Mirja L. Hämäläinen

Ibuprofen or acetaminophen for the acute treatment of migraine in children : A double-blind, randomized, placebo-controlled, crossover study

Efficacy of drugs for the acute treatment of migraine in children has not so far been studied in well controlled trials.We conducted a study to evaluate the efficacy of acetaminophen and ibuprofen. Eighty-eight children, aged 4.0 to 15.8 years, with migraine participated in a double-blind crossover study. Three attacks per child were treated in random order with single oral doses of 15 mg/kg acetaminophen, 10 mg/kg ibuprofen, and placebo at home. The primary end point, reduction in severe or moderate headache (grade >or=to 3 on a scale of 1 to 5) by at least two grades after 2 hours, was reached twice as often with acetaminophen and three times as often with ibuprofen as with placebo. Ibuprofen was twice as likely as acetaminophen to abort migraine within 2 hours. In the intent-to-treat analysis, children improved twice as often with ibuprofen and acetaminophen as with placebo. Both ibuprofen and acetaminophen are effective and economical treatments for severe or moderate migraine attacks in children. Ibuprofen gave the best relief. NEUROLOGY 1997;48: 103-107

Sumatriptan for migraine attacks in children: A randomized placebo‐controlled study Do children with migraine respond to oral sumatriptan differently from adults?

Oral sumatriptan is an effective acute treatment for migraine in adults, but its efficacy in children is still undetermined. Twenty-three children, aged 8.3 to 16.4 years, took both sumatriptan and placebo in a randomized, double-blind, placebo-controlled, crossover trial. The primary endpoint was a ≥50% decrease in pain intensity on a 100-mm visual analogue scale at 2 hours. Other endpoints of efficacy were pain intensity difference (PID), showing pain relief at each time point; summed pain intensity differences (SPIDs), estimating overall pain relief; and preference. Two hours after sumatriptan, 7 of 23 reached the primary endpoint, and after placebo, 5 of 23 (difference 9%, 95% CI for difference, −21 to 38%; p = ns). Within 2 hours, the headache disappeared completely in 5 of 23 children after sumatriptan and in 2 of 23 children after placebo (p = ns). Median PIDs were slightly better for sumatriptan between 0.5 and 4 hours (p = ns). Median SPIDs increased almost identically up to 2 hours. Thereafter, median SPIDs for placebo remained practically constant, whereas for sumatriptan, the improvement continued. At 4 hours, the median SPID for sumatriptan was 2.4 times as high as for placebo. However, the maximum differences between median SPIDs at 4 hours (38.5, 95% CI, −75.8 to 57.5; Wilcoxon signed rank test, p = 0.4) or at any other point were not statistically significant. Of the 23 children, 13 preferred sumatriptan and 2 placebo (sign test, p = 0.004). The failure of this and previous controlled studies suggests that the response of children to sumatriptan may be different from adults.

Nasal sumatriptan is effective in treatment of migraine attacks in children A randomized trial

Objective: To investigate the efficacy of nasal sumatriptan in migraine attacks of children and adolescents. Methods: A double-blind, placebo-controlled, two-way crossover trial was conducted in three hospital outpatient departments, with 8 to 17 year olds diagnosed with migraine serving as subjects (International Headache Society 1988). A single dose of sumatriptan nasal spray and a matching placebo were administered at home during two attacks. The sumatriptan dose was 10 mg for a body weight of 20 to 39 kg and 20 mg for those with a body weight of ≥40 kg. The primary efficacy endpoint was headache relief by two grades on a 5-grade face scale at 2 hours. Results: Eighty-three patients used both treatments and 11 only the first. At 2 hours, the primary endpoint was reached nearly twice as often after sumatriptan (n = 53/83; 64%) as after placebo (n = 32/83; 39%) (p = 0.003). Already at 1 hour, headache relief was seen more often after sumatriptan (n = 42/83; 51%) than after placebo (n = 24/83; 29%) (p = 0.014). The difference was even more obvious in patients who received the 20-mg dose as well as in the intention-to-treat analyses (n = 94). Other endpoints, including child’s preference and using rescue medication, also favored sumatriptan. The most common adverse effect was a bad taste after sumatriptan, reported in 29% (n = 26/90) of the attacks. No serious adverse effects were observed. Conclusion: Nasal sumatriptan is an effective and well-tolerated treatment for migraine attacks in children over 8 years of age.

