European Journal of Clinical Pharmacology

, Volume 70, Issue 2, pp 127–134 | Cite as

Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis

  • G. Désaméricq
  • F. Schurhoff
  • A. Meary
  • A. Szöke
  • I. Macquin-Mavier
  • A. C. Bachoud-Lévi
  • P. MaisonEmail author
Review Article



Most schizophrenic patients have mild to moderate cognitive impairment in the early stages of schizophrenia. The aim was to compare the long-term effects of various antipsychotic drugs on overall cognition and on specific cognitive domains in patients with schizophrenia or related disorders.


We searched MEDLINE and EMBASE for randomized controlled trials in which oral formulations of second-generation antipsychotic drugs were compared head-to-head or against placebo or against haloperidol. Trials had to be of at least 6 months duration to be included. We used a network meta-analysis to combine direct and indirect comparisons of the cognitive effects between antipsychotics.


Nine studies were eligible. The median trial duration was 52 weeks. Quetiapine, olanzapine and risperidone had better effects on global cognitive score than amisulpride (p < 0.05) and haloperidol (p < 0.05). When memory tasks were considered, ziprasidone had better effect than amisulpride (0.28 [0.02–0.54]) and haloperidol (0.32 [0.09–0.55]). Quetiapine was better than other drugs (p < 0.001) on attention and processing speed tasks, followed by ziprasidone (p < 0.05) and olanzapine (p < 0.05). The effects of quetiapine, risperidone and olanzapine were better than those of amisulpride (p < 0.05) on executive functions.


Our results suggest differences between antipsychotics in their effect on the overall cognitive score in schizophrenia. Quetiapine and olanzapine had the most positive effects, followed by risperidone, ziprasidone, amisulpride and haloperidol in that order. Significant differences were also observed according to specific cognitive tasks.


Schizophrenia Antipsychotic Neuropsychology Meta-analysis Cognition 



We thank Dr Manuel J. Cuesta, who kindly provided the data necessary for our analysis, and Ingrid Jamin and Eva Bulzacka, who helped to group the neurocognitive tests into cognitive domains.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2013_1600_MOESM1_ESM.doc (33 kb)
ESM 1 (DOC 33 kb)


  1. 1.
    Heinrichs RW, Zakzanis KK (1998) Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12:426–445PubMedCrossRefGoogle Scholar
  2. 2.
    Keefe RSE, Eesley CE, Poe MP (2005) Defining a cognitive function decrement in schizophrenia. Biol Psychiatry 57:688–691. doi: 10.1016/j.biopsych.2005.01.003 PubMedCrossRefGoogle Scholar
  3. 3.
    Bilder RM, Goldman RS, Robinson D et al (2000) Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 157:549–559PubMedCrossRefGoogle Scholar
  4. 4.
    Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330PubMedGoogle Scholar
  5. 5.
    Green MF, Kern RS, Braff DL, Mintz J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull 26:119–136PubMedCrossRefGoogle Scholar
  6. 6.
    Harvey PD, Howanitz E, Parrella M et al (1998) Symptoms, cognitive functioning, and adaptive skills in geriatric patients with lifelong schizophrenia: a comparison across treatment sites. Am J Psychiatry 155:1080–1086PubMedGoogle Scholar
  7. 7.
    Harvey PD, Green MF, Keefe RSE, Velligan DI (2004) Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry 65:361–372PubMedCrossRefGoogle Scholar
  8. 8.
    Hyman SE, Fenton WS (2003) Medicine. What are the right targets for psychopharmacology? Science 299:350–351. doi: 10.1126/science.1077141 PubMedCrossRefGoogle Scholar
  9. 9.
    Keefe RS, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222PubMedCrossRefGoogle Scholar
  10. 10.
    Mishara AL, Goldberg TE (2004) A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book. Biol Psychiatry 55:1013–1022. doi: 10.1016/j.biopsych.2004.01.027 PubMedCrossRefGoogle Scholar
  11. 11.
    Woodward ND, Purdon SE, Meltzer HY, Zald DH (2005) A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol 8:457–472. doi: 10.1017/S146114570500516X PubMedCrossRefGoogle Scholar
  12. 12.
    Thornton AE, Van Snellenberg JX, Sepehry AA, Honer W (2006) The impact of atypical antipsychotic medications on long-term memory dysfunction in schizophrenia spectrum disorder: a quantitative review. J Psychopharmacol (Oxford) 20:335–346. doi: 10.1177/0269881105057002 CrossRefGoogle Scholar
  13. 13.
    Davidson M, Galderisi S, Weiser M et al (2009) Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry 166:675–682. doi: 10.1176/appi.ajp.2008.08060806 PubMedCrossRefGoogle Scholar
  14. 14.
    Keefe RSE, Bilder RM, Davis SM et al (2007) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:633–647. doi: 10.1001/archpsyc.64.6.633 PubMedCrossRefGoogle Scholar
  15. 15.
    Keefe RSE, Sweeney JA, Gu H et al (2007) Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry 164:1061–1071. doi: 10.1176/appi.ajp.164.7.1061 PubMedCrossRefGoogle Scholar
  16. 16.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  17. 17.
    Lumley T (2002) Network meta-analysis for indirect treatment comparisons. Stat Med 21:2313–2324. doi: 10.1002/sim.1201 PubMedCrossRefGoogle Scholar
  18. 18.
    Guilera G, Pino O, Gómez-Benito J, Rojo JE (2009) Antipsychotic effects on cognition in schizophrenia: a meta-analysis of randomised controlled trials. Eur J Psychiatry 23:77–89. doi: 10.4321/S0213-61632009000200002 CrossRefGoogle Scholar
  19. 19.
    Keefe RSE, Seidman LJ, Christensen BK et al (2004) Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Am J Psychiatry 161:985–995PubMedCrossRefGoogle Scholar
  20. 20.
    Keefe RSE, Seidman LJ, Christensen BK et al (2006) Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biol Psychiatry 59:97–105. doi: 10.1016/j.biopsych.2005.06.022 PubMedCrossRefGoogle Scholar
  21. 21.
    Woodward ND, Purdon SE, Meltzer HY, Zald DH (2007) A meta-analysis of cognitive change with haloperidol in clinical trials of atypical antipsychotics: dose effects and comparison to practice effects. Schizophr Res 89:211–224. doi: 10.1016/j.schres.2006.08.021 PubMedCrossRefGoogle Scholar
  22. 22.
    Guo X, Zhai J, Wei Q et al (2011) Neurocognitive effects of first- and second-generation antipsychotic drugs in early-stage schizophrenia: a naturalistic 12-month follow-up study. Neurosci Lett 503:141–146. doi: 10.1016/j.neulet.2011.08.027 PubMedCrossRefGoogle Scholar
  23. 23.
    Andersen R, Fagerlund B, Rasmussen H et al (2011) Cognitive effects of six months of treatment with quetiapine in antipsychotic-naïve first-episode schizophrenia. Psychiatry Res 187:49–54. doi: 10.1016/j.psychres.2010.10.013 PubMedCrossRefGoogle Scholar
  24. 24.
    Basso MR, Bornstein RA, Lang JM (1999) Practice effects on commonly used measures of executive function across twelve months. Clin Neuropsychol 13:283–292. doi: 10.1076/clin. PubMedCrossRefGoogle Scholar
  25. 25.
    Szöke A, Trandafir A, Dupont M-E et al (2008) Longitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry 192:248–257. doi: 10.1192/bjp.bp.106.029009 PubMedCrossRefGoogle Scholar
  26. 26.
    Crespo-Facorro B, Rodríguez-Sánchez JM, Pérez-Iglesias R et al (2009) Neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode psychosis: a randomized, controlled 1-year follow-up comparison. J Clin Psychiatry 70:717–729. doi: 10.4088/JCP.08m04634 PubMedCrossRefGoogle Scholar
  27. 27.
    Baldwin D, Woods R, Lawson R, Taylor D (2011) Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ 342:d1199PubMedCrossRefGoogle Scholar
  28. 28.
    Riedel M, Schennach-Wolff R, Musil R et al (2010) Neurocognition and its influencing factors in the treatment of schizophrenia-effects of aripiprazole, olanzapine, quetiapine and risperidone. Hum Psychopharmacol 25:116–125. doi: 10.1002/hup.1101 PubMedCrossRefGoogle Scholar
  29. 29.
    Purdon SE, Jones BD, Stip E et al (2000) Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia. Arch Gen Psychiatry 57:249–258PubMedCrossRefGoogle Scholar
  30. 30.
    Purdon SE, Malla A, Labelle A, Lit W (2001) Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. J Psychiatry Neurosci 26:137–149PubMedCentralPubMedGoogle Scholar
  31. 31.
    Rosenheck R, Perlick D, Bingham S et al (2003) Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. JAMA 290:2693–2702. doi: 10.1001/jama.290.20.2693 PubMedCrossRefGoogle Scholar
  32. 32.
    Cuesta MJ, Jalón EG, Campos MS, Peralta V (2009) Cognitive effectiveness of olanzapine and risperidone in first-episode psychosis. Br J Psychiatry 194:439–445. doi: 10.1192/bjp.bp.108.055137 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • G. Désaméricq
    • 1
    • 2
    • 3
    • 4
  • F. Schurhoff
    • 2
    • 5
    • 6
  • A. Meary
    • 2
    • 5
    • 6
  • A. Szöke
    • 2
    • 5
    • 6
  • I. Macquin-Mavier
    • 2
    • 3
  • A. C. Bachoud-Lévi
    • 1
    • 2
    • 4
    • 7
  • P. Maison
    • 1
    • 2
    • 4
    • 7
    • 8
    Email author
  1. 1.Inserm, U955CréteilFrance
  2. 2.Université Paris Est, Faculté de MédecineCréteilFrance
  3. 3.AP-HP, Hôpital H. Mondor - A. Chenevier, Pharmacologie CliniqueCréteilFrance
  4. 4.Ecole Normale SupérieureDépartement d’Etudes CognitivesParisFrance
  5. 5.Inserm, U955CréteilFrance
  6. 6.AP-HP, Hôpital H. Mondor - A. Chenevier, Pôle de PsychiatrieCréteilFrance
  7. 7.AP-HP, Hôpital H. Mondor - A. Chenevier, Centre de Référence Maladie de HuntingtonCréteilFrance
  8. 8.IMRB - Inserm U955, Equipe 1, Neuropsychologie Interventionnelle, Faculté de Médecine de CréteilCréteilFrance

Personalised recommendations