A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.
OBJECTIVE
This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.


METHODS
This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.


RESULTS
Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.


CONCLUSIONS
While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.
Potkin
Steven G
SG
University of California, Irvine, Orange, 92696, USA. sgpotkin@uci.edu
Gharabawi
Georges M
GM
Greenspan
Andrew J
AJ
Mahmoud
Ramy
R
Kosik-Gonzalez
Colette
C
Rupnow
Marcia F T
MF
Bossie
Cynthia A
CA
Davidson
Michael
M
Burtea
Victoria
V
Zhu
Young
Y
Trivedi
Jintendra K
JK
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000534:rehabilitation*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone