Efficacy of Quetiapine vs Haloperidol and Placebo in the Short-term Treatment of Acute Schizophrenia S Charles Schulz, MD Serequel® is a trademark, the property of the AstraZeneca group of companies
Department of Psychiatry, Medical School, University of Minnesota, USA
Abstract Introduction :
The efficacy of quetiapine in relieving the
positive and negative symptoms of schizophrenia has been demonstrated in a number of controlled and open-label extension studies. The objective of this analysis was to compare the efficacy of quetiapine with existing treatment
Results
Table 3.Response rates for haloperidol-controlled trials
Demographic details
Study Study numbe numberr
Treatme reatment nt
Study 13
Haloperidol
10
42
19%
Quetiapine
54
151
26%
Haloperidol
107
120
47%
Quetiapine
101
120
46%
Haloperidol
40
148
21%
Quetiapine
61
132
32%
Haloperidol
37
104
26%
Quetiapine
53
87
38%
v
and 80% were white. v
The predominant diagnoses were paranoid (60%) and undifferentiated (25%) schizophrenia.
options by performing a meta-analysis on data from six
Study 14
studies in which quetiapine was compared with haloperidol and placebo in the short-term treatment of acute
The proportion of patients who experienced a
clinically relevant response to treatment (>40% reduction in
Study 50 Trial Trial (dosing (dosing approach) approach) Treatmen Treatmentt group group
Patients Patients randomize randomized d Study 52
Trial rial 6 (flexib flexible le dose) dose)
the Brief Psychiatric Rating Scale [0–6] score from baseline
Quet Quetia iapin pine e (up to 750 750 mg/da mg/day y
54
Placebo
55 v
to endpoint) was calculated for each treatment, within each Quetiapin Quetiapine e low dose (up to 250 mg/ day)
94
Quetiapine high dose (up to 750 mg/ day)
96
Placebo
96
Quet iapine 75 mg
53
Quet iapine 150 mg
48
Quet iapine 300 mg
52
heterogeneity of treatment effect between trials (p=0.183).
Quet iapine 600 mg
51
The combined OR for quetiapine vs placebo was 2.31 (95%
Quet iapine 750 mg
CI: 1.50, 3.56; p<0.001), and for quetiapine vs haloperidol
Placebo
51
was 1.32 (95% CI: 1.04, 1.68; p=0.020).
Haloperidol 12 mg
52
trial. The homogeneity of treatment effects across studies
Trial 8 (flexible (flexible dose)
was assessed. The combined odds ratio (OR) and associated 95% confidence interval were calculated, with an OR >1 indicating superiority of quetiapine over
The response rates in the individual trials ranged
Trial 13 (fixed dose)
from 26–43% for quetiapine, 19–47% for haloperidol, and 6–25% for placebo. There was no indication of
Conclusions:
In the short-term treatment of acute
Trial rial 14 (flex (flexible ible dose) dose)
schizophrenia, quetiapine is significantly superior to
221
Halo Halope peri rido doll (up to 16 mg/da mg/day) y)
227 227
Figure 1. Quetiapine vs placebo: meta-analysis of Trials 6,8 and 13 BPRS responders. responders. Odds ratio and 95% confidence interval. 20 19 18 o ti ra s d d o d e n i b m o C
Queti Quetiapi apine ne (up (up to 600 600 mg/day mg/day))
193
Halo Halope peri rido doll (up to 20 mg/da mg/day) y)
188 188
Quet ia iap in ine (60 0 mg /d /d ay ay )
14 3
Haloperidol (20 mg/ day
145
haloperidol and placebo in terms of clinically relevant response rates. This would suggest that quetiapine is a
Trial rial 50 (flex (flexible ible dose) dose)
first-choice antipsychotic.
v
Tr ia ial 52 (f ix ix ed ed d os os e) e)
Methods
Tot al
Multicenter, 6-week (12-week for Trial 50), double-blind, randomized, placebo- or haloperidol-controlled trials.
Study Study numbe numberr
Treatm reatment ent
v
Men and women, 18 years and older, hospitalized with
Study 6
Plac ebo
acute exacerbation of chronic or subchronic
Patient Patient respo respons nse e (n) (n) Yes No 14
41
Study 8
Percen Percentag tage e responding
St ud ud y 1 2
Co mb mb ine d analysis
The combined odds ratio for response rate for quetiapine There was no indication of heterogeneity of treatment
3.5
3.0
25%
Quetiapine
23
31
43%
Plac ebo
19
77
20%
Quetiapine
56
134
30%
Plac ebo
3
48
6%
Quetiapine
54
151
26%
o ti 2.5 ra s d d 2.0 o d e n i b 1.5 m o C
No significant clinical disorder or laboratory or ECG abnormalities.
