Elsevier

Pediatric Neurology

Volume 29, Issue 5, November 2003, Pages 425-429
Pediatric Neurology

Review Article
Triptans for treatment of acute pediatric migraine: a systematic literature review

https://doi.org/10.1016/S0887-8994(03)00400-4Get rights and content

Abstract

The purpose of this article is to evaluate the effectiveness and safety of triptans for the treatment of acute migraine in children and adolescents. Randomized and open label trials of triptans in acute pediatric patients (ages 6-18 years) were identified by Medline (1966-2002) and PubMed (1991-2002). Additional reports were identified from the reference list of the retrieved studies. To study effectiveness, only randomized controlled trials were included, but open label studies were also included to study adverse effects. Pharmacokinetic studies of triptans in pediatric patients were also searched. Four randomized controlled trials were identified. One study reported oral sumatriptan, another oral rizatriptan, and two studies reported nasal spray sumatriptan. Rizatriptan is well tolerated but not clearly beneficial when used in adolescents. Effectiveness of nasal spray sumatriptan in acute pediatric migraine where other medications had failed was supported. Effectiveness of oral sumatriptan was not established. Adverse effects were minor for oral sumatriptan and rizatriptan and nasal sumatriptan. Pharmacokinetics of sumatriptan in pediatric patients has not been established. In conclusion, nasal spray sumatriptan should be considered in acute pediatric migraine in patients not experiencing adequate relief with other interventions.

Introduction

Headaches are a common complaint in children. In children, recurrent migraine is more common than recurrent tension-type headaches. The opposite is true of adults where chronic tension-type headaches are more than four times more prevalent than migraine [1].

Using the International Headache Society (IHS) 1988 criteria, recent studies indicate an overall migraine prevalence of 8.6% in American children ages 5-13 years [2] and 10.6% in 5-15 year-old Scottish children [3]. The prevalence of migraine increases considerably from childhood into adolescence [4] from 3.4% in 5-year-olds to a peak of 19.1% in 12-year-olds, dropping thereafter to 13.8% at age 15 years [3]. Sex distribution of childhood and adolescent migraine also differs with age. Before the age of 12, male and female distribution is nearly equal with a slight male preponderance [2], [5]. After the age of 12, however, females predominate, in a ratio of 2:1 [3].

A study of children aged 5-13 years, meeting the IHS criteria for migraine, revealed that 54.1% of children reported having an aura, of which 71% were visual. The headaches were described as pulsatile, and were aggravated by motion, noise, and bright light. During the migraine attack, 43% of the children had to stay in bed, and 27% were unable to attend school. Of these patients, their physicians had diagnosed only 19.8% as having migraine, and most of these had not received treatment [2].

The IHS migraine criteria are the current standard and have been demonstrated to be sensitive in adults. Migraine clinical presentation may be age-dependent, and pediatric modifications to the IHS criteria have been proposed. Childhood variances include more nonspecific constitutional symptoms and more difficult symptom verbalization. Proposed changes include changes in duration, location, and including photophobia or phonophobia [6].

A group of children and adolescents were examined to evaluate the proposed pediatric IHS criteria modifications [6]. Significant improvement in the diagnostic sensitivity occurred with the three modifications, from 66-93% in the sample as a whole, and from 49-87% in those under 12 years of age. No age dependency was observed in headache intensity or presence of nausea. These two criteria are the most relevant characteristics in the differential diagnosis of migraine [7]. It has been reported that migraine duration and occurrence of aura were more often fulfilled by adolescents, whereas the criteria of aggravation of headache by physical activity and photophobia were fulfilled mostly by children [7]. The number of episodes specified in the IHS criteria was fulfilled in almost all patients, demonstrating no age-associated differences.

One hundred juveniles (aged 3-17 years) suffering from chronic headaches (>90% migraine) were asked to complete a survey, draw their headache experience, and rank a list of choices concerning what they wanted to receive from a physician clinic visit [8]. The patients ranked three goals of treatment consistently highest. Seventy percent wanted to know the cause of the pain, 68% wanted pain relief, and 59% wanted reassurance that they did not have a brain tumor (even in ages 5 to 7). These results cannot be ignored when treating migraine in children.

In general, the migraine treatment in children as in adults can be preventive (prophylactic), symptomatic, or abortive. The goal of preventive therapy is to reduce either the frequency or intensity of attacks, or both. Pharmacologic migraine prophylaxis is considered if migraine attacks interfere with a child's normal routine and enjoyed daily activities owing to a frequency of more than 1 to 2 per week, or missing more than 3 days of school per month [9]. In an exploratory meta-analysis of behavioral and pharmacologic preventive therapies, biofeedback and muscle relaxation have been demonstrated to be promising in migraine prophylaxis [10]. If migraine attacks occur relatively infrequently or sporadically, the use of symptomatic medications is often the treatment of choice, especially in elementary school children with antiemetics and nonsteroidal anti-inflammatory drugs often the first-line agents [9].

Abortive migraine medications include ergotamines (historically) and, more recently, triptans. Sumatriptan is the triptan group's first-generation drug, with second- and third-generation naratriptan, zolmitriptan, rizatriptan, and almotriptan being available. Sumatriptan is available in several delivery systems, including subcutaneous, oral, rectal, and intranasal. Triptans have been demonstrated to be effective and safe in adult patients. On this basis, they are suggested for children and adolescents [9], [11], [12], albeit not U.S. Food and Drug Administration approved in patients less than 18 years of age. The purpose of this article was to evaluate the effectiveness and safety of triptans for the treatment of acute migraine in children and adolescents.

Section snippets

Methods

This study involved a systematic literature review. The following criteria were used to consider studies for this review:

  • Participants were aged 6-18 years, who suffered frequent migraine not responsive to other interventions.

  • Triptan medications, including sumatriptan, naratriptan, zolmitriptan, rizatriptan, and almotriptan administered subcutaneously, orally, rectally, or intranasally.

  • Outcome measures, including pain reduction, nausea control, photophobia resolution, and adverse effects.

To

Results

Efficacy of oral sumatriptan in 23 pediatric migraine patients was reported by Hämäläinen et al. [13]. Patients were to self-report pain on the Visual Analogue Scale before taking medication, 30 and 60 minutes thereafter, with the primary end point being a 50% decrease in pain intensity on a 100-mm scale at 2 hours. Secondary end points were preference, and pain intensity difference (single and summed). Most end points in the study appeared to favor sumatriptan over placebo, but only 22% of

Discussion

Inclusion criteria in all the randomized controlled trials reviewed here included fulfillment of the IHS criteria. Inclusion criteria for all but rizatriptan study [16] also included resistance to other commonly used antimigraine drugs. Revisions to the IHS criteria regarding duration have been proposed. One such revision is to decrease the duration of migraine attack to 1-48 hours, because young patients in general have shorter migraine episodes. Many of the end points of triptan studies use

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