of medication.

Many of the beta adrenergic blocking drugs developed for the treatment of blood pressure are effective migraine prophylactic agents. In practice, it is best to become intimately familiar with the benefits, contraindications, and side effects of a few. All share the same spectrum of possible side effects, particularly including sedation, lassitude, postural hypotension, vivid dreams, and loss of the usual degree of emotional spontaneity.

The last of these is the effect we most commonly encounter. It appears to represent a "mellowing out" of the child or adolescent, an effect that may have beneficial effects on stress-related migraine. On the other hand the parent does not always welcome the change from the child whose personality is represented in the nickname "Sparkie" to something superficially resembling that of a sixties beat poet. The change is usually much milder, however, and these medicines are often very well tolerated and very effective. We believe that there is little potential for these medicines to provoke depression in children at the doses we employ although the changes just noted may incorrectly suggest depression.

There are many other potential side effects of these medications with which a prescribing physician must be familiar, and these medications have no place in treatment of migraine in individuals who have diabetes and only a very limited role in the treatment of patients with asthma. Use in asthmatic patients should be limited to those with very mild asthma in whom other prophylactic choices have proven ineffective or were poorly tolerated, and such use should be subjected to careful follow-up scrutiny. They are also contraindicated in individuals with cardiac failure, or greater than first degree heart block.

Beta Blockers
Beta blockers may be especially beneficial in the treatment of individuals with migraine and hypertension, although in such instances the etiology of the hypertension and other potentially compromising circumstances must be carefully considered. Although it would seem prudent not to use beta blockers in patients who have had syncopal episodes, we have had considerable success in the use of these agents in otherwise normal individuals who have the frequently encountered combination of migraine and occasional syncope.

We have had similar success in patients with migrainous vertigo or dizziness suggestive of "posterior circulation migraine." It is obvious that these drugs should be discontinued if they result in worsening of such symptoms in the otherwise normal individual and that they should be used with great care if there are any pertinent associated medical conditions. In such instances prior consultation with other specialists may be required.

Generally, we have observed that long-acting beta adrenergic blocking preparations are better tolerated by children and adolescents than short acting preparations. Total daily doses of propranolol should start at approximately 1 mg/kg/day, divided into two doses each day for short acting preparations. This can be titrated upwards to doses as high as 4 mg/kg/day for individuals weighing 40kg or less. Where possible, we have found it valuable to initiate 60 mg or 80 mg "long acting" capsules of propranolol in individuals weighing more than 40 kg or those whose total daily dose of short acting preparation is 60 mg or 80 mg, respectively. Large adolescent patients may tolerate and benefit from the administration of even higher doses. The 80 mg long-acting dose has been difficult to obtain recently.

Nadolol is a valuable alternative that we have used more and more frequently as an initial therapy for migraine, since it appears in many instances to be less sedative and better tolerated than propranolol. We have tended to start with single morning doses of 20 mg in children weighing 30-40 kg, 40 mg in children weighing more than 40 kg, and increasing the dosage as needed and tolerated to total daily doses as high as 160 mg. Doses higher than 40 mg may have to be divided into twice-daily regimens, depending upon the size of the patient and tolerance.

In some instances it may appear prudent to avoid beta adrenergic blocking drugs in individuals who participate in sports. This decision must be individualized. The chief consideration in most instances will involve the questions of negative effects on cardiac and cardiovascular responses to physical activity and the question of the possible effects of these agents on performance. In considering these questions, it must be recalled that some professional athletes with particular cardiac problems are only able to participate due to the use of these forms of medication and that despite that may achieve very high levels of performance. For the usual situation, such as the participation of the ten year old in community soccer programs, these drugs have little detectable effects on cardiovascular or personal performance.

Child or adolescent musicians and public speakers with migraine may benefit from the effects that these medications have on tremor or performance anxiety. These drugs prove useful in the not infrequent combination of migraine and anxiety, or the less frequent combination-observed chiefly in boys-of migraine and rage. Adolescent male sexual function while using prophylactic beta-adrenergic blocking agents is a complicated topic that may require tactful consideration. We have found these agents beneficial in treatment of the combination of migraine, behavioral problems, and sexually inappropriate behavior in individuals with mental retardation.

Antihistamines
Cyproheptadine, the last of the older migraine prophylactic agents to be considered, is of particular value in the treatment of cyclic vomiting and of migraine in which vomiting is particularly prominent. It is safe and well tolerated in very young children. Total daily doses of approximately 0.25 mg/kg/day are usually employed and for small children there is the convenience of a liquid preparation. The sedative qualities of this medication should not be underestimated. Many parents refuse to continue this medication after administering doses that are weight appropriate but too high at the outset. We start with a small bedtime dose, adding morning and midday doses gradually, and seldom exceeding a total daily dose of 12 mg in any child. Only much smaller maximal daily doses are tolerated by very small children.

Cyproheptadine is useful in various forms of migraine other than migrainous cyclic vomiting, but the use of this agent is limited on older children and especially in adolescents not only by sedation, but by the very striking increase in appetite and ensuing weight gain that complicates the life of so many children. This effect makes this drug an attractive agent for treatment of migraine in some scrawny 5-10 year old boys, and a very poor idea for the treatment of adolescent girls or boys. Occasionally, this agent achieves the dual purpose of treating migraine and environmental allergies. Other aspects of the side effects and contraindications to the use of this generally safe agent should be reviewed prior to use.

Robert S. Rust, MD, rsr6f@virginia.edu

This article was first published in the Practical Neurology.