Efficacy of Quetiapine vs Haloperidol and Placebo in

the Short-term Treatment of Acute Schizophrenia

S Charles Schulz, MD
Serequel® is a trademark,
Department of Psychiatry, Medical School, University of Minnesota, USA the property of the AstraZeneca
group of companies

Abstract Results Table 3. Response rates for haloperidol-controlled trials

Introduction: The efficacy of quetiapine in relieving the Demographic details Study number Treatment Patient response (n) Percentage
positive and negative symptoms of schizophrenia has been Yes No responding
Patient age ranged from 18 to 75 years; 71% were men

▲
demonstrated in a number of controlled and open-label Study 13 Haloperidol 10 42 19%
and 80% were white.
extension studies. The objective of this analysis was to Quetiapine 54 151 26%
The predominant diagnoses were paranoid (60%) and

▲
compare the efficacy of quetiapine with existing treatment
options by performing a meta-analysis on data from six undifferentiated (25%) schizophrenia. Study 14 Haloperidol 107 120 47%

studies in which quetiapine was compared with haloperidol Quetiapine 101 120 46%
Table 1. Additional trial details
and placebo in the short-term treatment of acute Study 50 Haloperidol 40 148 21%
schizophrenia. Quetiapine 61 132 32%
Trial (dosing approach) Treatment group Patients randomized
Methods: The proportion of patients who experienced a
Study 52 Haloperidol 37 104 26%
clinically relevant response to treatment (>40% reduction in Trial 6 (flexible dose) Quetiapine (up to 750 mg/day 54
Quetiapine 53 87 38%
the Brief Psychiatric Rating Scale [0–6] score from baseline Placebo 55
to endpoint) was calculated for each treatment, within each Response rates ranged from 19–47% for haloperidol and

▲
Trial 8 (flexible dose) Quetiapine low dose
trial. The homogeneity of treatment effects across studies from 26–46% for quetiapine.
(up to 250 mg/day) 94
was assessed. The combined odds ratio (OR) and
Within each trial, the response rate was higher for

▲
Quetiapine high dose
associated 95% confidence interval were calculated, with (up to 750 mg/day) 96 quetiapine compared to haloperidol in 3 of 4 trials.
an OR >1 indicating superiority of quetiapine over Placebo 96
haloperidol or placebo. Figure 1. Quetiapine vs placebo: meta-analysis of Trials 6,8 and 13 —
Trial 13 (fixed dose) Quetiapine 75 mg 53 BPRS responders. Odds ratio and 95% confidence interval.
Results: The response rates in the individual trials ranged
Quetiapine 150 mg 48
from 26–43% for quetiapine, 19–47% for haloperidol, and 20
Quetiapine 300 mg 52 19
6–25% for placebo. There was no indication of
18
Quetiapine 600 mg 51
heterogeneity of treatment effect between trials (p=0.183). 6.0

Combined odds ratio

Quetiapine 750 mg 54 5.5
The combined OR for quetiapine vs placebo was 2.31 (95% 5.0

CI: 1.50, 3.56; p<0.001), and for quetiapine vs haloperidol Placebo 51 4.5
4.0

was 1.32 (95% CI: 1.04, 1.68; p=0.020). Haloperidol 12 mg 52 3.5

3.0
2.5
Conclusions: In the short-term treatment of acute Trial 14 (flexible dose) Quetiapine (up to 800 mg/day) 221 2.0
1.5
schizophrenia, quetiapine is significantly superior to Haloperidol (up to 16 mg/day) 227 1.0
0.5
haloperidol and placebo in terms of clinically relevant 0.0
Study 6 Study 8 Study 12 Combined
Trial 50 (flexible dose) Quetiapine (up to 600 mg/day) 193
response rates. This would suggest that quetiapine is a analysis

first-choice antipsychotic. Haloperidol (up to 20 mg/day) 188

The combined odds ratio for response rate for quetiapine
▲

Trial 52 (fixed dose) Quetiapine (600 mg/day) 143

vs placebo was 2.31 (95% CI: 1.50, 3.56; p<0.001).
Haloperidol (20 mg/day 145
There was no indication of heterogeneity of treatment
▲

Methods Total 1873 effect between trials (p=0.1823).

Design Figure 2. Quetiapine vs haloperidol: meta-analysis of trials 13,14,

t 50 and 52 — BPRS responders. Odds ratio and 95%
Table 2. Response rates for placebo-controlled trials
Multicenter, 6-week (12-week for Trial 50), double-blind,
▲

confidence interval.
randomized, placebo- or haloperidol-controlled trials.
Study number Treatment Patient response (n) Percentage
3.5
Yes No responding
Population
3.0
Study 6 Placebo 14 41 25%
Men and women, 18 years and older, hospitalized with
▲

Combined odds ratio

2.5
Quetiapine 23 31 43%
acute exacerbation of chronic or subchronic
2.0
schizophrenia (DSM-III-R or DSM-IV).
Study 8 Placebo 19 77 20% 1.5

No significant clinical disorder or laboratory or ECG

▲

Quetiapine 56 134 30% 1.0

abnormalities.
0.5

Analysis Study 13 Placebo 3 48 6%

0.0
Study 13 Study 14 Study 50 Study 52 Combined
Quetiapine 54 151 26% analysis
Primary efficacy variables: Brief Psychiatric Rating Scale
▲

(BPRS) total score or Positive and Negative Syndrome

Scale (PANSS) score. Response rates ranged from 6–25% for placebo and from
▲

The combined odds ratio for response rate for quetiapine

▲

A clinically relevant response (improvement) rate was 26–43% for quetiapine.

▲

vs haloperidol was 1.32 (95% CI: 1.04, 1.68; p=0.02).

defined as a ≥40% reduction from baseline to endpoint in Within each trial, the response rate was always higher for
▲

There was no indication of heterogeneity of treatment

▲

BPRS total score or derived PANSS score (using patients treated with quetiapine. effect between trials (p=0.141).
symptoms that matched the BPRS; Trials 14, 50, and 52).
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).
Meta-analysis is a strong statistical method for assessing In this analysis, quetiapine was clearly statistically superior to
▲

After checking that there was no between-study multiple trials and is especially superior to the ‘box score’ placebo (p<0.001) as well as to haloperidol (p=0.02) utilizing
heterogeneity in the study conclusions, the odds method. In addition, it allows for quantification of differences the 40% reduction of rated behavior as a criterion.
ratios were combined across the studies for an between conditions. These results support quetiapine as a first-line atypical
▲

overview analysis. antipsychotic medication.

Odds ratios greater than 1 indicated a significantly higher
▲

rate of response for quetiapine compared with placebo or

haloperidol. If the lower limit of the 95% confidence
interval for the overview analysis was greater than 1, this
indicated that across the studies, a significantly greater
proportion of patients responded to quetiapine,
compared with placebo or haloperidol.
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