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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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References

  1. Heinrichs RW, Zakzanis KK (1998) Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12:426–445

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  3. Bilder RM, Goldman RS, Robinson D et al (2000) Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 157:549–559

    Article  CAS  PubMed  Google Scholar 

  4. Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330

    CAS  PubMed  Google Scholar 

  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 26:119–136

    Article  CAS  PubMed  Google Scholar 

  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 155:1080–1086

    CAS  PubMed  Google Scholar 

  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 65:361–372

    Article  PubMed  Google Scholar 

  8. Hyman SE, Fenton WS (2003) Medicine. What are the right targets for psychopharmacology? Science 299:350–351. doi:10.1126/science.1077141

    Article  CAS  PubMed  Google Scholar 

  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 25:201–222

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  Google Scholar 

  17. Lumley T (2002) Network meta-analysis for indirect treatment comparisons. Stat Med 21:2313–2324. doi:10.1002/sim.1201

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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 161:985–995

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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.13.3.283.1743

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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:d1199

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 57:249–258

    Article  CAS  PubMed  Google Scholar 

  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 26:137–149

    CAS  PubMed Central  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Inserm, U955, Equipe 01, Créteil, 94000, France

    G. Désaméricq, A. C. Bachoud-Lévi & P. Maison

  2. Université Paris Est, Faculté de Médecine, Créteil, 94000, France

    G. Désaméricq, F. Schurhoff, A. Meary, A. Szöke, I. Macquin-Mavier, A. C. Bachoud-Lévi & P. Maison

  3. AP-HP, Hôpital H. Mondor - A. Chenevier, Pharmacologie Clinique, Créteil, 94000, France

    G. Désaméricq & I. Macquin-Mavier

  4. Ecole Normale Supérieure, Département d’Etudes Cognitives, Paris, 75005, France

    G. Désaméricq, A. C. Bachoud-Lévi & P. Maison

  5. Inserm, U955, Equipe 15, Créteil, 94000, France

    F. Schurhoff, A. Meary & A. Szöke

  6. AP-HP, Hôpital H. Mondor - A. Chenevier, Pôle de Psychiatrie, Créteil, 94000, France

    F. Schurhoff, A. Meary & A. Szöke

  7. AP-HP, Hôpital H. Mondor - A. Chenevier, Centre de Référence Maladie de Huntington, Créteil, 94000, France

    A. C. Bachoud-Lévi & P. Maison

  8. IMRB - Inserm U955, Equipe 1, Neuropsychologie Interventionnelle, Faculté de Médecine de Créteil, 8 rue du général Sarrail, 94011, Créteil, France

    P. Maison

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  1. G. Désaméricq
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  2. F. Schurhoff
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Corresponding author

Correspondence to P. Maison.

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Contributions of authors statement

Drs Désaméricq and Maison designed the study and independently inspected all reports. Dr Désaméricq undertook the statistical analysis, and wrote the first draft of the manuscript. Drs Schürhoff and Maison made substantial contributions to the analysis and interpretation of data. All authors contributed to and have approved the final manuscript.

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Désaméricq, G., Schurhoff, F., Meary, A. et al. Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol 70, 127–134 (2014). https://doi.org/10.1007/s00228-013-1600-y

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  • DOI: https://doi.org/10.1007/s00228-013-1600-y

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