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Cognitive performance during the first year of treatment in first-episode schizophrenia: a case–control study

  • M. R. Olivier (a1), S. Killian (a1), B. Chiliza (a1), L. Asmal (a1), R. Schoeman (a1), P. P. Oosthuizen (a1), M. Kidd (a2) and R. Emsley (a1)...

Abstract

Background

Several questions remain unanswered regarding the magnitude and time course of cognitive improvement in response to antipsychotic treatment. The purpose of this study was to assess changes in cognitive performance in antipsychotic-naive or minimally medicated patients with first-episode schizophrenia during the first 12 months of treatment, in a case–control design. Patients were treated with flupenthixol decanoate depot injection, according to a standard algorithm. The primary outcome measure was change in MATRICS Cognitive Consensus Battery (MCCB) composite score over 12 months.

Method

The sample comprised 92 patients and 100 healthy controls matched for age, sex, ethnicity and educational status. Cognitive function was assessed by means of the MCCB.

Results

A mixed-effects model identified a significant group × time effect (p ≤ 0.0001) for the MCCB composite score, with patients showing a greater degree of change than the controls. For the other MCCB domains there were significant group × time effects at adjusted significance level for attention and vigilance (p ≤ 0.0001), visual learning (p ≤ 0.0001), verbal learning (p = 0.005) and working memory (p ≤ 0.0001), but not for reasoning and problem solving (p = 0.04), speed of processing (p = 0.03) and social cognition (p = 0.06). There were moderate correlations between change in MCCB composite score and change in symptomatology as assessed by Positive and Negative Syndrome Scale factor analysis-derived domains.

Conclusions

Substantial improvements in cognitive function were observed over and above a practice effect, and were significantly correlated with improvements in psychopathology and functionality.

Copyright

Corresponding author

* Address for correspondence: R. Emsley, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg Campus, Cape Town 7505, South Africa. (Email: rae@sun.ac.za)

References

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Aas, M, Dazzan, P, Mondelli, V, Melle, I, Murray, RM, Pariante, CM (2014). A systematic review of cognitive function in first-episode psychosis, including a discussion on childhood trauma, stress, and inflammation. Frontiers in Psychiatry 4, 182.
Addington, D, Addington, J (1993). Assessing depression in schizophrenia: the Calgary Depression Scale. British Journal of Psychiatry 22 (Suppl.), 3944.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th edn. American Psychiatric Association: Washington, DC.
Barder, HE, Sundet, K, Rund, BR, Evensen, J, Haahr, U, Ten Velden, HW, Joa, I, Johannessen, JO, Langeveld, H, Larsen, TK, Melle, I, Opjordsmoen, S, Rossberg, JI, Simonsen, E, Vaglum, P, McGlashan, T, Friis, S (2013). Neurocognitive development in first episode psychosis 5 years follow-up: associations between illness severity and cognitive course. Schizophrenia Research 149, 6369.
Bilder, RM, Goldman, RS, Robinson, D, Reiter, G, Bell, L, Bates, JA, Pappadopulos, E, Willson, DF, Alvir, JM, Woerner, MG, Geisler, S, Kane, JM, Lieberman, JA (2000). Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. American Journal of Psychiatry 157, 549559.
Birchwood, M, Smith, J, Drury, V, Healy, J, Macmillan, F, Slade, M (1994). A self-report Insight Scale for psychosis: reliability, validity and sensitivity to change. Acta Psychiatrica Scandinavica 89, 6267.
Bowie, CR, Leung, WW, Reichenberg, A, McClure, MM, Patterson, TL, Heaton, RK, Harvey, PD (2008). Predicting schizophrenia patients’ real-world behavior with specific neuropsychological and functional capacity measures. Biological Psychiatry 63, 505511.
Bozikas, VP, Andreou, C (2011). Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature. Australian and New Zealand Journal of Psychiatry 45, 93108.
Buchanan, RW, Keefe, RS, Umbricht, D, Green, MF, Laughren, T, Marder, SR (2011). The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later? Schizophrenia Bulletin 37, 12091217.
Cannon-Spoor, HE, Potkin, SG, Wyatt, RJ (1982). Measurement of premorbid adjustment in chronic schizophrenia. Schizophrenia Bulletin 8, 470484.
Chen, EY, Hui, CL, Dunn, EL, Miao, MY, Yeung, WS, Wong, CK, Chan, WF, Tang, WN (2005). A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients. Schizophrenia Research 77, 99104.
Cohen, J (1988). Statistical Power Analysis for the Behavioural Sciences. Lawrence Erlbaum Associates: Hillsdale, NJ.
Davidson, M, Galderisi, S, Weiser, M, Werbeloff, N, Fleischhacker, WW, Keefe, RS, Boter, H, Keet, IP, Prelipceanu, D, Rybakowski, JK, Libiger, J, Hummer, M, Dollfus, S, Lopez-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens, J, Lindefors, N, Riecher-Rossler, A, Kahn, RS (2009). Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). American Journal of Psychiatry 166, 675682.
de Wit, H (2010). Flupenthixol. In Encyclopedia of Psychopharmacology: Springer Reference (ed. Stolerman, I. and Rice, L.), pp. 538539. Springer-Verlag: Berlin Heidelberg.
Desamericq, G, Schurhoff, F, Meary, A, Szoke, A, Macquin-Mavier, I, Bachoud-Levi, AC, Maison, P (2014). Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. European Journal of Clinical Pharmacology 70, 127134.
Dickinson, D, Ragland, JD, Gold, JM, Gur, RC (2008). General and specific cognitive deficits in schizophrenia: Goliath defeats David? Biological Psychiatry 64, 823827.
Ekerholm, M, Firus, WS, Fagerberg, T, Soderman, E, Terenius, L, Agartz, I, Jonsson, EG, Nyman, H (2012). Neurocognitive function in long-term treated schizophrenia: a five-year follow-up study. Psychiatry Research 200, 144152.
Emsley, R, Rabinowitz, J, Torreman, M (2003). The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophrenia Research 61, 4757.
First, MB, Spitzer, RLGM, Williams, LBW (1994). Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P). New York State Psychiatric Institute, Biometrics Research: New York.
Goldberg, TE, Goldman, RS, Burdick, KE, Malhotra, AK, Lencz, T, Patel, RC, Woerner, MG, Schooler, NR, Kane, JM, Robinson, DG (2007). Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Archive of General Psychiatry 64, 11151122.
Goldberg, TE, Keefe, RS, Goldman, RS, Robinson, DG, Harvey, PD (2010). Circumstances under which practice does not make perfect: a review of the practice effect literature in schizophrenia and its relevance to clinical treatment studies. Neuropsychopharmacology 35, 10531062.
