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. 2004;2004(2):CD000967.
doi: 10.1002/14651858.CD000967.pub2.

Quetiapine for schizophrenia

M Srisurapanont  1 , B Maneeton, N Maneeton
Affiliations

Quetiapine for schizophrenia

M Srisurapanont et al. Cochrane Database Syst Rev. 2004.

Abstract

Background: Quetiapine is an atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for the treatment of schizophrenia and other psychoses.

Objectives: To determine the effects of quetiapine for schizophrenia in comparison to placebo, and other antipsychotics.

Search strategy: Electronic searches of the Cochrane Schizophrenia Group's Register of Trials (February 2003), Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. We contacted AstraZeneca Pharmaceuticals for information regarding unpublished trials. The review was updated in February 2003.

Selection criteria: All randomised controlled trials where adults with schizophrenia or similar illnesses were assigned to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported.

Data collection and analysis: Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. We analysed data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI). Only homogeneous data were interpreted as favouring treatment or control. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics (NNH). We calculated relative risk (RR) for dichotomous data, and weighted mean differences (WMD) for continuous data.

Main results: Despite the fact that 3443 people were randomised in 12 quetiapine studies, there are almost no data on service utilisation, economic outcomes, social functioning and quality of life. Over half of those within the quetiapine versus placebo comparison were lost to follow up (53% quetiapine vs 61% placebo, n=716, 4RCTs, RR 0.84 CI 0.7 to 0.9, NNT 11 CI 7 to 55) so it is impossible to interpret any ratings of global or mental state within this comparison with confidence. People allocated quetiapine, however, did not have more movement disorders than those given placebo (n=395, 2 RCTs, RR needing medication for EPSE 0.62 CI 0.3 to 1.2). The same applies to the comparison of >/= 250 mg/day quetiapine with < 250 mg/day quetiapine (49% dropout >/= 250 mg/day vs 58% < 250 mg/day, n=1066, 3 RCTs, RR 0.84 CI 0.8 to 0.9, NNT 11 CI 7 to 29). It should be noted that two deaths occurred in the higher dose group (n=618, 1 RCT, RR 0.1 CI 0.0 to 2.1). When quetiapine was compared with typical antipsychotics, about 36% of both groups failed to complete the short-term studies (n=1624, 6 RCTs, RR 0.87 CI 0.8 to 1.0). Average change in global state was heterogeneous and equivocal (n=762, 3 RCTs, WMD in short term 0.19 CI 0.00 to 0.38, I squared 76%). Mental state measures were also equivocal (n=1247, RR not improved 0.97 CI 0.9 to 1.1) including specific measures of negative symptoms (n=305, 1 RCT, MD change in SANS short term 0.94 CI -0.2 to 2.0). Movement disorders were less prevalent for those allocated quetiapine (n=1117, 4 RCTs, RR needing medication for extrapyramidal adverse effects 0.47 CI 0.4 to 0.6, NNT 4 CI 4 to 5, I squared 88%). Dry mouth (n=649, 2 RCTs, RR short term 2.85 CI 1.5 to 5.6, NNH 17 CI 7 to 65) and sleepiness (n=959, 3 RCTs, RR 1.51 CI 1.1 to 2.2, NNH 18 CI 8 to 181) may also be more prevalent for people given quetiapine compared with the older drugs. In the quetiapine versus risperidone comparison, over 30% of people left the study before completion (n=728, 1 RCT, RR 0.94 CI 0.7 to 1.2). Four people, all treated with quetiapine, died during the study (n=728, 1 RCT, RR 2.86 CI 0.2 to 52.8). Continuous mental state measures did not show clear differences between the two drugs (n=637, 1 RCT, MD PANSS 1.2 CI -2.0 to 4.4). However, considerably fewer people given quetiapine needed medication for extrapyramidal side effects compared with those allocated to risperidone (n=712, 1 RCT, RR 0.27 CI 0.2 to 0.5, NNT 11 CI 10 to 16). Quetiapine caused more dizziness (n=728, 1 RCT, RR 1.85 CI 1.0 to 3.3, NNH 18 CI 7 to 487), more dry mouth (n=728, 1 RCT, RR 2.11 CI 1.2 to 3.8, NNH 14 CI 6 to 82) and more sleepiness than risperidone (n=728, 1 RCT, RR 2.03 CI 1.4 to 2.9, NNH 7 CI 4 to 17).

