Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-23T03:12:42.242Z Has data issue: false hasContentIssue false
  • English
  • Français

Meta-analysis of drop-out rates in randomised clinical trials, comparing typical and atypical antipsychotics in the treatment of schizophrenia

Submitted to European Psychiatry. A poster of this work was presented at the WPA International Congress in Florence (November 10–13, 2004). Poster session PO1: Psychotic Disorders

Published online by Cambridge University Press:  16 April 2020

José Luis R. Martin ,
Víctor Pérez ,
Montse Sacristán ,
Fernando Rodríguez-Artalejo ,
Cristóbal Martínez  and
Enric Álvarez
José Luis R. Martin*
Affiliation:
Department of Clinical Research, Castilla-La Mancha Health Research Foundation (FISCAM), Edificio Bulevar, C/Berna, No. 2, Local 0-2, 45003 Toledo, Castilla-La Mancha, Spain University of Castilla-La Mancha, Toledo, Spain
Víctor Pérez
Affiliation:
Department of Psychiatry, Santa Creu and Sant Pau Hospital, Barcelona, Spain
Montse Sacristán
Affiliation:
Department of Clinical Research, Castilla-La Mancha Health Research Foundation (FISCAM), Edificio Bulevar, C/Berna, No. 2, Local 0-2, 45003 Toledo, Castilla-La Mancha, Spain
Fernando Rodríguez-Artalejo
Affiliation:
Department of Preventive Medicine and Public Health, Autonomous University of Madrid, Madrid, Spain
Cristóbal Martínez
Affiliation:
Department of Clinical Pharmacology, Alarcos Hospital, Ciudad Real, Spain
Enric Álvarez
Affiliation:
Department of Psychiatry, Santa Creu and Sant Pau Hospital, Barcelona, Spain
*
*Corresponding author. Tel.: +34 92 528 1144; fax: +34 92 528 1149. E-mail address:[email protected] (J.L.R. Martin).
Get access

Abstract

Objective

To assess antipsychotic medication in the treatment of schizophrenia, based on trial drop-out rates.

Methods

The studies included were randomised controlled trials that compared any of the four clinically best-established atypical antipsychotics (quetiapine, olanzapine, risperidone or clozapine) against either of two typical antipsychotics regarded as the gold standard (haloperidol or chlorpromazine).

Results

Meta-analysis indicated less risk of all-cause patient withdrawal from atypical medication trials where dosage was flexible, in both the short, relative risk (RR) 0.70 (95% CI 0.64–0.76), P < 0.00001, and long term, RR 0.72 (0.65–0.80), P < 0.00001. Similar results were observed for withdrawal due to adverse events, RR: 0.54 (0.41–0.72), P < 0.0001. Nevertheless, the favourable effects of atypical medication disappeared in trials relying on fixed dosage.

Conclusions

We detected a significant positive effect in terms of the outcome of treatment discontinuation for atypical versus typical medication, though only where the use of flexible rather than fixed doses (closer to an experimental control situation) was possible.

Keywords

Systematic reviewMeta-analysisSchizophreniaClinical trials
Type
Review
Information
European Psychiatry , Volume 21 , Issue 1 , January 2006 , pp. 11 - 20
Copyright
Copyright © Elsevier SAS 2006

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.)

