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S Charles Schulz, MD Department of Psychiatry, Medical School, University of Minnesota, USA
Serequel® is a trademark, the property of the AstraZeneca group of companies
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
Table 3. Response rates for haloperidol-controlled trials Study number Treatment Patient response (n) Yes No 10 54 107 101 40 61 37 53 42 151 120 120 148 132 104 87 Percentage responding 19% 26% 47% 46% 21% 32% 26% 38%
Patient age ranged from 18 to 75 years; 71% were men and 80% were white. The predominant diagnoses were paranoid (60%) and undifferentiated (25%) schizophrenia.
Study 14 Study 13 Haloperidol Quetiapine Haloperidol Quetiapine
compare the efficacy of quetiapine with existing treatment options by performing a meta-analysis on data from six studies in which quetiapine was compared with haloperidol and placebo in the short-term treatment of acute schizophrenia. Methods: The proportion of patients who experienced a clinically relevant response to treatment (>40% reduction in the Brief Psychiatric Rating Scale [0–6] score from baseline to endpoint) was calculated for each treatment, within each trial. The homogeneity of treatment effects across studies was assessed. The combined odds ratio (OR) and associated 95% confidence interval were calculated, with an OR >1 indicating superiority of quetiapine over haloperidol or placebo. Results: The response rates in the individual trials ranged from 26–43% for quetiapine, 19–47% for haloperidol, and 6–25% for placebo. There was no indication of heterogeneity of treatment effect between trials (p=0.183). The combined OR for quetiapine vs placebo was 2.31 (95% CI: 1.50, 3.56; p<0.001), and for quetiapine vs haloperidol was 1.32 (95% CI: 1.04, 1.68; p=0.020). Conclusions: In the short-term treatment of acute schizophrenia, quetiapine is significantly superior to haloperidol and placebo in terms of clinically relevant response rates. This would suggest that quetiapine is a first-choice antipsychotic.
Table 1. Additional trial details Study 50 Trial (dosing approach) Treatment group Trial 6 (flexible dose) Patients randomized Study 52 Quetiapine (up to 750 mg/day Placebo Trial 8 (flexible dose) Quetiapine low dose (up to 250 mg/day) Quetiapine high dose (up to 750 mg/day) Placebo Trial 13 (fixed dose) Quetiapine 75 mg Quetiapine 150 mg Quetiapine 300 mg Quetiapine 600 mg Quetiapine 750 mg Placebo Haloperidol 12 mg Trial 14 (flexible dose) Quetiapine (up to 800 mg/day) Haloperidol (up to 16 mg/day) Trial 50 (flexible dose) Quetiapine (up to 600 mg/day) Haloperidol (up to 20 mg/day) Trial 52 (fixed dose) Quetiapine (600 mg/day) Haloperidol (20 mg/day 54 55 Haloperidol Quetiapine
Response rates ranged from 19–47% for haloperidol and from 26–46% for quetiapine. Within each trial, the response rate was higher for quetiapine compared to haloperidol in 3 of 4 trials.
96 96 53 48
Figure 1. Quetiapine vs placebo: meta-analysis of Trials 6,8 and 13 — BPRS responders. Odds ratio and 95% confidence interval.
52 51 54 51 52 221 227 193 188
Combined odds ratio
19 18 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
The combined odds ratio for response rate for quetiapine vs placebo was 2.31 (95% CI: 1.50, 3.56; p<0.001). There was no indication of heterogeneity of treatment effect between trials (p=0.1823).
143 145 1873
Multicenter, 6-week (12-week for Trial 50), double-blind, randomized, placebo- or haloperidol-controlled trials.
t Table 2. Response rates for placebo-controlled trials
Study number Treatment Patient response (n) Yes No 14 23 41 31 Percentage responding 25%
Figure 2. Quetiapine vs haloperidol: meta-analysis of trials 13,14, 50 and 52 — BPRS responders. Odds ratio and 95% confidence interval.
Combined odds ratio
v v v v v v v
3.0 2.5 2.0 1.5 1.0 0.5
Men and women, 18 years and older, hospitalized with acute exacerbation of chronic or subchronic schizophrenia (DSM-III-R or DSM-IV).
Study 8 Placebo Quetiapine 19 56 77 134 20% 30% 43%
No significant clinical disorder or laboratory or ECG abnormalities.
Primary efficacy variables: Brief Psychiatric Rating Scale (BPRS) total score or Positive and Negative Syndrome Scale (PANSS) score. A clinically relevant response (improvement) rate was defined as a ≥40% reduction from baseline to endpoint in BPRS total score or derived PANSS score (using 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 study using odds ratios (with 95% confidence intervals). After checking that there was no between-study heterogeneity in the study conclusions, the odds ratios were combined across the studies for an overview analysis. 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.
Response rates ranged from 6–25% for placebo and from 26–43% for quetiapine. Within each trial, the response rate was always higher for patients treated with quetiapine.
Meta-analysis is a strong statistical method for assessing multiple trials and is especially superior to the ‘box score’ method. In addition, it allows for quantification of differences between conditions. In this analysis, quetiapine was clearly statistically superior to placebo (p<0.001) as well as to haloperidol (p=0.02) utilizing the 40% reduction of rated behavior as a criterion. These results support quetiapine as a first-line atypical antipsychotic medication.
Borison RL, Arvanitis LA, Miller BG, and the US Seroquel Study Group. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmacol 1996;16:158–169. Small JG, Hirsch SR, Arvanitis LA, Miller BG, Link CGG, and The Seroquel Study Group. Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry 1997;54:549–557. 3. Arvanitis LA, Miller BG, and the Seroquel Trial 13 Study Group. Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997;42:233–246. Copolov DL, Link CGG, Kowalcyk B. A multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, 'Seroquel') and haloperidol in schizophrenia. Psychol Med 2000;30(1):95–106.
The combined odds ratio for response rate for quetiapine vs haloperidol was 1.32 (95% CI: 1.04, 1.68; p=0.02). There was no indication of heterogeneity of treatment effect between trials (p=0.141).