Reviewers' conclusions: Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas.

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Conflict of interest statement

In the past five years Manit Srisurapanont has received honoraria and support for attending national and international scientific meetings from AstraZeneca (Thailand), Eli Lilly Asia, Inc. (Thailand), GlaxoSmithKline (Thailand), Janssen‐Cilag (Thailand), Servier (Thailand) and Solvay Pharmaceuticals (Thailand). Narong Maneeton and Benjaluk Maneeton have received similar support for attending national scientific meetings from GlaxoSmithKline (Thailand) and Janssen‐Cilag (Thailand).

Figures

1.1
1.1. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 1 Leaving the study early.
1.2
1.2. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 2 Global state: 1. No important improvement (CGI).
1.3
1.3. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 3 Global state: 2. Average change (CGI, low score = good).
1.4
1.4. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 4 Mental state: 1. No clinically important change (BPRS or PANSS).
1.5
1.5. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 5 Mental state: 2. Average change (BPRS, low score = good).
1.6
1.6. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 6 Mental state: 3. Average change in positive symptoms (BPRS positive subscale, low score = good).
1.7
1.7. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 7 Mental state: 4. Average change in negative symptoms (low score = good).
1.8
1.8. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 8 Adverse effects: 1. Movement disorders.
1.9
1.9. Analysis
Comparison 1 QUETIAPINE (any dose) versus PLACEBO (all short‐term data), Outcome 9 Adverse effects: 2. General.
2.1
2.1. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 1 Leaving the study early.
2.2
2.2. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 2 Death (any cause, any dose).
2.3
2.3. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 3 Global state: 1. No important improvement (CGI).
2.4
2.4. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 4 Global state: 2. Average change (CGI, low score = good).
2.5
2.5. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 5 Mental state: 1. No important improvement (BPRS or PANSS).
2.6
2.6. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 6 Mental state: 2. Average change (BPRS, low score = good).
2.7
2.7. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 7 Mental state: 3. Average change in positive symptoms (BPRS positive subscale, low score = good).
2.8
2.8. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 8 Mental state: 4. Average change in negative symptoms (low score = good).
2.9
2.9. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 9 Adverse effects: 1. Movement disorders.
2.10
2.10. Analysis
Comparison 2 >/= 250 mg/day QUETIAPINE versus < 250 mg/day QUETIAPINE ‐ all short term data, Outcome 10 Adverse effects: 2. General.
3.1
3.1. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 1 Leaving the study early: 1. Short‐term.
3.2
3.2. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 2 Leaving the study early: 2. Medium‐term.
3.3
3.3. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 3 Global state: Average change (CGI, low score = good).
3.4
3.4. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 4 Mental state: 1. No important improvement (BPRS or PANSS) ‐ short term only.
3.5
3.5. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 5 Mental state: 2. Average change (low score = good).
3.6
3.6. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 6 Mental state: 3. Average change in positive symptoms (low score = good).
3.7
3.7. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 7 Mental state: 4. Average change in negative symptoms (low score = good).
3.8
3.8. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 8 Adverse effects: 1. Movement disorders.
3.9
3.9. Analysis
Comparison 3 QUETIAPINE (any dose) versus CLASSICAL ANTIPSYCHOTICS ‐ short & medium‐term data, Outcome 9 Adverse effects: 2. General.
4.1
4.1. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 1 Leaving the study early.
4.2
4.2. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 2 Death.
4.3
4.3. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 3 Mental state: 1. Average change (PANSS, low score = good).
4.4
4.4. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 4 Mental state: 2. Average change in positive symptoms (PANSS positive subscale, low score = good)).
4.5
4.5. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 5 Mental state: 3. Average change in negative symptoms (PANSS negative subscale, low score = good).
4.6
4.6. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 6 Adverse effects: 1. Movement disorders.
4.7
4.7. Analysis
Comparison 4 QUETIAPINE (any dose) versus RISPERIDONE (any dose) ‐ all medium‐term data, Outcome 7 Adverse effects: 2. General.
See this image and copyright information in PMC