References

Daumit, GLCrum, RMGuallar, EPowe, NRPrimm, ABSteinwachs, DMet al.Outpatients prescriptions for atypical antipsychotics for African Americans, Hispanics, and Whites in the United States. Arch. Gen. Psychiatry 2003;60:121–128.CrossRefGoogle Scholar
Lieberman, JAAtypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. J. Clin. Psychiat. 1996;57(11):68–71.Google ScholarPubMed
Sarif, ZACommon treatment goals of antipsychotics: acute treatment. J. Clin. Psychiat. 1998;59(19):5–8.Google Scholar
Kay, SRFiszbein, AThe positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 1987;13:261–275.CrossRefGoogle Scholar
Chouinard, GJones, BRemington, GBlooom, DAddington, DMacEwan, GWet al.A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J. Clin. Psychopharm. 1993;13:25–40.CrossRefGoogle ScholarPubMed
Hamilton, SHRevicki, DAGenduso, LABeasley, CMOlanzapine versus placebo and haloperidol: quality of life and efficacy results of the North American Double-blind trial. Neuropsychopharmacol 1998;18:41–49.CrossRefGoogle ScholarPubMed
Purdon, SEJones, BStip, ELabelle, AAddington, DDavid, SRet al.Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. Canadian Collaborative Group for Research on cognition in schizophrenia. Arch. Gen. Psychiatry 2000;57:249–258.CrossRefGoogle ScholarPubMed
Khan, AKhan, SRWalens, GKolts, RGiller, ELFrequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the food and drug administration summary basis of approval reports. Neuropsychopharmacol 2003;28:552–557.CrossRefGoogle ScholarPubMed
Hotopf, MChurchill, RLewis, GPragmatic randomised controlled trials in psychiatry. Br. J. Psychiat. 1999;175:217–223.CrossRefGoogle Scholar
Frackiewicz, EJSramek, JJHerrera, JMKurtz, NMCutler, NREthnicity and antipsychotic response. Ann. Pharmacother. 1997;31:1360–1369.CrossRefGoogle ScholarPubMed
Colton, TStatistics in medicine. Boston: Little, Brown and Company; 1974.Google Scholar
Deeks, JJAltman, DGEffect measures for meta-analysis of trials with binary outcomes. In: Egger, MDavey Smith, GAltman, DG, editors. Systematic reviews in health care: meta-analysis in context (. London: BMJ Publication Group; 2001.Google Scholar
Higgins, JPTThompson, SGDeeks, JJAltman, DGMeasuring inconsistency in meta-analysis. BMJ 2003;327:557–560.CrossRefGoogle Scholar
Buchanan, RWBreier, AKirkpatrick, BBall, PCarpenter, WTPositive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am. J. Psychiat. 1998;155:751–760.Google ScholarPubMed
Kane, JMMarder, SRSchooler, NRWirshing, WCUmbricht, DBaker, RWet al.Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Arch. Gen. Psychiatry 2001;58:965–972.CrossRefGoogle ScholarPubMed
Rosenheck, RCramer, JXu, WThomas, JHenderson, WFrisman, Let al.A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N. Engl. J. Med. 1997;337:809–815.CrossRefGoogle ScholarPubMed
Guirguis, EVoineskos, GGray, JSchierman, EClozapine (Leponex) vs. Chlorpromaxine (Largactil) in acute schizophrenia (a double-blind controlled study). Curr. Ther. Res. 1977;21:707–719.Google Scholar
Kane, JHonigfeld, GSinger, JMeltzer, HClozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch. Gen. Psychiatry 1988;45:789–796.CrossRefGoogle ScholarPubMed
León, CATherapeutic effect of clozapine. A 4-year follow up of a controlled clinical trial. Acta Psychiatr. Scand. 1979;59:471–480.CrossRefGoogle ScholarPubMed
Arvanitis, LAMiller, BGSeroquel Trial 13 Study Group. Multiple fixed doses of ‘Seroquel’ (Quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol. Psychiat. 1997;42:233–246.CrossRefGoogle Scholar
Copolov, DLLink, CGGKowalcyk, BA multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636 ‘Seroquel’) and haloperidol in schizophrenia. Psychol. Med. 2000;30:95–105.CrossRefGoogle Scholar
Emsley, RARaniwalla, JBailey, PJJones, AMA comparison of the effects of quetiapine (‘Seroquel’) and haloperidol in schizophrenia patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. Int. Clin. Psychopharm. 2000;15:121–131.CrossRefGoogle Scholar
Peuskens, JLink, CGGA comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr. Scand. 1997;96:265–273.CrossRefGoogle ScholarPubMed
Beasley, CMTollefson, GTran, PSatterlee, WSanger, THamilton, SOlanzapine versus placebo and haloperidol. Acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacol 1996;14:11–123.Google ScholarPubMed
Beasley, CM Jr.Hamilton, SHCrawford, AMDellva, Ma.Tollefson, GDTran, PVet al.Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Eur. Neuropsychopharm. 1997;7:125–137.CrossRefGoogle ScholarPubMed
Hamilton, SHEdgell, ETRevicki, DABreier, AFunctional outcome in schizophrenia: a comparison of olanzapine and haloperidol in a European sample. Int. Clin. Psychopharm. 2000;15:245–255.CrossRefGoogle Scholar
