A Double-blind Placebo-controlled Discontinuation Study of Zuclopenthixol for the Treatment of Aggressive Disruptive Behaviours in Adults with Mental Retardation – Secondary Parameter Analyses

Abstract

Earlier studies showed risperidone to be effective in the treatment of aggression and self-injurious behaviour in adults with mental retardation but also having adverse side effects. This study was conducted to evaluate the effects of zuclopenthixol withdrawal. After open treatment with zuclopenthixol (n=49) responders were randomly assigned to continue (n=19) or discontinue (n=20) zuclopenthixol treatment during a 12-week double-blind, placebo-controlled period. Effects were measured using the Disability Assessment Schedule (DAS), improvement on the Clinical Global Impression Scale (CGI-I), and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). Ten patients (20%) discontinued the study due to insufficient therapeutic effect or adverse events in the open period. The superiority of zuclopenthixol over placebo among all randomized patients was supported not only by primary efficacy measure but also by the comparisons of mean scores of all secondary efficacy measures tested in a step-down-procedure (DAS, p<0.001; CGI-I, p<0.002, NOSIE, p<0.005). In both groups, one patient discontinued (5%) for adverse events. Adverse events were generally mild or moderate in severity. Zuclopenthixol proved to be safe and effective to keep a low rate of aggressive behaviour in adults with mental retardation.