A placebo-controlled crossover trial of nimodipine in pediatric migraine. A placebo-controlled crossover trial using trazodone in pediatric migraine. Flunarizine v. placebo in childhood migraine. A double-blind study. [Flunarizine and dihydroergotamine in the treatment of migraine in children]. [The treatment of juvenile migraine using flunarizine or propranolol]. Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled, crossover study. Clonidine prophylaxis of childhood migraine and other vascular headache. A double blind study of 57 children;. Pizotifen (Sanomigran) in childhood migraine. A double-blind controlled trial. Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine. Propanolol ('Inderal') in the treatment of childhood migraine. Clonidine and childhood migraine: a pilot and double-blind study. Propranolol used in prophylaxis of migraine in children. L-5-hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. [Prevention of migraine with flunarizine and acetylsalicylic acid. A double-blind study]. [Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo)]. Papaverine in the prophylaxis of migraine and other vascular headache in children.
An 8-month, double-blind, placebo-controlled crossover trial was carried out on the use of nimodipine in migraine prophylaxis in 37 patients aged 7 to 18 years old. After a 4-week medication-free run-in period, 19 subjects (Group 1) received a placebo while 18 (Group 2) received nimodipine (10-20 mg t.i.d., according to body weight), for 12 weeks. After a 4-week wash-out period, the groups switched therapy for a further 12 weeks. 30 patients completed the trial and the number of dropouts was comparable in the 2 groups. The only side-effect during nimodipine treatment was mild abdominal discomfort (3 cases). The treatments were evaluated on the basis of frequency and duration of attacks. There was a significant reduction in both parameters during the first period of treatment. During the second period of treatment, nimodipine proved to have a significantly greater effect than the placebo with regard to frequency, whereas the response was similar with the placebo as regards duration of attacks. The latter parameter shows a significant decrease during the treatment periods, regardless of type of therapy. An 8-month, double-blind, placebo-controlled cross-over trial was carried out on the use of trazodone in pediatric migraine prophylaxis. It involved 40 patients aged 7 to 18 years old and suffering from migraine without aura, randomly divided into 2 groups. After a 4-week run-in period, Group A received oral trazodone (1 mg/kg a day divided into 3 doses) for 12 weeks, while Group B received a placebo. After a further 4-week washout period, Group A was given the placebo and Group B was treated with trazodone for a further 12 weeks. The trial was completed by 35 patients, the number of drop-outs being comparable in the two groups. During the first treatment period, both the frequency and the duration of the migraine episodes were significantly reduced in both groups. During the second, a significant further improvement in both parameters was only observed in Group B. No side-effects were observed at any time. Our results showed that, like other antidepressants, trazodone is a valid prophylactic agent for juvenile migraine. Successful migraine prophylaxis with flunarizine has been reported in adults by several authors. We used flunarizine in a double-blind, placebo controlled, randomized trial in childhood migraine. Twenty-four children with classical or common migraine were followed by a 12-week flunarizine treatment period. Each patient took 5 mg/day of the drug before going to sleep. Twenty-four children with similar clinical characteristics were assigned to placebo treatment. Efficacy of flunarizine versus placebo was assessed on the basis of the reduction of headache frequency and duration. A statistical comparison was performed between values reported in the treatment period and those in the three months before. Children treated with flunarizine experienced a statistically significant reduction in headache (66%) and duration (51%). These results were statistically superior to those observed in the placebo group. Sixteen patients on flunarizine therapy experienced an improvement of more than 50% of both parameters. We found flunarizine is an effective agent in children's migraine prophylaxis. Moreover it is suitable for the low incidence of mild side effects. We administer during 6 months in randomised way dihydroergotamine or flunarizine to 50 children affects of classical or common migraine. A significative improvement was estimated in frequency, intensity and duration of their crisis in 87% with dihydroergotamine and 79% with flunarizine, without significative differences from one to other. Dihydroergotamine was specially effective in children with vegetative lability. The secondary effects, 12% with dihydroergotamine and 20% with flunarizine, were trivial and advantageous even, without the necessity of stop the treatment in not any case. The clinical efficacy of flunarizine and propranolol for the prevention of migraine attacks was assessed in 33 children in a double blind study. After a run-in phase of one month, 32 patients started the active medication. A reduction in the number of migraine attacks was observed in 75% of the flunarizine group and in 73.8% of the propranolol group. Propranolol also reduced the severity of attacks. Transient side effects were observed in 3 of 17 of the flunarizine group and in 5 of 15 of the propranolol group. The most frequent side effect was increased fatigue, which required interruption of therapy in 2 patients of the propranolol group. An 8-month, double-blind, placebo-controlled, crossover trial of flunarizine in the prophylaxis of migraine has been performed in 70 children. After 4 weeks of medication-free base-line observation, 35 children (group A) received flunarizine (5 mg/day) and 35 (group B) received placebo over a 12-week period. After a 4-week washout they crossed treatments for another 12 weeks. Sixty-three patients completed the trial. In both groups flunarizine significantly reduced the frequency and average duration of headache attacks. In group A efficacy was maintained after placebo crossover for the last 4 months of the study. Five subjects in group B stopped placebo because of ineffectiveness; two children in group A discontinued flunarizine treatment, one because of excessive daytime sedation and the other because therapy was ineffective. The main side effects were daytime sedation and weight gain. It is concluded that flunarizine is an effective drug for the treatment of childhood migraine. In a study of this length no serious side effects were discovered. nan Forty-seven children with migraine have been included in a double-blind cross-over study with pizotifen and placebo. The children received either pizotifen for 3 months followed by placebo or vice versa. Thirty-nine children completed the trial and there was no significant difference between active and placebo treatment as regards reduction of number of attacks, total and mean duration of attacks and duration of longest attacks. Pizotifen was well tolerated by the children. In a prospective study we compared propranolol, placebo, and self-hypnosis in the treatment of juvenile classic migraine. Children aged 6 to 12 years with classic migraine who had no previous specific treatment were randomized into propranolol (at 3 mg/kg/d) or placebo groups for a 3-month period and then crossed over for 3 months. After this 6-month period, each child was taught self-hypnosis and used it for 3 months. Twenty-eight patients completed the entire study. The mean number of headaches per child for 3 months during the placebo period was 13.3 compared with 14.9 during the propranolol period and 5.8 during the self-hypnosis period. Statistical analysis showed a significant association between decrease in headache frequency and self-hypnosis training (P = .045). There was no significant change in subjective or objective measures of headache severity with either therapy. In a double-blind crossover study of 39 children with established migraine, there was no difference between treatment with propanolol and placebo as regards frequency, severity or average duration of migraine attacks. There was some evidence that propanolol increased the average length of headaches. nan nan L-5HTP was tested versus placebo in a double-blind crossover study of 27 migraine children aged 6-12 years, who recorded their headaches in a headache diary for 1 month. Twenty-one patients subsequently started the trial. The mean daily dose of L-5HTP was 5 mg/kg body weight, and each treatment period with either L-5HTP or placebo lasted 12 weeks. In group A (L-5HTP-placebo; 10 patients) and group B (placebo-L-5HTP; 11 patients) both L-5HTP and placebo led to a significant reduction of the migraine index and frequency of migraine attacks during the 3rd month of each treatment period. However, we found a treatment X period interaction because the efficacy determinants decreased significantly during the first and the second treatment periods in both groups irrespective of the sequence of treatments. No differences were found between L-5HTP (first period of group A) and placebo (first period of group B). 30 children between 7 and 17 years suffering from at least 2 attacks/month of common or classical migraine since more than 1 year were studied. After clinical exclusion of symptomatic headache 4 weeks were documented by means of a migraine diary. Prophylaxis with Calcium entry blocker Flunarizine (Sibelium) or Thromboxane A inhibitor Acetylsalicylic acid (ASS) was carried out in a double blind design for 3 months. Medication was given as one dosage in the evening: 2-5 mg/kg KG ASS or 5-10 mg Flunarizine. Documented attack frequency and duration were controlled at monthly physical examinations. Final results showed no differences in significant reduction of attack frequency or symptoms between both different therapeutic principals. 72.4% (ASS 73.3%; Flunarizine 71.4%) of patients were attack-free or had at least a 50% reduction. Migraine frequency of initially 7-8 was reduced to 1-2 attacks/month. Duration remained constant in both groups (1-3 h). Side effects were slight body weight gain or abdominal pain after intake, prophylaxis had not to be interrupted therefore. Longtime prognosis is not yet possible because the time of observation is too short so far. Conclusion: Both substances are definitely useful and have few side effects in childhood migraine. If the response to one is insufficient the other substance should be tried. Thirty patients (mean age: 10.38 years) affected by primary headache were selected for a double-blind cross-over clinical trial. The patients were randomized into 2 homogeneous groups of 15 and treated for 12 weeks with L-5-HTP (100 mg/day) and placebo as per the following design: placebo - L-5-HTP (group A) and L-5-HTP - placebo (group B). Evaluation was carried out every 3 weeks by the Migraine Index supplying a general assessment of the attacks, i.e. severity, duration and frequency. The decrease in mean score values was directly proportional to L-5-HTP treatment, and statistical significance (Wilcoxon's test) was observed only for L-5-HTP in both groups, from 0.05 to 0.01. Improvement, as evaluated by CGI on percentage distribution of the patients, was homogeneous in both groups. A daily dose of papaverine (5--10 mg per kg body weight) was administered on a double-blind basis for two months to 42 successive child patients suffering from migraine or other vascular headache attacks not less than twice a month. Thirty-seven patients received the drug for the whole period of two months and 31 of these could be followed for a period of one to 10 months (mean 4.5 months) after the cessation of the treatment. Nineteen received papaverine and 18 placebo. Six out of 19 papaverine patients and none of 18 placebo patients were completely free from attacks during the treatment. Altogether 11 patients in the papaverine group and 5 in the placebo group experienced a 75--100% reduction in attack frequency which was accompanied by lower intensity and shorter duration of attacks. The results were best in cases with classical migraine. An "excellent" or "good" drug effect was experienced by 58% of papaverine patients and 17% of placebo patients.
Only one study each for propranolol and flunarizine were identified showing efficacy of these drugs as prophylactics of paediatric migraine. Nimodipine, timolol, papaverine, pizotifen, trazodone, L-5HTP, clonidine, metoclopramide, and domperidone showed no efficacy in reduction of frequency of attacks. Available studies on other commonly used drugs failed to meet our inclusion criteria. The quality of evidence available for the use of drug prophylaxis in paediatric migraine was poor. Studies were generally small, with no planning of sample size, so that for many drugs, despite the negative findings of this review, we do not have conclusive evidence of 'no effect'. There is a clear and urgent need for methodologically sound RCTs for the use of prophylactic drugs in paediatric migraine, starting with propranolol. These studies need to be adequately powered to investigate meaningful reductions in pain and suffering from a patient's perspective.