St ud ud y 8
effect between trials (p=0.1823).
schizophrenia (DSM-III-R or DSM-IV). v
St ud ud y 6
Figure 2. Quetiapine vs haloperidol: meta-analysis of t rials 13,14, 50 and 52 BPRS responders. Odds ratio and 95% confidence interval.
t able 2.Response rates for placebo- controlled trials T
Population
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
vs placebo was 2.31 (95% CI: 1.50, 3.56; p<0.001). v
1873
Design v
Within each trial, the response rate was higher for quetiapine compared to haloperidol in 3 of 4 trials .
54
Queti Quetiapi apine ne (up (up to 800 800 mg/day mg/day))
Response rates ranged from 19–47% for haloperidol and from 26–46% for quetiapine.
v
haloperidol or placebo. Results:
Percen Percentage tage responding
Table 1. Addit ional trial details
schizophrenia. Methods:
Patient Patient respo respons nse e (n) (n) Yes No
Patient age ranged from 18 to 75 years; 71% were men
1.0 0.5
Analysis
Study 13
0.0
Study Study 13
v
Primary efficacy variables: Brief Psychiatric Rating Scale
Study Study 14
Study Study 50
Study Study 52
Combin Combined ed analysis
(BPRS) total score or Positive and Negative Syndrome Scale (PANSS) score. v
v
A clinically relevant response (improvement) rate was defined as a ≥40% reduction from baseline baseline to endpoint in
Response rates ranged from 6–25% for placebo and from
v
26–43% for quetiapine. v
BPRS total score or derived PANSS score (using
Within each trial, the response rate was always higher for
vs haloperidol was 1.32 (95% CI: 1.04, 1.68; p=0.02). v
patients treated with quetiapine.
There was no indication of heterogeneity of treatment effect between trials (p=0.141).
symptoms that matched the BPRS; Trials 14, 50, and 52). v
The combined odds ratio for response rate for quetiapine
For each trial, the proportion of patients who achieved a clinically relevant response was calculated for each treatment. These proportions were compared within
Conclusions
study using odds ratios (with 95% confidence intervals).
v
After checking that there was no between-study
Meta-analysis is a strong statistical method for assessing
v
multiple trials and is especially superior to the ‘ box score’
heterogeneity in the study conclusions, the odds
method. In addition, it allows for quantification of differences
ratios were combined across the studies for an
between conditions.
placebo (p<0.001) as well as to haloperidol (p=0.02) utilizing utilizing the 40% reduction of rated behavior as a criterion. v
overview analysis. v
In this analysis, quetiapine was clearly statistically superior to
These results results support quetiapine as a first-line atypic al antipsychotic medication.
Odds ratios greater than 1 indicated a significantly higher rate of response for quetiapine compared with placebo or haloperidol. haloperidol. If the lower limit of t he 95% confidence interval for the overview analysis was greater than 1, this
References 1.
indicated that across the studies, a significantly greater proportion of patients responded to quetiapine, compared with placebo or haloperidol.
2.
Borison RL, RL, Arvanitis tis LA, Miller ler BG, and and the US Seroquel Seroquel Study Study Group. ICI 204,636, 204,636, an
3.
Arvanitis tis LA, Miller ler BG, and and the Seroquel Trial al 13 Study Group. Group. Multiple fixed doses doses of
atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients
"Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: schizophrenia: a comparison
with schizophrenia. J Clin Psychopharmac ol 1996;16:158–169.
with haloperidol and placebo. Biol Psychiatry 1997;42:233–246. 233–246.
Small JG, Hirsch SR, SR, Arvanitis LA, LA, Miller BG, BG, Link CGG, and and The Seroquel Seroquel Study Group. Quetiapine in patients with schizophrenia: schizophrenia: a high- and low-dose double-blind comparison with placebo . Arch Gen Psychiatry 1997;54:549–557.
4.
Copolov DL, DL, Link CGG, Kowalcyk B. A multicentre, multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, 'Seroquel') and haloperidol in schizophrenia. Psychol Med 2000;30(1):95–106.
