Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 63
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Angermeyer, Matthias C. Van der Auwera, Sandra Matschinger, Herbert Carta, Mauro G. Baumeister, Sebastian E. and Schomerus, Georg 2016. The public debate on psychotropic medication and changes in attitudes 1990–2011. European Archives of Psychiatry and Clinical Neuroscience, Vol. 266, Issue. 2, p. 165.

    Gründer, Gerhard Heinze, Martin Cordes, Joachim Mühlbauer, Bernd Juckel, Georg Schulz, Constanze Rüther, Eckart and Timm, Jürgen 2016. Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study. The Lancet Psychiatry, Vol. 3, Issue. 8, p. 717.

    Leucht, Stefan Chaimani, Anna Cipriani, Andrea S. Davis, John M. Furukawa, Toshi A. and Salanti, Georgia 2016. Network meta-analyses should be the highest level of evidence in treatment guidelines. European Archives of Psychiatry and Clinical Neuroscience,

    Reutfors, Johan Clapham, Eric Bahmanyar, Shahram Brandt, Lena Jönsson, Erik G. Ekbom, Anders Bodén, Robert and Ösby, Urban 2016. Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study. Human Psychopharmacology: Clinical and Experimental, Vol. 31, Issue. 4, p. 341.

    Suzuki, Takefumi 2016. A further consideration on long-acting injectable versus oral antipsychotics in the treatment of schizophrenia: a narrative review and critical appraisal. Expert Opinion on Drug Delivery, Vol. 13, Issue. 2, p. 253.

    Anh, Nguyen Quynh Linh, Bui Ngoc Ha, Nguyen Thu Phanthunane, Pudtan and Huong, Nguyen Thanh 2015. Schizophrenia interventions in Vietnam: Primary results from a cost-effectiveness study. Global Public Health, Vol. 10, Issue. sup1, p. S21.

    Jiang, Yawen and Ni, Weiyi 2015. Health Care Utilization and Treatment Persistence Associated with Oral Paliperidone and Lurasidone in Schizophrenia Treatment. Journal of Managed Care & Specialty Pharmacy, Vol. 21, Issue. 9, p. 780.

    López-Muñoz, Francisco Sanz-Fuentenebro, Javier Rubio, Gabriel García-García, Pilar and Álamo, Cecilio 2015. Quo Vadis Clozapine? A Bibliometric Study of 45 Years of Research in International Context. International Journal of Molecular Sciences, Vol. 16, Issue. 9, p. 23012.

    Miyamoto, Seiya Merrill, David B. Fredrik Jarskog, L. Wolfgang Fleishhacker, W. Marder, Stephen R. and Lieberman, Jeffrey A. 2015. Psychiatry.

    Patel, M. X. Collins, S. Hellier, J. Bhatia, G. and Murray, R. M. 2015. The quality of reporting of phase II and III trials for new antipsychotics: a systematic review. Psychological Medicine, Vol. 45, Issue. 03, p. 467.

    Soeiro‑de‑Souza, M�rcio Dias, Vasco Missio, Giovanni Balanz�‑Martinez, Vicent Valiengo, Leandro Carvalho, Andr� and Moreno, Ricardo 2015. Role of quetiapine beyond its clinical efficacy in bipolar disorder: From neuroprotection to the treatment of psychiatric disorders (Review). Experimental and Therapeutic Medicine,

    Acosta, Francisco J. Chinea, Eugenio Hernández, José L. Rodríguez, Fernando García-Bello, Miguel Medina, Gema and Nieves, Wilson 2014. Influence of antipsychotic treatment type and regimen on the functionality of patients with schizophrenia. Nordic Journal of Psychiatry, Vol. 68, Issue. 3, p. 180.

    Bianchini, Oriana Porcelli, Stefano Nespeca, Claudia Cannavò, Dario Trappoli, Angela Aguglia, Eugenio De Ronchi, Diana and Serretti, Alessandro 2014. Effects of antipsychotic drugs on insight in schizophrenia. Psychiatry Research, Vol. 218, Issue. 1-2, p. 20.

    Guenette, Melanie Dawn Chintoh, Araba Remington, Gary and Hahn, Margaret 2014. Atypical Antipsychotic-Induced Metabolic Disturbances in the Elderly. Drugs & Aging, Vol. 31, Issue. 3, p. 159.

    McKenna, Peter J and Mortimer, Ann M 2014. Current and future treatment modalities in schizophrenia: novel antipsychotic drugs and cognitive therapy. Expert Review of Neurotherapeutics, Vol. 14, Issue. 1, p. 67.

    Möller, H.-J. Seemüller, F. Schennach-Wolff, R. Stübner, S. Rüther, E. and Grohmann, R. 2014. History, background, concepts and current use of comedication and polypharmacy in psychiatry. The International Journal of Neuropsychopharmacology, Vol. 17, Issue. 07, p. 983.

    Suzuki, Takefumi Uchida, Hiroyuki Takeuchi, Hiroyoshi Tsuboi, Takashi Hirano, Jinichi and Mimura, Masaru 2014. A review on schizophrenia and relapse-a quest for user-friendly psychopharmacotherapy. Human Psychopharmacology: Clinical and Experimental, Vol. 29, Issue. 5, p. 414.

    Wilson, Christina A. and Koenig, James I. 2014. Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia. European Neuropsychopharmacology, Vol. 24, Issue. 5, p. 759.

    Fusar-Poli, P. Smieskova, R. Kempton, M.J. Ho, B.C. Andreasen, N.C. and Borgwardt, S. 2013. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neuroscience & Biobehavioral Reviews, Vol. 37, Issue. 8, p. 1680.

    Guenette, Melanie D. Hahn, Margaret Cohn, Tony A. Teo, Celine and Remington, Gary J. 2013. Atypical antipsychotics and diabetic ketoacidosis: a review. Psychopharmacology, Vol. 226, Issue. 1, p. 1.


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

  • S. Leucht (a1), W. Kissling (a1) and J. M. Davis (a2)
  • DOI:
  • Published online: 01 April 2009

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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

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.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *