Clozapine alone versus clozapine and risperidone with refractory schizophrenia.
BACKGROUND
The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known.


METHODS
In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning.


RESULTS
A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, -7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups.


CONCLUSIONS
In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584).
Honer
William G
WG
Centre for Complex Disorders and the Department of Psychiatry, University of British Columbia, Vancouver General Hospital Research Pavilion, Vancouver, Canada. honer@interchange.ubc.ca
Thornton
Allen E
AE
Chen
Eric Y H
EY
Chan
Raymond C K
RC
Wong
Jessica O Y
JO
Bergmann
Andrea
A
Falkai
Peter
P
Pomarol-Clotet
Edith
E
McKenna
Peter J
PJ
Stip
Emmanuel
E
Williams
Richard
R
MacEwan
G William
GW
Wasan
Kishor
K
Procyshyn
Ric
R
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D017211:Treatment Failure
D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone