Risperidone in treatment-refractory schizophrenia.
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.


METHODS
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 les 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.
Wirshing
D A
DA
Department of Psychiatry, VA Greater Los Angeles Healthcare System, CA 90073, USA.
Marshall
B D
BD
Green
M F
MF
Mintz
J
J
Marder
S R
SR
Wirshing
W C
WC
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000517:prevention & control; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D010919:Placebos; D006220:Haloperidol; D018967:Risperidone