A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.
BACKGROUND
Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine.


METHODS
In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003.


RESULTS
Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels.


CONCLUSIONS
Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.
Anil Yağcioğlu
A Elif
AE
Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. eanil@hacettepe.edu.tr
Kivircik Akdede
Berna B
BB
Turgut
Tolga I
TI
Tümüklü
Mevhibe
M
Yazici
M Kâzim
MK
Alptekin
Köksal
K
Ertuğrul
Aygün
A
Jayathilake
Karu
K
Göğüş
Ahmet
A
Tunca
Zeliha
Z
Meltzer
Herbert Y
HY
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D010919:Placebos; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life / Q000523:psychology; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos; D011388:Prolactin; D003024:Clozapine; D018967:Risperidone