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

  • S. Leucht (a1), W. Kissling (a1) and J. M. Davis (a2)

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.

Corresponding author
*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:
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JM Davis , N Chen (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.

J Geddes , N Freemantle , P Harrison , P Bebbington (2000). Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. British Medical Journal 321, 13711376.

S Heres , J Davis , K Maino , E Jetzinger , W Kissling , S Leucht (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.

OJ Hoyberg , C Fensbo , J Remvig , O Lingjaerde , M Sloth-Nielsen , I Salvesen (1993). Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. Acta Psychiatrica Scandinavica 88, 395402.

PB Jones , TRE Barnes , L Davies , G Dunn , H Lloyd , KP Hayhurst , RM Murray , A Markwick , SW Lewis (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.

S Kasper , D Winkler (2006). Addressing the limitations of the CATIE study. World Journal of Biological Psychiatry 7, 126127.

S Leucht , C Corves , D Arbter , RR Engel , C Li , JM Davis (2009 a). Second-generation versus first-generation antipsychotics for schizophrenia: a meta-analysis. Lancet 373, 3141.

S Leucht , RR Engel , J Bauml , JM Davis (2007). Is the superior efficacy of new generation antipsychotics an artifact of LOCF? Schizophrenia Bulletin 33, 183191.

SW Lewis , TR Barnes , L Davies , RM Murray , G Dunn , KP Hayhurst , A Markwick , H Lloyd , PB Jones (2006). Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophrenia Bulletin 32, 715723.

JA Mattes (1997). Risperidone: how good is the evidence for efficacy? Schizophrenia Bulletin 23, 155161.

R Rosenheck , D Perlick , S Bingham , W Liu-Mares , J Collins , S Warren , D Leslie , E Allan , EC Campbell , S Caroff , J Corwin , L Davis , R Douyon , L Dunn , D Evans , E Frecska , J Grabowski , D Graeber , L Herz , K Kwon , W Lawson , F Mena , J Sheikh , D Smelson , V Smith-Gamble (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.

H Scherk , FG Pajonk , S Leucht (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.

N Schooler , J Rabinowitz , M Davidson , R Emsley , PD Harvey , L Kopala , PD McGorry , I Van Hove , M Eerdekens , W Swyzen , G De Smedt (2005). Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. American Journal of Psychiatry 162, 947953.

WO Tarnow-Mordi , MJ Healy (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.

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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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