Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily. Flunarizine vs. propranolol in the prophylaxis of migraine: two double-blind comparative studies in more than 400 patients. Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine. A comparative trial of flunarizine and propranolol in the prevention of migraine. Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study. Flunarizine and propranolol in the treatment of migraine. [The treatment of juvenile migraine using flunarizine or propranolol]. Valproate versus flunarizine in migraine prophylaxis: a randomized, double-open, clinical trial. Prophylactic antiemetic therapy with patient-controlled analgesia: a double-blind, placebo-controlled comparison of droperidol, metoclopramide, and tropisetron.
This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe. In the course of a 16 weeks' interval treatment of migraine in connection with two multicenter double-blind studies, flunarizine was compared with propranolol in patients suffering predominantly from "classical migraine". Eighty-seven patients from 12 outpatient departments were admitted to the first study, while 434 patients from 99 medical practices participated in the second study. After each month of treatment, the patients were clinically evaluated, and the number, duration, and severity of attacks were documented. Concerning the frequency and intensity of attacks, additional analgesics consumption and overall evaluation, both drugs proved to be highly effective in the practice as well as in the hospital study. The percentage and severity of side-effects were comparable in the two treatment groups. Summarizing, it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine. This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51% of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile. The calcium-entry blocker flunarizine (Sibelium; Janssen) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine. Fifty-eight patients were entered into a double-blind 4-month treatment trial. Patients in whom beta-blockers were contraindicated were excluded from the trial. At the end of the trial 28 patients had received 10 mg flunarizine at night during the study, 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn. Both groups responded well; and there was a 4-fold drop in frequency of attacks. There was no significant difference between the two groups in terms of patient profile, onset of response to therapy, final response to therapy, incidence of dropout from the trial or incidence of side-effects. Side-effects for flunarizine were weight gain (9 patients) and tiredness (6), and for propranolol sleep disturbances including nightmares (6), tiredness (8), mental changes (e.g. irritability) (3) and weight gain (4). Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs. The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis. In a double-blind, cross-over multicentre trial, the prophylactic antimigraine effect of the beta 1-selective beta-blocker metoprolol was evaluated and compared with that of the non-selective beta-blocker propranolol. Metoprolol was used in a dosage of 50 mg b.i.d. and propranolol in 40 mg b.i.d. 56 patients with classical or common migraine were included in the double-blind part of the investigation. 3 patients withdrew, but none because of side-effects. The data suggest that metoprolol is clinically equivalent in effectiveness to propranolol in migraine prophylaxis regarding parameters such as attack frequency, improvement in sum of severity score and subjective evaluation. Both drugs were generally well tolerated and the number of reported side-effects was similar to those reported during the run-in period (placebo). The clinical efficacy of flunarizine and of propranolol for the prevention of migraine attacks was assessed in a multicenter double-blind study lasting four months which was preceded by a single-blind placebo period of one month. For both drugs, more than half of the patients judged the effect to be good or very good. When considering the patients' daily logs, both drugs produced a significant reduction of the number of attacks. Propranolol furthermore significantly reduced the severity of attacks and the number of analgesics used during the attacks. In both groups no severe side effects were observed. 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. The aim of this study was to compare the efficacy and safety of valproate versus flunarizine in migraine prophylaxis in a randomized double-open clinical trial. Twenty-two migraine sufferers were treated with valproate (1 g per day) for 8 weeks; a parallel group of 22 migraine sufferers was treated with flunarizine (10 mg per day). The main admission criterion was a minimum of 3 migraine (with, or without aura) attacks per month. The major clinical parameters evaluated were the frequency of headache attacks, the frequency of use of drugs for the acute management of migraine, the patients' opinion of treatment and the Hamilton anxiety and depression rating scales. During the study 3 patients dropped out (1 from the valproate and 2 from the flunarizine groups). Fifteen patients (71.4%) from the valproate group responded to therapy, compared to 14 patients (65%) from the flunarizine group. In the valproate group 12 patients (57.1%) reported various side effects (prevalently gastric symptoms) versus 10 patients (47.6%) in the flunarizine group (prevalently somnolence). The patients who were treated with flunarizine showed an increase in the mean score of the 21-item Hamilton rating scale for depression, but the difference was not significant; morning dysthymia however, was significantly more often observed in the flunarizine patients, compared to the valproate patients. These results suggest that both drugs are effective and safe in migraine prophylaxis. This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (i.v.) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT3) antagonist was given as a single i.v. dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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.