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A randomized controlled trial of cognitive remediation and long-acting injectable risperidone after a first episode of schizophrenia: improving cognition and work/school functioning

Published online by Cambridge University Press:  28 September 2020

Keith H. Nuechterlein Open the ORCID record for Keith H. Nuechterlein [Opens in a new window] ,
Joseph Ventura ,
Kenneth L. Subotnik ,
Denise Gretchen-Doorly ,
Luana R. Turner ,
Laurie R. Casaus ,
John Luo ,
Michael L. Boucher ,
Jacqueline N. Hayata  and
Morris D. Bell
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Keith H. Nuechterlein*
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA Department of Psychology, University of California, Los Angeles, USA
Joseph Ventura
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Kenneth L. Subotnik
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Denise Gretchen-Doorly
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Luana R. Turner
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Laurie R. Casaus
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
John Luo
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Michael L. Boucher
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Jacqueline N. Hayata
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
Morris D. Bell
Affiliation:
Department of Psychiatry, Yale University, New Haven, CT, USA
Alice Medalia
Affiliation:
Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA
*
Author for correspondence: Keith H. Nuechterlein, Ph.D., E-mail: keithn@ucla.edu
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Abstract

Background

Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.

Methods

We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.

Results

Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.

Conclusions

These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.

Keywords

Cognitive trainingfunctional outcomelong-acting injectable antipsychotic
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 8 , June 2022 , pp. 1517 - 1526
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Bartzokis, G., Lu, P. H., Raven, E. P., Amar, C. P., Detore, N. R., Couvrette, A. J., … Nuechterlein, K. H. (2012). Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia. Schizophrenia Research, 140(1–3), 122–128.CrossRefGoogle ScholarPubMed
Becker, D. R., Swanson, S., Bond, G. R., & Merrens, M. R. (2008). Evidence-based supported employment fidelity review manual. Lebanon, N.H.: Dartmouth Psychiatric Research Center.Google Scholar
Bell, M., Bryson, G., Greig, T., Corcoran, C., & Wexler, B. E. (2001). Neurocognitive enhancement therapy with work therapy: Effects on neuropsychological test performance. Archives of General Psychiatry, 58(8), 763–768.CrossRefGoogle ScholarPubMed
Bowie, C. R., Grossman, M., Gupta, M., Oyewumi, L. K., & Harvey, P. D. (2014). Cognitive remediation in schizophrenia: Efficacy and effectiveness in patients with early versus long-term course of illness. Early Intervention in Psychiatry, 8(1), 32–38.CrossRefGoogle ScholarPubMed
Brar, J. S., Ganguli, R., Pandina, G., Turkoz, I., Berry, S., & Mahmoud, R. (2005). Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder. Journal of Clinical Psychiatry, 66(2), 205–212.CrossRefGoogle ScholarPubMed
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Erlbaum: Hillsdale, NJ.Google Scholar
Cornblatt, B. A., Auther, A. M., Niendam, T., Smith, C. W., Zinberg, J., Bearden, C. E., & Cannon, T. D. (2007). Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia. Schizophrenia Bulletin, 33(3), 688–702.CrossRefGoogle ScholarPubMed
Davidson, M., Galderisi, S., Weiser, M., Werbeloff, N., Fleischhacker, W. W., Keefe, R. S., … Kahn, R. S. (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(6), 675–682.Google Scholar
Eack, S. M., Greenwald, D. P., Hogarty, S. S., Cooley, S. J., DiBarry, A. L., Montrose, D. M., & Keshavan, M. S. (2009). Cognitive enhancement therapy for early-course schizophrenia: Effects of a two-year randomized controlled trial. Psychiatric Services, 60(11), 1468–1476.CrossRefGoogle ScholarPubMed
Eack, S. M., Hogarty, G. E., Greenwald, D. P., Hogarty, S. S., & Keshavan, M. S. (2007). Cognitive enhancement therapy improves emotional intelligence in early course schizophrenia: Preliminary effects. Schizophrenia Research, 89(1–3), 308–311.CrossRefGoogle ScholarPubMed
Evans, S., Newton, R., & Higgins, S. (2005). Nutritional intervention to prevent weight gain in patients commenced on olanzapine: A randomized controlled trial. Australian and New Zealand Journal of Psychiatry, 39(6), 479–486.Google ScholarPubMed
Fisher, M., Loewy, R., Carter, C., Lee, A., Ragland, J. D., Niendam, T., … Vinogradov, S. (2015). Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia. Schizophrenia Bulletin, 41(1), 250–258.CrossRefGoogle ScholarPubMed
Green, M. F. (2016). Impact of cognitive and social cognitive impairment on functional outcomes in patients with schizophrenia. Journal of Clinical Psychiatry, 77(Suppl 2), 8–11.CrossRefGoogle ScholarPubMed
Green, M. F., & Nuechterlein, K. H. (1999). Should schizophrenia be treated as a neurocognitive disorder? Schizophrenia Bulletin, 25, 309–319.CrossRefGoogle ScholarPubMed
Gretchen-Doorly, D., Subotnik, K. L., Kite, R. E., Alarcon, E., & Nuechterlein, K. H. (2009). Development and evaluation of a health promotion group for individuals with severe psychiatric disabilities. Psychiatric Rehabilitation Journal, 33(1), 56–59.Google Scholar
Gretchen-Doorly, D., Subotnik, K. L., Ventura, J., & Nuechterlein, K. H. (2012). Comparing Healthy Lifestyle Training and Cognitive Remediation in First-Episode Schizophrenia Patients: Six-Month Health Attitude and Independent Living Skills Outcomes. Paper presented at the The Society for Research in Psychopathology, Ann Arbor, Michigan, USA.Google Scholar
Harvey, P. D., & Bellack, A. S. (2009). Toward a terminology for functional recovery in schizophrenia: Is functional remission a viable concept? Schizophrenia Bulletin, 35(2), 300–306.CrossRefGoogle Scholar
Harvey, P. D., 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(10), 1888–1895.CrossRefGoogle Scholar
Holzer, L., Urben, S., Passini, C. M., Jaugey, L., Herzog, M. H., Halfon, O., & Pihet, S. (2014). A randomized controlled trial of the effectiveness of computer-assisted cognitive remediation (CACR) in adolescents with psychosis or at high risk of psychosis. Behavioural and Cognitive Psychotherapy, 42(4), 421–434.CrossRefGoogle ScholarPubMed
Insel, T. R. (2016). RAISE-ing Our expectations for first-episode psychosis. American Journal of Psychiatry, 173(4), 311–312.CrossRefGoogle ScholarPubMed
Keefe, R. S., & Harvey, P. D. (2012). Cognitive impairment in schizophrenia. Handbook of Experimental Pharmacology, 213, 11–37.CrossRefGoogle Scholar
Keefe, R. S., Seidman, L. J., Christensen, B. K., Hamer, R. M., Sharma, T., Sitskoorn, M. M., … Lieberman, J. A. (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(6), 985–995.CrossRefGoogle ScholarPubMed
Killackey, E. J., Jackson, H. J., & McGorry, P. D. (2008). Vocational intervention in first-episode psychosis: Individual placement and support versus treatment as usual. British Journal of Psychiatry, 193, 114–120.CrossRefGoogle Scholar
Kishimoto, T., Robenzadeh, A., Leucht, C., Leucht, S., Watanabe, K., Mimura, M., … Correll, C. U. (2014). Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: A meta-analysis of randomized trials. Schizophrenia Bulletin, 40(1), 192–213.CrossRefGoogle ScholarPubMed
Lee, R. S., Redoblado-Hodge, M. A., Naismith, S. L., Hermens, D. F., Porter, M. A., & Hickie, I. B. (2013). Cognitive remediation improves memory and psychosocial functioning in first-episode psychiatric out-patients. Psychological Medicine, 43(6), 1161–1173.CrossRefGoogle ScholarPubMed
