Hostname: page-component-76fb5796d-25wd4 Total loading time: 0 Render date: 2024-04-26T11:59:00.364Z Has data issue: false hasContentIssue false
  • English
  • Français

Placebo controlled studies in acute schizophrenia – an issue of concern

Published online by Cambridge University Press:  16 April 2020

A Delini-Stula  and
D Berdah-Tordjman
A Delini-Stula
Affiliation:
Roche International Clinical Research Center, Parc Club des Tanneries, 4, Route de la Rivière, 67382Lingolsheim Cedex, France
D Berdah-Tordjman
Affiliation:
Roche International Clinical Research Center, Parc Club des Tanneries, 4, Route de la Rivière, 67382Lingolsheim Cedex, France
Get access

Summary

Placebo controlled studies in patients suffering from exacerbation eg acute productive episode of schizophrenia and performed in the period between 1963-1993 are reviewed and analysed with respect to study designs; size of studies; improvement rate under placebo and drop-outs due to inefficacy under placebo. The aim of the analysis was to find out if the reported data permit some realistic estimates for a priori assumptions needed for proper planning of such studies, particularly in view of the numerous ethical and other difficulties which their performance encounters in the practice. Literature research revealed a rather limited number of rigorous, placebo-controlled, monotherapy studies (without intermittent or concomitant additional neuroleptics) in acute schizophrenia. Across comparison of findings from these studies was difficult due to differences in duration of treatment, assessment instruments and criteria of efficacy which illustrated a lack of methodological standards for studies in this indication. The improvement rate under placebo, if measured by Clinical Global Assessment (CGI) appeared, however, not to exceed 25%, whereas BPRS score reduction as efficacy criterion mostly provided higher response rates (up to 40%). Of interest however, is the finding that the response rate to conventional neuroleptics at the end of 4-6 weeks of treatment in some studies hardly exceeded 40%. The most sensitive measure of placebo effect seemed to be the drop-out rate due to inefficacy (up to 100%) and it is suggested to consider this measure and the survival analysis approach in designing future studies. The review demonstrated many unresolved methodological problems in testing antipsychotic drugs in acute schizophrenia and, particularly, the need of scientific evidence of validity and sensitivity of measures of antipsychotic efficacy. The findings reported up to now do not offer cues for rational estimates of the effect size differences between placebo and active drugs after short-term treatment in acute schizophrenia.

Keywords

schizophreniaclinical trialsplacebo responseoutcome measuresneuroleptics
Type
Special article
Information
European Psychiatry , Volume 9 , Issue 4 , 1994 , pp. 165 - 173
Copyright
Copyright © European Psychiatric Association 1994