Harvey, PD, Rabinowitz, J, Eerdekens, M, Davidson, M (2005). Treatment of cognitive impairment in early psychosis: a comparison of risperidone and haloperidol in a large long-term trial. American Journal of Psychiatry 162, 18881895.
International Conference on Harmonization (1996). ICH Harmonized Tripartite Guidelines for Good Clinical Practice. Brookwood Medical Publications Ltd: Richmond, Surrey.
Kahn, RS, Keefe, RS (2013). Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70, 11071112.
Kay, SR, Fizbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophrenia Bulletin 13, 261267.
Keefe, RS, Bilder, RM, Davis, SM, Harvey, PD, Palmer, BW, Gold, JM, Meltzer, HY, Green, MF, Capuano, G, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, Davis, CE, Hsiao, JK, Lieberman, JA (2007a). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Archives of General Psychiatry 64, 633647.
Keefe, RS, Buchanan, RW, Marder, SR, Schooler, NR, Dugar, A, Zivkov, M, Stewart, M (2013). Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? Schizophrenia Bulletin 39, 417435.
Keefe, RS, Seidman, LJ, Christensen, BK, Hamer, RM, Sharma, T, Sitskoorn, MM, Lewine, RR, Yurgelun-Todd, DA, Gur, RC, Tohen, M, Tollefson, GD, Sanger, TM, Lieberman, JA (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. American Journal of Psychiatry 161, 985995.
Keefe, RS, Seidman, LJ, Christensen, BK, Hamer, RM, Sharma, T, Sitskoorn, MM, Rock, SL, Woolson, S, Tohen, M, Tollefson, GD, Sanger, TM, Lieberman, JA (2006). Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biological Psychiatry 59, 97105.
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. Schizophrenia Bulletin 25, 201222.
Keefe, RS, Sweeney, JA, Gu, H, Hamer, RM, Perkins, DO, McEvoy, JP, Lieberman, JA (2007b). Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. American Journal of Psychiatry 164, 10611071.
Lieberman, JA, Perkins, DO, Jarskog, LF (2007). Neuroprotection: a therapeutic strategy to prevent deterioration associated with schizophrenia. CNS Spectrums 12, 113.
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. Biological Psychiatry 55, 10131022.
Nielsen, RE (2011). Cognition in schizophrenia – a systematic review. Drug Discovery Today: Therapeutic Strategies 8, 4348.
Nuechterlein, KH, Green, MF (2006). MATRICS Consensus Battery Manual. MATRICS Assessment Inc.: Los Angeles.
Nuechterlein, KH, Green, MF, Kern, RS, Baade, LE, Barch, DM, Cohen, JD, Essock, S, Fenton, WS, Frese III, FJ, Gold, JM, Goldberg, T, Heaton, RK, Keefe, RS, Kraemer, H, Mesholam-Gately, R, Seidman, LJ, Stover, E, Weinberger, DR, Young, AS, Zalcman, S, Marder, SR (2008). The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. American Journal of Psychiatry 165, 203213.
Nuechterlein, KH, Subotnik, KL, Green, MF, Ventura, J, Asarnow, RF, Gitlin, MJ, Yee, CM, Gretchen-Doorly, D, Mintz, J (2011). Neurocognitive predictors of work outcome in recent-onset schizophrenia. Schizophrenia Bulletin 37 (Suppl. 2), S33S40.
Porter, RJ, Bowie, CR, Jordan, J, Malhi, GS (2013). Cognitive remediation as a treatment for major depression: a rationale, review of evidence and recommendations for future research. Australian and New Zealand Journal of Psychiatry 47, 11651175.
Rajji, TK, Voineskos, AN, Butters, MA, Miranda, D, Arenovich, T, Menon, M, Ismail, Z, Kern, RS, Mulsant, BH (2013). Cognitive performance of individuals with schizophrenia across seven decades: a study using the MATRICS Consensus Cognitive Battery. American Journal of Geriatric Psychiatry 21, 108118.
Shen, X, Xia, J, Adams, CE (2012). Flupenthixol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD009777. DOI: 10.1002/14651858.CD009777.pub2.
Stern, R, White, T (2003). Neuropsychological Assessment Battery: Mazes. Psychological Assessment Resources, Incorporated: Lutz, FL.
Stip, E, Chouinard, S, Boulay, LJ (2005). On the trail of a cognitive enhancer for the treatment of schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 29, 219232.
Tandon, R, Nasrallah, HA, Keshavan, MS (2009). Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophrenia Research 110, 123.
Woodberry, KA, McFarlane, WR, Giuliano, AJ, Verdi, MB, Cook, WL, Faraone, SV, Seidman, LJ (2013). Change in neuropsychological functioning over one year in youth at clinical high risk for psychosis. Schizophrenia Research 146, 8794.
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. Schizophrenia Research 89, 211224.
World Health Organization (1998). Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychological Medicine 28, 551558.

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