Risperidone in treatment-refractory schizophrenia

Donna A. Wirshing, Barringer D. Marshall, Michael F. Green, Jim Mintz, Stephen R. Marder, William C. Wirshing

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Objective: The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. Method: Sixty-seven medication- unresponsive subjects were randomly assigned to treatment with risperidone (N=34) or haloperidol (N=33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. Results: Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol- treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly less observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. Conclusions: Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.

Original languageEnglish (US)
Pages (from-to)1374-1379
Number of pages6
JournalAmerican Journal of Psychiatry
Issue number9
StatePublished - Sep 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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