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

Ananth, JVVacaflor, LKekhwa, GSterlin, CBan, TANicotinic acid in the treatment of newly admitted schizophrenic patients: a placebocontrolled study4-5. Int J Clin Pharmacol 1972;5(4):406-10Google Scholar
Angst, JDie somatische Therapie der Schizophrenie. Stuttgart: G Thieme Verlag, 1969Google Scholar
Angst, JDinkelkamp, TDie somatische Therapie der Schizophrenie: Literatur der Jahre 1966-1972. Stuttgart: G Thieme Verlag, 1974Google Scholar
Angst, JHippius, HThird Consensus Conference: Methodology of Clinical Trials of Antipsychotic Drugs. Pharmacopsychiatr 1991;24(5):149-52CrossRefGoogle ScholarPubMed
McBain, SLDineen, MWeller, MTaylor, SCooksey, PWilliams, PCorn, TOndansetron, a double-blind placebo controlled study in acute schizophrenia. Schizophren Res 1992;6:112CrossRefGoogle Scholar
Bechelli, LPCRuffino-Netto, AHetem, GA double-blind controlled trial of pipotiazine, haloperidol and placebo in recently-hospitalized acute schizophrenic patients. Brazilian J Med Biol Res 1983; 16:305-11Google ScholarPubMed
Benkert, OMaier, WThe necessity of placebo application in psychotropic drug trials. Pharmacopsychiatr 1990;23:203-5CrossRefGoogle ScholarPubMed
Borison, RLSinha, DHaverstock, SMcLarnon, MCDiamond, BIEfficacy and safety of tiospirone vs haloperidol and thioridazine in a double-blind, placebo-controlled trial. Psychopharmacol Bull 1989;25 (2):190-3Google Scholar
Chouinard, GA placebo-controlled clinical trial of remoxipride and chlorpromazine in newly admitted schizophrenic patients with acute exacerbation. Acta Psychiatr Stand 1990;82 (358):111-9CrossRefGoogle Scholar
Chouinard, GJones, BRemington, GBloom, DAddington, DMacEwan, GWLabelle, ABeauclair, LArnott, W. ACanadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993;13 (1):25-40CrossRefGoogle ScholarPubMed
Clark, MLHuher, WKCharalampous, KDSerafetinides, EATrousdale, WColmore, JPDrug treatment in newly admitted schizophrenic patients. Arch Gen Psychiatr 1971;25:404-9CrossRefGoogle ScholarPubMed
Collins, EJHogan, TPNuttall, SEMethodological standards in schizophrenia research: a critical survey of clinical trials. Int J Methods Psychiatr Res 1992;2:111-6Google Scholar
Davis, JMCasper, RAntipsychotic drugs: clinical pharmacology and therapeutic use. Drugs 1977;14:260-82CrossRefGoogle ScholarPubMed
Goldberg, SCMattsson, NBSchizophrenic subtypes defined by response to drugs and placebo. Dis Nerv Syst 1968;29 (5):153-8Google ScholarPubMed
Hamill, WTFontana, AFThe immediate effects of chlorpromazine in newly admitted schizophrenic patients. Am J Psychiatr 1975; 132 (10):1023-6Google ScholarPubMed
Herrera, JCosta, JSramek, JHeh, CKhaled, DGutierrez, MAnanth, JThe efficacy of sustained-release thioridazine in the treatment of schizophrenic inpatients. Curr Ther Res 1990;48 (6):1006-11Google Scholar
Hekimian, LJFriedhoff, AJA controlled study of placebo, chlordiazepoxide and chlorpromazine with thirty male schizophrenic patients. Dis Nerv Syst 1967;28:675-78Google ScholarPubMed
Hirsch, SRBarnes, TRETesting of efficacy of new neuroleptic drugs. Psychopharmacol 1990;8:26–36Google ScholarPubMed
Johnston, ECCrow, TJFrith, CDCarney, MWPMechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet April 1978;22:848-51CrossRefGoogle Scholar
Klein, EBental, ELerer, BBelmaker, RHCarbamazepine and haloperidol vs placebo and haloperidol in excited psychoses. A controlled study. Arch Gen Psychiatr 1984;41:165-70CrossRefGoogle Scholar
Lewander, TWesterbergh, SEMorrison, DClinical profile of remoxipride – a combined analysis of a comparative double-blind multicentre trial programme. Acta Psychiatr Scand 1990;82 (358):92-8CrossRefGoogle Scholar
Lingjaerde, OBenzodiazepines in the treatment of schizophrenia: an updated survey. Acta Psychiatr Scand 1991;84:453-9CrossRefGoogle Scholar
Manchanda, RHirsch, SRDoes propanolol have an antipsychotic effect? A placebo-controlled study in acute schizophrenia. Br J Psychiatr 1986;148:701-7CrossRefGoogle ScholarPubMed
Möller, HJNeuroleptic treatment of negative symptoms in schizophrenic patients. Efficacy problems and methodological difficulties. Eur Neuropsychopharmacol 1993;3:1–11CrossRefGoogle ScholarPubMed
Montgomery, SAGreen, MRimon, Ret al. Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia. Acta Psychiatr Scand 1992;86:97–103CrossRefGoogle Scholar
Müller-Oerlinghausen, BNational and international guidelines for the conduct of clinical trials of psychotropic drugs. Pharmacopsychiatr 1990;8:167-74Google ScholarPubMed
National Institute of Mental Health Psychopharmacology Service Center Collaborative Study Group. Phenothiazine treatment in acute schizophrenia. Arch Gen Psychiatr 1964;10:246-61CrossRefGoogle Scholar
Price, WAAntipsychotic effects of verapamil in schizophrenia. Hillside J Clin Psychiatr 1987;9 (2):225-30Google Scholar
Prien, RFCarpenter, LLKupfer, DJThe definition and operational criteria for treatment outcome of major depressive disorder. Arch Gen Psychiatr 1991;48:796–800CrossRefGoogle ScholarPubMed
Reardon, JDAbrams, SAcute paranoid schizophrenia. Dis Nerv Syst 1966;27:265-70Google ScholarPubMed
Selman, FBMcClure, RFHelwig, HLoxapine succinate: a double-blind comparison with haloperidol and placebo in acute schizophrenics. Curr Ther Res 1976;19 (6):645-52Google ScholarPubMed
Shopsin, BKlein, HAaronsom, MCollora, MClozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients. Arch Gen Psychiatr 1979;36:657-64CrossRefGoogle ScholarPubMed
Stassen, HHDelini-Stula, AAngst, JTime course of improvement under antidepressant treatment: a survival-analytical approach. Eur J Neuropsychopharmacol 1993;3:127-35CrossRefGoogle ScholarPubMed
Wallace, KHThompson, RAImmunointervention in Man: a Critique of Clinical Trial Methodology. Oxford University Press, 1991Google Scholar
WHO – Guidelines. Review of Dependence Producing Psychoactive Substances for International Control. World Health Organization, 1985Google Scholar
Wolkowitz, OMPickar, DBenzodiazepines in the treatment of schizophrenia: a review and reappraisal. Am J Psychiatr 1991;148:714-26Google ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.