Risperidone in treatment-refractory schizophrenia

Objective: The purpose of this study was to evaluate the clinical safety an d efficacy of risperidone compared to haloperidol in patients with treatmen t-refractory schizophrenia. Method: Sixty-seven medication-unresponsive sub jects were randomly assigned to treatment with risperidone (N=34) or halope ridol (N=33), After a 3-7 day-placebo washout period, there was a 4-week, d ouble-blind, fixed-dose comparison trial that was followed by a 4-week, fle xible-dose phase. Measures of clinical change were quantified by standard p sychopathologic and neuromotor instruments. Results: Risperidone demonstrat ed clinical efficacy superior to that of haloperidol on the total Brief Psy chiatric Rating Scale (BPRS) after the first 4 weeks of treatment, Risperid one did not show any advantage over haloperidol after an additional 4 weeks . Overall improvement on the BPRS at 4 weeks was significantly better for t he risperidone group (24%) than for the haloperidol group (11%). Risperidon e-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (2 0% versus 63%); they also had significantly less observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia, Baseline char acteristics that correlated significantly with risperidone response were po sitive symptoms, conceptual disorganization, akathisia, and tardive dyskine sia. Conclusions: Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psycho tic symptoms and extrapyramidal side effects at baseline appear to be power ful predictors of subsequent response to risperidone.