CYCLANDELATE IN THE PROPHYLAXIS OF MIGRAINE - A RANDOMIZED, PARALLEL,DOUBLE-BLIND-STUDY IN COMPARISON WITH PLACEBO AND PROPRANOLOL

Cyclandelate inhibits calcium-induced contraction of vascular smooth m uscle cells, platelet aggregation induced by thrombin, platelet-activa ting-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelat e may have a potential prophylactic effect in migraine. To test this h ypothesis, a double-blind multicentre study was performed in 214 patie nts to investigate the efficacy and tolerability of cyclandelate compa red to placebo and propranolol. After a 4-week baseline period, eligib le patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n=81), placebo (n=55) or 120 mg propr anolol (n=78). The number of migraine attacks (greater than or equal t o 50% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylacti c treatment. The percentage of patients with a reduction in migraine a ttacks of greater than or equal to 50% treated with cyclandelate (37.0 %) or propranolol (42.3%) was not significantly superior to placebo (3 0.9%; p>0.025). The mean duration of migraine in hours (h) per month d ecreased in both active treatment groups (cyclandelate: 36.8h, p=0.046 ; propranolol: 34.4 h, p=0.039) compared to placebo (13.7h) without re aching statistical significance (alpha/2=0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences w ere reported by 13 patients (16.0%) treated with cyclandelate, by 5 pa tients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n=6) of patients tr eated with cyclandelate and in 9% (n=7) of patients treated with propr anolol. In summary, cyclandelate has a comparable efficacy to that of propranolol, an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated.