Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-25T17:28:12.143Z Has data issue: false hasContentIssue false
  • English
  • Français

Efficacy of olanzapine in comparison with clozapine for treatment-resistant schizophrenia: evidence from a systematic review and meta-analyses

Published online by Cambridge University Press:  20 December 2012

Juliano S Souza ,
Monica Kayo ,
Ivson Tassell ,
Camila Bertini Martins  and
Helio Elkis
Juliano S Souza*
Affiliation:
Schizophrenia Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
Monica Kayo
Affiliation:
Schizophrenia Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
Ivson Tassell
Affiliation:
Schizophrenia Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
Camila Bertini Martins
Affiliation:
Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil
Helio Elkis
Affiliation:
Schizophrenia Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
*
*Address for correspondence: Juliano Santos Souza, University of São Paulo Medical School, Projesq–Schizophrenia Program, Rua Ovidio Pires de Campos 785, São Paulo SP-05403-010, Brazil. Email Juliano.s.souza@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction

Clozapine is considered the gold standard for the treatment of patients with treatment-resistant schizophrenia (TRS); however, randomized controlled trials (RCT) of olanzapine showed efficacy similar to clozapine in patients with TRS.

Methods

A systematic review was conducted comparing clozapine with olanzapine in patients with TRS. Meta-analyses were performed for single outcome measures. Response to treatment was measured by the percentage of responders, or mean change or endpoint values of psychotic symptoms scales. Effect sizes were shown as relative risks (RR), or standardized mean differences, with 95% confidence intervals.

Findings

Seven RCT were included, comprising 648 patients. Five meta-analyses were performed. Olanzapine and clozapine had similar effects on dropout rates (RR = 0.93, CI95% = 0.77–1.12), PANSS total endpoints (SMD = 0.21, CI95% = –0.04–0.46), and PANSS total mean changes (SMD = 0.08, CI95% = –0.01–0.027). Clozapine was superior to olanzapine for PANSS positive (SMD = 0.51, CI95% = 0.17–0.86) and negative (SMD = 0.50, CI95% = 0.16–0.85) subscales. There was a trend toward high doses of olanzapine producing higher effect sizes for this drug.

Conclusions

The results of this study suggest that clozapine is significantly more efficacious than olanzapine in improving positive and negative symptoms in TRS patients.

Keywords

clozapineolanzapinetreatment-resistant schizophreniameta-analysissystematic reviewschizophrenia
Type
Original Research
Information
CNS Spectrums , Volume 18 , Issue 2 , April 2013 , pp. 82 - 89
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

The authors would like to thank Dr. Carlos B. Pereira, Dr. Ricardo Moreno, and Dr. Orestes Forlenza for their valuable critical comments and suggestions for the manuscript, and also Carolina Rehem, for her library assistance.

References

1.Mueser, KT, McGurk, SR. Schizophrenia. Lancet. 2004; 363(9426): 2063–2072.CrossRefGoogle ScholarPubMed
2.Meltzer, H, Kostakoglu, A. Treatment resistant schizophrenia. In: Liberman J, Murray R, eds. Comprehensive Care of Schizophrenia: A Textbook of Clinical Management. London: Martin Dunitz; 2001: 181–203.Google Scholar
3.Elkis, H. Treatment-resistant schizophrenia. Psychiatr Clin North Am. 2007; 30(3): 511–533.CrossRefGoogle ScholarPubMed
4.McEvoy, J. The cost of schizophrenia. J Clin. Psychiatry. 2007; 68(suppl 14): 4–7.Google Scholar
5.Elkis, H, Meltzer, HY. [Refractory schizophrenia]. Rev Bras Psiquiatr. 2007; 29(Suppl 2): S41–S47.CrossRefGoogle ScholarPubMed
6.Brambilla, P, Barale, F, Caverzasi, F, Tognoni, G, Barbui, C. Clozapine-treated subjects with treatment-resistant schizophrenia: a systematic review of experimental and observational studies. Int. Clin. Psychopharmcol. 2002; 17: 189–195.CrossRefGoogle ScholarPubMed
7.Chakos, M, Lieberman, J, Hoffman, E, Bradford, D, Sheitman, B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 2001; 158: 518–526.CrossRefGoogle ScholarPubMed
8.Davis, JM, Chen, N, Glick, ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry. 2003; 60(6): 553–564.CrossRefGoogle ScholarPubMed
9.Essali, A, Al-Haj, H, Li, C, Rathbone, J. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2009: CD000059.Google ScholarPubMed
10.Leucht, S, Corves, C, Arbter, D, etal. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009; 373(9657): 31–41.CrossRefGoogle ScholarPubMed
11.Moncrieff, J. Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. Br J Psychiatry. 2003; 183: 161–166.CrossRefGoogle ScholarPubMed
12.Wahlbeck, K, Cheine, M, Essali, A, Adams, C. Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry. 1999; 156(7): 990–999.CrossRefGoogle ScholarPubMed
13.Sernyak, MJ, Rosenheck, RA. Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006. Psychiatr Serv. 2008; 59(5): 567–569.CrossRefGoogle ScholarPubMed
14.Leucht, S, Kissling, W, Davis, JM. Second-generation antipsychotics for schizophrenia: can we resolve the conflict? Psychol Med. 2009; 39(10): 1591–1602.CrossRefGoogle ScholarPubMed
15.Buchanan, RW, Kreyenbuhl, J, Kelly, DL, Noel, JM, Boggs, DL, Fischer, BA, etal. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010; 36(1): 71–93.CrossRefGoogle ScholarPubMed
16.Bondolfi, G, Dufour, H, Patris, M, etal. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. the Risperidone Study Group. Am J Psychiatry. 1998; 155: 499–504.CrossRefGoogle ScholarPubMed
17.Breier, A, Malhotra, A, Su, T, etal. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. Am J Psychiatry. 1999; 156: 294–298.CrossRefGoogle ScholarPubMed
18.Asenjo Lobos, C, Komossa, K, Rummel-Kluge, C, etal. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010; (11): CD006633.Google ScholarPubMed
19.Leucht, S, Komossa, K, Rummel-Kluge, C, etal. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009; 166(2): 152–163.CrossRefGoogle ScholarPubMed
20.Lewis, S, Barnes, T, Davies, L, etal. Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull. 2006; 32: 715–723.CrossRefGoogle ScholarPubMed
21.McEvoy, J, Lieberman, J, Stroup, T, etal. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006; 163: 600–610.CrossRefGoogle Scholar
22.Johnsen, E, Jorgensen, HA. Effectiveness of second generation antipsychotics: a systematic review of randomized trials. BMC Psychiatry. 2008; 8: 31–45.Google ScholarPubMed
23.Davis, JM, Chen, N. Dose response and dose equivalence of antipsychotics. J Clin Psychopharmacol. 2004; 24(2): 192–208.CrossRefGoogle ScholarPubMed
24.Simpson, GM, Josiassen, RC, Stanilla, JK, etal. Double-blind study of clozapine dose response in chronic schizophrenia. Am J Psychiatry. 1999; 156(11): 1744–1750.CrossRefGoogle ScholarPubMed
25.Meltzer, H, Bobo, W, Roy, A, etal. A randomized, double-blind comparison of clozapine and high-dose olanzapine in treatment-resistant patients with schizophrenia. J Clin Psychiatry. 2008; 69(2): 274–285.CrossRefGoogle ScholarPubMed
26.Citrome, L, Stauffer, VL, Chen, L, etal. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009; 29(3): 278–283.CrossRefGoogle Scholar
27.Kinon, BJ, Volavka, J, Stauffer, V, etal. Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study. J Clin Psychopharmacol. 2008; 28(4): 392–400.CrossRefGoogle ScholarPubMed
28.Citrome, L, Holt, RI, Walker, DJ, Hoffmann, VP. Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder. Clin Drug Investig. 2011; 31(7): 455–482.CrossRefGoogle ScholarPubMed