Lieberman, JATollefson, GTohen, MGreen, AIGur, REKahn, Ret al.Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am. J. Psychiat. 2003;160:1396–1404.CrossRefGoogle ScholarPubMed
Tollefson, GDBeasley, CM Jr.Tran, PVStreet, Js.Krueger, JATamura, RNet al.Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am. J. Psychiat. 1997;154:457–465.Google ScholarPubMed
Conley, RRTamminga, CABartko, JJRichardson, CPeszke, MLingle, Jet al.Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia. Am. J. Psychiat. 1998;155:914–920.CrossRefGoogle ScholarPubMed
Ceskova, ESvestka, JDouble-blind comparison of risperidone and haloperidol in schizophrenic and schizoaffective psychoses. Pharmacopsychiatry 1993;26:121–124.CrossRefGoogle ScholarPubMed
Claus, ABollen, JDe Cuyper, HEneman, MMalfroid, MPeuskens, Jet al.Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. Acta Psychiatr. Scand. 1992;85:295–305.CrossRefGoogle ScholarPubMed
Csernansky, JGMahmoud, RBrenner, RA comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N. Engl. J. Med. 2002;346:16–22.CrossRefGoogle ScholarPubMed
Emsley, RARisperidone Working Group. Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Schizophr. Bull. 1999;25:721–729.CrossRefGoogle Scholar
Heck, AHHaffmans, PMGroot, IWHoencamp, ERisperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial. Schizophr. Res. 2000;46:97–105.CrossRefGoogle ScholarPubMed
Marder, SRMeibach, RCRisperidone in the treatment of schizophrenia. Am. J. Psychiat. 1994;151:825–835.Google ScholarPubMed
Peuskens, JRisperidone Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Brit. J. Psychiat. 1995;166:712–726.CrossRefGoogle Scholar
Wirshing, DAMarshall, BD Jr.Green, MFMintz, JMarder, SRWirshing, WCRisperidone in treatment-refractory schizophrenia. Am. J. Psychiat. 1999;156:1374–1379.Google ScholarPubMed
Volavka, JCzobor, PSheitman, BLindenmayer, JPCitrome, LMcEvoy, JPet al.Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am. J. Psychiat. 2002;159:255–262.CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV). Washington: DC: APA; 1994.Google Scholar
Moher, DSchulz, KFAltman, DGThe CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:1191–1194.CrossRefGoogle Scholar
Review Manager (RevMan) [Computer program]. Version 4.2 for Windows. Oxford, England: The Cochrane Collaboration, 2003.Google Scholar
Borenstein, M.Rothstein, H. Comprehensive Meta-AnalysisTM. Biostat®; 1999. http://www.MetaAnalysis.com.Google Scholar
Leucht, SBarnes, TRKissling, WEngel, RRCorrell, CKane, JMRelapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials. Am. J. Psychiat. 2003;160:1209–1222.CrossRefGoogle ScholarPubMed
Leucht, SWahlbeck, KHamann, JKissling, WNew generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 2003;361:1581–1589.CrossRefGoogle ScholarPubMed
Gilbory, SMBagnall, AMDuggan, LTuunainen, ARisperidone versus other atypical antipsychotic medication for schizophrenia (Cochrane Review). The Cochrane library, issue 1 Chichester, UK: John Wiley & Sons, Ltd; 2004.Google Scholar
Duggan, LFenton, MDardennes, RMEl-Dosoky, AIndran, SOlanzapine for schizophrenia (Cochrane Review). The Cochrane library, issue 1 Chichester, UK: John Wiley & Sons, Ltd; 2004.Google Scholar
Srisurapanont, MDisayavanish, CTaimkaew, KQuetiapine for schizophrenia (Cochrane Review). The Cochrane library, issue 1 Chichester, UK: John Wiley & Sons, Ltd; 2004.Google Scholar
Lieberman, J.McEvoy, J.Stroup, S. Clinical antipsychotic trials in intervention effectiveness (CATIE). Comparative effectiveness of antipsychotic medications in patients with schizophrenia. http://www.catie.unc.edu/schizophrenia/synopsis.html.Google Scholar
Davis, JMChen, NGlick, IDA meta-analysis of the efficacy of second-generation antipsychotics. Arch. Gen. Psychiatry 2003;60:553–564.CrossRefGoogle ScholarPubMed
Geddes, JFreemantle, NHarrison, PBebbington, PAtypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ 2000;321:1371–1376.CrossRefGoogle ScholarPubMed
Martin, JLRPérez, VSacristán, MAlvarez, EIs grey literature essential for a better control of publication bias in psychiatry? An example from three meta-analysis of schizophrenia. Eur. Psychiatry 2005 (In press).CrossRefGoogle ScholarPubMed
Rummel, CHamann, JKissling, Leucht, SNew generation antipsychotics for first episode schizophrenia (Cochrane Review). The Cochrane library, issue 1 Chichester, UK: John Wiley & Sons, Ltd; 2004.Google Scholar
Gilbody, SWahlbeck, KAdams, CRandomized controlled trials in schizophrenia: a critical perspective on the literature. Acta Psychiatr. Scand. 2002;105:243–251.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.