A randomized trial of rizatriptan in migraine attacks in children.

Objective: To examine the efficacy of rizatriptan and the consistency of treatment response in migraine attacks of children and adolescents. Methods: We conducted a double-blind, placebo-controlled three-way crossover trial in patients ages 6 to 17 years diagnosed with migraine in two pediatric hospital outpatient clinics. Two doses of rizatriptan and a matching placebo were administered at home during three attacks. Rizatriptan dose was 5 mg for those with a body weight of 20 to 39 kg, and 10 mg for those with a body weight of 40 kg or more. The primary efficacy endpoint was headache relief by two grades on a five-grade face scale at 2 hours. Results: Ninety-six patients used all three treatments, 10 used two, and 10 only the first. At 2 hours, the primary endpoint was reached twice as often after both treatments of rizatriptan (first 74%, n = 71/96; second 73%, n = 70/96) as after placebo (36%, n = 35/96) (p < 0.001). Already at 1 hour, rizatriptan was clearly more effective as headache relief was reported by 50% (n = 48/96) and 55% (n = 53/96) of children after the first and the second dose of rizatriptan, compared to 29% (n = 28/96) after placebo (p = 0.004). Rizatriptan was superior at 3 and 4 hours, and the other endpoints also favored rizatriptan. Efficacy of rizatriptan was constant over the two treated attacks, and the findings were similar in children using the dose of 5 and 10 mg. No serious adverse effects were observed. Conclusions: Oral rizatriptan is effective and well-tolerated for migraine attacks in children over age 6 years.

Oral dihydroergotamine for therapy-resistant migraine attacks in children.

Twelve children with migraine symptoms that did not respond to conventional analgesics completed a double-blind, placebo-controlled, cross-over study of two doses of oral dihydroergotamine (DHE) for acute treatment. The primary endpoint was reduction of headache by > or = 2 grades on a 5-grade scale at 2 hours. After DHE, 7 of the 12 children reached the primary endpoint, and 2 reached the primary endpoint after placebo [difference 42%; 95% confidence interval (CI) 14%-70%]. Five of the 7 were pain-free after DHE (3 with 20 micrograms/kg; 2 with 40 micrograms/kg); none was pain-free after placebo. Headache recurred in 2 of the 5. Although headache recurrence limits the efficacy of oral DHE, it may be useful in the acute treatment of migraine in selected children.

Efficacy and tolerability of rizatriptan in pediatric migraineurs: Results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design

Background Treatment options for children and adolescents with migraine are limited. This study evaluated rizatriptan for the acute treatment of migraine in children and adolescents. Methods Randomized, double-blind, placebo-controlled, parallel-group trial in migraineurs 6–17 years old with unsatisfactory response to nonsteroidal anti-inflammatory drugs or acetaminophen/paracetamol. The trial included a double-blind run-in with weight-based rizatriptan dosing (5 mg for <40 kg, 10 mg for ≥40 kg). In the Stage 1 run-in, patients were randomized in a ratio of 20:1 placebo:rizatriptan and were instructed to treat within 30 minutes of a moderate/severe migraine. Patients with mild/no pain after 15 minutes of treatment (responders) took no further study medication, whereas patients with moderate/severe pain (non-responders) proceeded to take study medication in Stage 2. Non-responders who received placebo in Stage 1 were randomized 1:1 to rizatriptan:placebo, whereas non-responders who received rizatriptan in Stage 1 were allocated to placebo in Stage 2. The primary efficacy endpoint was pain freedom at 2 hours after Stage 2 dose in 12–17-year-olds. Results A higher proportion of 12–17-year-olds on rizatriptan had pain freedom at 2 hours compared with those on placebo: 87/284 (30.6%) versus 63/286 (22.0%), odds ratio = 1.55 [95% CI: 1.06 to 2.26], p = 0.025. Adverse events within 14 days of dose in 12–17-year-olds were similar for rizatriptan and placebo. The pattern of findings was similar in 6–17-year-olds. Conclusion Rizatriptan demonstrated a statistically significant improvement over placebo in eliminating pain and was generally well tolerated in migraineurs aged 12–17 and 6–17 years. Trial Registration ClinicalTrials.gov NCT01001234