29.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed.Washington, DC: American Psychiatric Press; 1994.Google Scholar
30.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2): 261–276.CrossRefGoogle ScholarPubMed
31.Overall, J, Gorham, D. The Brief Psychiatric Rating Scale. Psychol Rep. 1962; 10: 799–812.CrossRefGoogle Scholar
32.Guy, W. Clinical Global Impression: ECDEU Assessment Manual for Psychopharmacology, Rev. ed.Rockville, MD: National Institutes of Mental Health; 1976: 218–222.Google Scholar
33.Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Intervention. London: The Cochrane Collaboration; 2009.Google Scholar
34.Comprehensive Meta-Analysis. Englewood, NJ: Biostat. Available at http://www.meta-analysis.com. Accessed August 2009.Google Scholar
35.Egger, M, Smith, GD, Altman, DG, Eds. Systematic Reviews in Health Care. Meta-Analysis in Context. London: BMJ Books; 2001.CrossRefGoogle Scholar
36.Atkins, M, Burgess, A, Bottomley, C, Riccio, M. Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. The Psychiatrist. 1997; 21: 224–226.Google Scholar
37.Woods, SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry. 2003; 64(6): 663–667.CrossRefGoogle ScholarPubMed
38.Azorin, J, Spiegel, R, Remington, G, etal. A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Am J Psychiatry. 2001; 158: 1305–1313.CrossRefGoogle ScholarPubMed
39.Bitter, I, Dossenbach, M, Brook, S, etal. Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003; 28: 173–180.CrossRefGoogle Scholar
40.Conley, RR, Kelly, DL, Richardson, CM, Tamminga, CA, Carpenter, WT Jr. The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: a double-blind, crossover study. J Clin Psychopharmacol. 2003; 23(6): 668–671.CrossRefGoogle ScholarPubMed
41.Moresco, R, Cavallaro, R, Messa, C, etal. Cerebral D2 and 5-HT2 receptor occupancy in schizophrenic patients treated with olanzapine or clozapine. J Psychopharmacol. 2004; 18(3): 355–365.CrossRefGoogle ScholarPubMed
42.Naber, D, Riedel, M, Klimke, A, etal. Randomized double blind comparison of olanzapine vs. clozapine on subjective wellbeing and clinical outcome in patients with schizophrenia. Acta Psychiatr Scand. 2005; 111: 106–115.CrossRefGoogle ScholarPubMed
43.Sacchetti, E, Galluzzo, A, Valsecchi, P, etal. Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study. Schizophr Res. 2009; 110(1–3): 80–89.CrossRefGoogle ScholarPubMed
44.Tollefson, G, Birkett, M, Kiesler, G, Wood, A. Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. Biol Psychiatry. 2001; 49: 52–63.CrossRefGoogle ScholarPubMed
45.Volavka, J, Czobor, P, Sheitman, B. Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry. 2002; 159: 255–262.CrossRefGoogle ScholarPubMed
46.Fanous, A, Lindenmayer, J. Schizophrenia and schizoaffective disorder treated with high doses of olanzapine. J Clin Psychopharmacol. 1999; 19: 275–276.CrossRefGoogle ScholarPubMed
47.Kumra, S, Kranzler, H, Gerbino-Rosen, G, etal. Clozapine versus “high-dose” olanzapine in refractory early-onset schizophrenia: an open-label extension study. J Child Adolesc Psychopharmacol. 2008; 18(4): 307–316.CrossRefGoogle ScholarPubMed
48.Kumra, S, Kranzler, H, Gerbino-Rosen, G, etal. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry. 2008; 63: 524–529.CrossRefGoogle ScholarPubMed
49.Launer, M. Place of olanzapine in therapy. Pharmaceut J. 1998: 260–267.Google Scholar
50.Lindenmayer, J, Volavka, J, Lieberman, J, etal. Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial. J Clin Psychopharmacol. 2001; 21(4): 448–453.CrossRefGoogle ScholarPubMed
51.Mountjoy, C, Baldacchino, A, Stubbs, J. British experience with high-dose olanzapine for treatment-refractory schizophrenia. Am J Psychiatry. 1999; 156: 158–159.CrossRefGoogle ScholarPubMed
52.Reich, J. Use of high-dose olanzapine in refractory psychosis. Am J Psychiatry. 1999; 156: 661.CrossRefGoogle ScholarPubMed
53.Sheitman, B, Lindgren, J, Early, J, Sved, M. High-dose olanzapine for treatment-refractory schizophrenia. Am J Psychiatry. 1997; 154(11): 1626 (letter).CrossRefGoogle ScholarPubMed
54.Kelly, DL, Richardson, CM, Yu, Y, Conley, RR. Plasma concentrations of high-dose olanzapine in a double-blind crossover study. Hum Psychopharmacol. 2006; 21(6): 393–398.CrossRefGoogle Scholar
55.Perry, PJ, Argo, TR, Carnahan, RM, etal. The association of weight gain and olanzapine plasma concentrations. J Clin Psychopharmacol. 2005; 25(3): 250–254.CrossRefGoogle ScholarPubMed