Double-blind study of cyamemazine and diazepam in the alcohol withdrawal syndrome.

Author(s): Favre JD, Allain H, Aubin HJ, Frija-Orvoen E, Gillet C, Lejoyeux M, Payen A, Weber M, Garcia-Acosta S, Kermadi I, Dib M

Affiliation(s): Service de Psychiatrie, Hopital d'Instruction des Armees Percy, Clamart, France.

Publication date & source: 2005-10, Hum Psychopharmacol., 20(7):511-9.

Publication type: Multicenter Study; Randomized Controlled Trial

OBJECTIVE: Cyamemazine is an original phenothiazine derivative which showed similar efficacy and tolerability to lorazepam during ethanol withdrawal in mice. This study investigated cyamemazine for its efficacy and tolerability in alcohol-dependent patients electing an alcohol withdrawal procedure, in comparison with diazepam. METHOD: A multicenter, randomized, double-blind study in 89 alcohol-dependent patients (CIWA-Ar score between 10 and 30), electing an alcohol withdrawal procedure, was used to find effective doses of cyamemazine and to compare it with diazepam for efficacy and tolerability. On day 1 (D(1)), cyamemazine or diazepam (50 mg and 10 mg capsule, respectively) were administered at hourly intervals to reduce CIWA-Ar = 5, up to a maximum of eight administrations. Starting from D(2), the compounds were given twice a day in progressively decreasing doses during a maximum period of 13 days (D(end)). RESULTS: At h(8) (8 h after the first treatment of D(1)), therapeutic success (CIWA-Ar score </= 5) was achieved in 32 out of 43 ITT patients treated with cyamemazine (74.4%), a value very similar to that of diazepam (32/44; 72.7%). Most such patients (29/32) were controlled with 2-6 capsules of cyamemazine (100-300 mg). In the PP population, cyamemazine (n = 28) was significantly non-inferior to diazepam (n = 33), with a threshold of 10% for non-inferiority bound and 2.5% for one-sided type I error rate. Such therapeutic similarity was confirmed by the analysis of other efficacy criteria. Safety analysis did not show substantial differences between the two treatments. CONCLUSIONS: Cyamemazine showed similar efficacy and tolerability to diazepam for the treatment of alcohol withdrawal symptoms at therapeutic doses in the range 100-300 mg. Copyright (c) 2005 John Wiley & Sons, Ltd.