PIRACETAM RELIEVES SYMPTOMS IN PROGRESSIVE MYOCLONUS EPILEPSY - A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, CROSSOVER STUDY COMPARING THE EFFICACY AND SAFETY OF 3 DOSAGES OF ORAL PIRACETAM WITH PLACEBO

Objective-To compare the efficacy, tolerability, and safety of three d aily dosage regimens of oral piracetam in patients with progressive my oclonus epilepsy. Methods-Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design i n which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piraceta m, given in two divided doses, were compared with placebo. The crossov er design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatme nt period of six weeks and thus without wash out between each treatmen t phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disa bility, handwriting, and global assessments by investigators and patie nts were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day. Results- Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02 ), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement i n functional disability was also found with daily doses of 9.6 g and 1 6.8 g. The dose-effect relation was Linear and significant. More patie nts showed clinically relevant improvement with the highest dosage and , in individual patients, increasing the dose improved response. Pirac etam was well tolerated and adverse effects were few, mild, and transi ent. Conclusions-This study provides further evidence that piracetam i s an effective and safe medication in patients with Unverricht-Lundbor g disease. In addition, it shows that a dose of 24 g is highly benefic ial, more effective than lower doses and that a dose-effect relation e xists. There is considerable variation in optimal individual dosage.