Update of

References

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Multi‐country 1999 {unpublished data only}
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North America 1996 {published data only}
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Faustman 1996 {published and unpublished data}
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Kufferle 1997 {published data only}
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Shimada 1994 {published data only (unpublished sought but not used)}
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Tauscher 1997 {published data only}
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Wetzel 1995 (005) {published data only}
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References to studies awaiting assessment

Germany 2002 {unpublished data only}
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Italy 2002 {unpublished data only}
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Japan 2002 {unpublished data only}
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    1. Nagao M, Mori K, Yamashita H, Yamawaki S. Switching to typical antipsychotics in chronic schizophrenic patients: prediction factors of efficacy. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S123.
Netherlands 2002 {unpublished data only}
    1. Bruggeman R, Knegtering H, Castelein S, Linde J, Bous J. Risperidone versus quetiapine: preliminary results of a comparative study on sexual dysfunctioning and prolactin elevation. Nordic Journal of Psychiatry 2002;56(2):14‐5.
Turkey 2001 {unpublished data only}
    1. Atmaca M, Kuloglu M, Tezcan E, Gecici O, Unal A, Firidin B. The comparison of quetiapine and haloperidol effects on serum prolactin in patients with schizophrenia. European Neuropsychopharmacology 2001;11(Suppl 3):S240.
USA 1999 {unpublished data only}
    1. Velligan DI. Neurocognitive advantages of quetiapine. Annual Meeting of the American Psychiatric Association, LA, USA. 2001.
    1. Velligan DI, Pultz J, Csernansky JG, Hoff AL, Mahurin R, Miller AL, Newcommer JW. Changes in cognitive function in quetiapine fumarate versus haloperidol. 1999 American Psychiatric Association Annual Meeting, Washington, DC, USA. 1999.
USA 2001 {unpublished data only}
    1. Lee M, Meltzer HY. Quetiapine is significantly superior to haloperidol and placebo in improving mood in patients with schizophrenia. 7th World Congress of Biological Psychiatry; 2001 Jul 1‐6; Berlin, Germany. 2001.

References to ongoing studies

UK 2003 {unpublished data only}
    1. Personal communication. Anonymous 2003.
USA 1998 {published data only}
    1. Hong WW, Rak IW, Ciuryla VT, Wilson AM, Kylstra JW, Meltzer HY, Carpenter Jr WT, Lehman A, Arvanitis LA. Medical‐claims databases in the design of a health‐outcomes comparison of quetiapine ('Seroquel') and usual‐care antipsychotic medication. Schizophrenia Research 1998;32:51‐8. - PubMed
USA 2000b {unpublished data only}
    1. Lieberman J, McEnvoy J, Stroup S. Protocol: comparative effectiveness of antipsychotic medications in patients with schizophrenia: revised in response to DSMB comments. National Institute of Mental Health 2000.
    1. Lieberman J, McEvoy J, Stroup S. Trial design summary: comparative effectiveness of antipsychotic medications in patients with schizophrenia: Draft. National Institute of Mental Health 2002.
    1. Lieberman JA, Schneider LS, McEvoy J, Pariot P, Stroup S, Adiao J, Lebowitz BD. Effectiveness trials of antipsychotic drugs. Annual Meeting of the American Psychiatry Association; 2001 May 5‐10; LA, USA.. 2001.

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