Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.
ABSTRACT The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.
In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.
Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.
Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.
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ABSTRACT: It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate–severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100 mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100 mg, would be more effective than RLAI, 50 mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone + 9-hydroxyrisperidone, during treatment with RLAI 100 mg, were comparable to those for 6–8 mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥ 50–100 mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥ six months.Schizophrenia Research 04/2014; 154(1-3). DOI:10.1016/j.schres.2014.02.015 · 4.43 Impact Factor
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ABSTRACT: Impairment in psychosocial functioning is a key feature in schizophrenia, but few studies have examined the relationship between improvements in symptoms and functioning. We examined the relationship between change in symptoms and change in functioning in a group of patients with treatment-resistant schizophrenia after 6 and 12 weeks of clozapine treatment. Participants were assessed prior to clozapine and again at 6 and 12-week on the 18-item Brief Psychiatric Rating Scale (BPRS) and the Social and Occupational Functioning Scale (SOFAS). Change scores in BPRS and SOFAS at 6 and 12-week post clozapine were calculated and the direct relationship was assessed via regression models. Forty-three participants were included in this study; age of sample was 42.1±12.7 years, with 31 (72.1%) male participants. At baseline, the mean BPRS total and SOFAS scores were 46.98±12.86 and 33.07±10.79, respectively. There were significant improvements in BPRS total and SOFAS scores at 6 weeks, but no significant differences between 6 and 12-week assessments. There was no significant change in negative symptoms at both follow-up assessments. At 6-week, change in symptoms was not correlated with change in functioning and while the relationship between change in symptoms and functioning was stronger at 12 weeks, none of the BPRS factors emerged as a significant predictor. The present study found that lower baseline SOFAS score was the most robust predictor for improvements in SOFAS at 6 and 12-weeks. There appears to be a “ceiling” for functional improvements on clozapine, but follow-up studies are needed to examine functional gains beyond 12 weeks.European Neuropsychopharmacology 10/2014; 24(10). DOI:10.1016/j.euroneuro.2014.08.003 · 5.40 Impact Factor
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ABSTRACT: The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode.