Hostname: page-component-7c8c6479df-24hb2 Total loading time: 0 Render date: 2024-03-26T13:58:22.579Z Has data issue: false hasContentIssue false

Second-generation antipsychotics for schizophrenia: can we resolve the conflict?

Published online by Cambridge University Press:  01 April 2009

S. Leucht*
Affiliation:
Department of Psychiatry and Psychotherapy, Technische Universität München, Germany
W. Kissling
Affiliation:
Department of Psychiatry and Psychotherapy, Technische Universität München, Germany
J. M. Davis
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, USA
*
*Address for correspondence: S. Leucht, M.D., Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 München, Germany. (Email: Stefan.Leucht@Lrz.tu-muenchen.de)

Abstract

The initial enthusiasm about the second-generation or atypical antipsychotic drugs soon changed into criticism and debate, culminating in the controversial CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and EUFEST (European First-Episode Schizophrenia Trial) effectiveness trials. This review summarizes the results of three recent meta-analyses that compared second-generation antipsychotics (SGAs) with placebo, with conventional antipsychotics, and with SGAs head-to-head. We compare the meta-analyses with previous reviews and put them in the perspective of CATIE, CUtLASS and EUFEST. The data show that the SGAs are not a homogeneous group and that this confusing classification should be abandoned. We find that, overall, the data are consistent but experts interpret the same results differently. The debate seems to be driven more by values than by data; some place an emphasis on cost, others focus on extrapyramidal side-effects (EPS), weight gain, or efficacy. In our opinion, the SGAs are not the breakthrough that industry would like to maintain. They have different properties, so a clinician may individualize a treatment plan to a given patient's problems, a decision that should be shared with the patient. However, these drugs are important contributions to treatment, and most psychiatrists, let alone patients, would probably not want to do without them.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

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

Adams, CE, Coutinho, E, Davis, JM, Duggan, L, Li, C, Leucht, S, Tharyan, P, Cochrane Schizophrenia Group (2008). In The Cochrane Library. John Wiley & Sons Ltd: Chichester, UK.Google Scholar
Davis, JM, Chen, N (2001). The effects of olanzapine on the 5 dimensions of schizophrenia derived by factor analysis: combined results of the North American and international trials. Journal of Clinical Psychiatry 62, 757771.CrossRefGoogle ScholarPubMed
Davis, JM, Chen, N (2004). Dose–response and dose equivalence of antipsychotics. Journal of Clinical Psychopharmacology 24, 192208.CrossRefGoogle ScholarPubMed
Davis, JM, Chen, N, Glick, ID (2003). A meta-analysis of the efficacy of second-generation antipsychotics. Archives of General Psychiatry 60, 553564.CrossRefGoogle ScholarPubMed
Davis, JM, Chen, N, Glick, ID (2008). Issues that may determine the outcome of antipsychotic trials: industry sponsorship and extrapyramidal side effect. Neuropsychopharmacology 33, 971975.CrossRefGoogle ScholarPubMed
Findling, RA, Robb, A, Nyilas, M, Forbes, RA, Jin, N, Ivanova, S, Marcus, R, McQuade, RD, Iwamoto, T, Carson, WH (2008). A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. American Journal of Psychiatry 165, 14321441.Google Scholar
Geddes, J, Freemantle, N, Harrison, P, Bebbington, P (2000). Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. British Medical Journal 321, 13711376.CrossRefGoogle ScholarPubMed
Goode, E (2003). Leading drugs for psychosis come under new scrutiny. The New York Times, 20 May 2003.Google Scholar
Hamann, J, Leucht, S, Kissling, W (2003). Shared decision making in psychiatry. Acta Psychiatrica Scandinavica 107, 403409.Google Scholar
Heres, S, Davis, J, Maino, K, Jetzinger, E, Kissling, W, Leucht, S (2006). Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. American Journal of Psychiatry 163, 185194.CrossRefGoogle ScholarPubMed
Hoyberg, OJ, Fensbo, C, Remvig, J, Lingjaerde, O, Sloth-Nielsen, M, Salvesen, I (1993). Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. Acta Psychiatrica Scandinavica 88, 395402.CrossRefGoogle ScholarPubMed
Jones, PB, Barnes, TRE, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, Murray, RM, Markwick, A, Lewis, SW (2006). Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Archives of General Psychiatry 63, 10791086.CrossRefGoogle Scholar
Joy, CB, Adams, CE, Laurie, S (2007). Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews. Issue No. 4. Article No. CD003082.Google Scholar
Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe, Y, Keet, IPM, Gheorghe, MD, Rybakowski, JK, Galderisi, S, Libiger, J, Hummer, M, Dollfus, S, Lopez-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens, J, Lindefors, N, Riecher-Rossler, A, Grobbee, DE (2008). Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 10851097.CrossRefGoogle ScholarPubMed
Kane, JM, Honigfeld, G, Singer, J, Meltzer, H (1988). Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Archives of General Psychiatry 45, 789796.CrossRefGoogle ScholarPubMed
Kasper, S, Winkler, D (2006). Addressing the limitations of the CATIE study. World Journal of Biological Psychiatry 7, 126127.CrossRefGoogle ScholarPubMed
Kemmler, G, Hummer, M, Widschwendter, C, Fleischhacker, W (2005). Dropout rates in placebo-controlled and active-control clinical trials of antipsychotic drugs: a meta-analysis. Archives of General Psychiatry 62, 13051312.Google Scholar
Lehman, AF, Lieberman, JA, Dixon, LB, McGlashan, TH, Miller, AL, Perkins, DO, Kreyenbuhl, J, McIntyre, JS, Charles, SC, Altshuler, K, Cook, I, Cross, CD, Mellman, L, Moench, LA, Norquist, G, Twemlow, SW, Woods, S, Yager, J, Gray, SH, Askland, K, Pandya, R, Prasad, K, Johnston, R, Nininger, J, Peele, R, Anzia, DJ, Benson, RS, Lurie, L, Walker, RD, Kunkle, R, Simpson, A, Fochtmann, LJ, Hart, C, Regier, D (2004). Practice guideline for the treatment of patients with schizophrenia, second edition. American Journal of Psychiatry 161, 156.Google Scholar
Leucht, S, Arbter, D, Engel, RR, Kissling, W, Davis, JM (2008 a). How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Molecular Psychiatry. Published online: 8 January 2008. doi:10.1038/sj.mp.4002136.Google Scholar
Leucht, S, Corves, C, Arbter, D, Engel, RR, Li, C, Davis, JM (2009 a). Second-generation versus first-generation antipsychotics for schizophrenia: a meta-analysis. Lancet 373, 3141.CrossRefGoogle ScholarPubMed
Leucht, S, Engel, RR, Bauml, J, Davis, JM (2007). Is the superior efficacy of new generation antipsychotics an artifact of LOCF? Schizophrenia Bulletin 33, 183191.CrossRefGoogle ScholarPubMed
Leucht, S, Heres, S, Hamann, J, Kane, JM (2008 b). Methodological issues in current antipsychotic drug trials. Schizophrenia Bulletin 34, 275285.CrossRefGoogle ScholarPubMed
Leucht, S, Komossa, K, Rummel-Kluge, C, Corves, C, Hunger, H, Schmid, F, Asenjo Lobos, C, Schwarz, S, Davis, JM (2009 b). A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. American Journal of Psychiatry 166, 152163.Google Scholar
Lewis, SW, Barnes, TR, Davies, L, Murray, RM, Dunn, G, Hayhurst, KP, Markwick, A, Lloyd, H, Jones, PB (2006). Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophrenia Bulletin 32, 715723.CrossRefGoogle ScholarPubMed
Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, Keefe, RSE, Davis, SM, Davis, CE, Lebowitz, BD, Severe, J, Hsiao, JK (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 353, 12091223.Google Scholar
Marder, SR, Davis, JM, Chouinard, G (1997). The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. Journal of Clinical Psychiatry 58, 538546.CrossRefGoogle ScholarPubMed
Mattes, JA (1997). Risperidone: how good is the evidence for efficacy? Schizophrenia Bulletin 23, 155161.CrossRefGoogle ScholarPubMed
McEvoy, JP, Lieberman, JA, Stroup, TS, Davis, SM, Meltzer, HY, Rosenheck, RA, Swartz, MS, Perkins, DO, Keefe, RSE, Davis, CE, Severe, J, Hsiao, JK (2006). Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. American Journal of Psychiatry 163, 600610.Google Scholar
Olie, JP, Spina, E, Murray, S, Yang, R (2006). Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study. International Clinical Psychopharmacology 21, 143151.CrossRefGoogle ScholarPubMed
Rosenheck, R, Cramer, J, Xu, WC, Thomas, J, Henderson, W, Frisman, L, Fye, C, Charney, D (1997). A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. New England Journal of Medicine 337, 809815.CrossRefGoogle ScholarPubMed
Rosenheck, R, Perlick, D, Bingham, S, Liu-Mares, W, Collins, J, Warren, S, Leslie, D, Allan, E, Campbell, EC, Caroff, S, Corwin, J, Davis, L, Douyon, R, Dunn, L, Evans, D, Frecska, E, Grabowski, J, Graeber, D, Herz, L, Kwon, K, Lawson, W, Mena, F, Sheikh, J, Smelson, D, Smith-Gamble, V (2003). Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. Journal of the American Medical Association 290, 26932702.CrossRefGoogle ScholarPubMed
Rosenheck, RA (2005). Effectiveness versus efficacy of second-generation antipsychotics: haloperidol without anticholinergics as a comparator. Psychiatric Services 56, 8592.CrossRefGoogle ScholarPubMed
Scherk, H, Pajonk, FG, Leucht, S (2007). Second-generation antipsychotics in the treatment of acute mania: a systematic review and meta-analysis of randomized, controlled trials. Archives of General Psychiatry 64, 442455.CrossRefGoogle Scholar
Schooler, N, Rabinowitz, J, Davidson, M, Emsley, R, Harvey, PD, Kopala, L, McGorry, PD, Van Hove, I, Eerdekens, M, Swyzen, W, De Smedt, G (2005). Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. American Journal of Psychiatry 162, 947953.Google Scholar
Simpson, GM, Josiassen, RC, Stanilla, JK, De Leon, J, Nair, C, Abraham, G, Odom, WA, Turner, RM (1999). Double-blind study of clozapine dose response in chronic schizophrenia. American Journal of Psychiatry 156, 17441750.Google Scholar
Tarnow-Mordi, WO, Healy, MJ (1999). Distinguishing between ‘no evidence of effect’ and ‘evidence of no effect’ in randomised controlled trials and other comparisons. Archives of Disease in Childhood 80, 210211.Google Scholar
Zimbroff, DL, Kane, JM, Tamminga, CA, Daniel, DG, Mack, RJ, Wozniak, PJ, Sebree, TB, Wallin, BA, Kashkin, KB, Adan, F, Ainslie, G, Allan, E, Atri, P, Baker, R, Beitman, B, Brown, G, Canive, J, Carman, J, Dott, S, Edwards, J, Fenton, W, Freidli, J, Funderburg, L, Ereshefsky, L, Gladson, M, Hamilton, J, Haque, S, Hartford, J, Horne, R, Houck, C, Jampala, C, Labelle, A, Larson, G, Liesem, M, Liskow, B, Makela, E, Moore, N, Morphy, M, Posever, T, Risch, S, Rotrosen, J, Sheehan, D, Silverstone, P, Swann, A, Tapp, A, Thomas, M, Volavka, J, Vora, S (1997). Controlled, dose response study of sertindole and haloperidol in the treatment of schizophrenia. American Journal of Psychiatry 154, 782791.Google ScholarPubMed