Migraine attacks and sleep in children

Falling asleep as a means of ending migraine attack was studied in 133 4–16-year-old children in out-patient settings. Children registered 999 migraine attacks in headache diaries using a visual analogue scale (VAS) in 409 attacks and a five-face scale in 590 attacks. The distribution of maximal pain intensity was similar on both scales; on VAS 88% assigned grades between 63 and 100, and on the face scale 93% assigned grades of 4 or 5. Children fell asleep during 33% of the attacks (n = 329), in 64% of these within the first hour (n = 209). Of the children, 68% (n = 91) had fallen asleep at least once during an attack. Falling asleep was more common in children under 8 years of age than in older children. In those under 8 years, 62% (95% confidence interval (CI) 49–75%) of attacks were resolved by sleep, in those aged 8–12 years 34% (26–41%), and in children > 12 years 24% (15–33%) (anova, P < 0.0001). Pain was relieved without sleep in 43% (n = 431) of attacks, in 38% of these (n = 383) within the first 4 h. The data on migraine resolution were missing for 24% (n = 239) of the attacks, most often because the attack exceeded the 5-h observation period. This study confirms that migraine attacks in children are extremely painful and often resolve during an interval of sleep in children under 8 years of age.

Effect of age on the fulfilment of the IHS criteria for migraine in children at a headache clinic.

In a headache clinic, 247 children suffering from severe recurrent headaches were studied in relation to the IHS criteria for migraine. Of the 247, 163 had migrainous headache, with 110 (67.5%) of these having migraine in accordance with the IHS criteria. The remaining 53 (32.5%) had headache attacks fulfilling all but one of the IHS criteria. Coverage of the IHS criteria for migraine was 93%. Symptoms of unilateral headache, aggravation by physical activity, and nausea showed the greatest differences in frequency between those with migraine and those with probable migraine. All children with aura fulfilled criteria for migraine. Children with migraine with aura (11.8, 95% CI: 11.0–12.6 years) were older than those without aura (10.1, 9.4–10.8 years; p = 0.001). Children with pulsating headache were slightly older than children without pulsating headache. No differences in age were detected for the other IHS criteria.

Sleep alterations in juvenile neuronal ceroid-lipofuscinosis

In juvenile neuronal ceroid-lipofuscinosis (JNCL), sleep disorders are common. The purpose of this study was to investigate the sleep structure of 28 patients with JNCL compared with healthy controls subjects and to clarify the pathophysiology underlying the sleep disturbances in these patients. Each of 28 patients with JNCL (age range = 6-27 years), with or without sleep complaints, underwent one night of polysomnography. Electroencephalographic, electro-oculographic, electromyographic, and electrocardiographic findings were recorded. Sleep was scored and analyzed visually. The sleep parameters of the patients were compared with those of healthy control subjects. In most of the patients, the total sleep time, sleep efficiency, and percentages of rapid eye movement (REM) and non-REM (NREM) stage 2 sleep were significantly decreased, and the percentages of NREM stage 1 and slow-wave sleep and the number of nocturnal awakenings significantly increased. The percentage of NREM stage 1 and the number of awakenings increased with age and clinical stage. Paroxysmal epileptiform activity during light sleep (NREM stages 1-2) and high-amplitude delta-wave activity with intermingled sharp waves during slow-wave sleep were characteristic of the recordings. The present study revealed that in patients with JNCL, sleep is consistently altered.

Pain and disability in migraine or other recurrent headaches as reported by children

To evaluate the pain intensity and physical disability during migraine attacks, 340 children suffering from headache were studied in an outpatient setting. A validated self‐reporting five‐faces scale was used. Intensity of headache was more severe and attacks longer but less frequent in 253 children with migraine than in 87 children with other types of headache. On a pain scale, 69% of the children with migraine expressed maximal pain vs 32% of those with other types of headache. Bed rest for migraine attacks was required by 96% of the children. Severe migraine was at least as common in prepubertal as in pubertal children. The severity of the pain and disability related to migraine attacks should be evaluated carefully and treated appropriately.