Littrell, K., Hilligoss, N., Kirshner, C., Petty, R., & Johnson, C. (2003). The effects of an educational intervention on antipsychotic-induced weight gain. Journal of Nursing Scholarship, 35(3), 237–241.CrossRefGoogle ScholarPubMed
Marder, S. R., & Fenton, W. (2004). Measurement and treatment research to improve cognition in schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophrenia Research, 72(1), 5–9.CrossRefGoogle ScholarPubMed
McGurk, S. R., Mueser, K. T., & Pascaris, A. (2005). Cognitive training and supported employment for persons with severe mental illness: One-year results from a randomized controlled trial. Schizophrenia Bulletin, 31(4), 898–909.CrossRefGoogle ScholarPubMed
McGurk, S. R., Twamley, E. W., Sitzer, D. I., McHugo, G. J., & Mueser, K. T. (2007). A meta-analysis of cognitive remediation in schizophrenia. American Journal of Psychiatry, 164(12), 1791–1802.CrossRefGoogle Scholar
Medalia, A., Revheim, N., & Herlands, T. (2009). Cognitive remediation for psychological disorders. New York: Oxford University Press.CrossRefGoogle Scholar
Niendam, T. A., Bearden, C. E., Johnson, J. K., & Cannon, T. D. (2006). Global Functioning Scale: Role (GFS: Role). Rating scale. University of California, Los Angeles, Los Angeles. CA.Google Scholar
Nuechterlein, K. H., & Green, M. F. (2016). MATRICS Consensus Cognitive Battery manual, third edition. Los Angeles, CA: MATRICS Assessment, Inc.Google Scholar
Nuechterlein, K. H., Green, M. F., Kern, R. S., Baade, L. E., Barch, D. M., Cohen, J. D., … Marder, S. R. (2008). The MATRICS Consensus Cognitive Battery, part 1: Test selection, reliability, and validity. American Journal of Psychiatry, 165(2), 203–213.CrossRefGoogle ScholarPubMed
Nuechterlein, K. H., Subotnik, K. L., Turner, L. R., Ventura, J., Becker, D. R., & Drake, R. E. (2008). Individual placement and support for individuals with recent-onset schizophrenia: Integrating supported education and supported employment. Psychiatric Rehabilitation Journal, 31(4), 340–349.CrossRefGoogle ScholarPubMed
Nuechterlein, K. H., Subotnik, K. L., Ventura, J., Turner, L. R., Gitlin, M. J., Gretchen-Doorly, D., … Liberman, R. P. (2020). Enhancing return to work or school after a first episode of schizophrenia: The UCLA RCT of individual placement and support and workplace fundamentals module training. Psychological Medicine, 50(1), 20–28.CrossRefGoogle ScholarPubMed
Nuechterlein, K. H., Ventura, J., Subotnik, K. L., Hayata, J. N., Medalia, A., & Bell, M. D. (2014). Developing a cognitive training strategy for first-episode schizophrenia: Integrating bottom-up and top-down approaches. American Journal of Psychiatric Rehabilitation, 17(3), 225–253.CrossRefGoogle ScholarPubMed
Overall, J. E., Hollister, L. E., & Pichot, P. (1967). Major psychiatric disorder: A four-dimensional model. Archives of General Psychiatry, 16, 146–151.CrossRefGoogle ScholarPubMed
Puig, O., Penades, R., Baeza, I., De la Serna, E., Sanchez-Gistau, V., Bernardo, M., & Castro-Fornieles, J. (2014). Cognitive remediation therapy in adolescents with early-onset schizophrenia: A randomized controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry, 53(8), 859–868.CrossRefGoogle ScholarPubMed
Revell, E. R., Neill, J. C., Harte, M., Khan, Z., & Drake, R. J. (2015). A systematic review and meta-analysis of cognitive remediation in early schizophrenia. Schizophrenia Research, 168(1–2), 213–222.CrossRefGoogle ScholarPubMed
SAMHSA (2006). National consenus statement on mental health recovery. Rockville, MD: Substance Abuse and Mental Health Services Administration. National Mental Health Information Center.Google Scholar
Subotnik, K. L., Casaus, L. R., Ventura, J., Luo, J. S., Hellemann, G. S., Gretchen-Doorly, D., … Nuechterlein, K. H. (2015). Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia: A randomized clinical trial. JAMA Psychiatry, 72(8), 822–829.CrossRefGoogle ScholarPubMed
Subotnik, K. L., Nuechterlein, K. H., Kelly, K. A., Kupic, A. L., Brosemer, M., & Turner, L. R. (2008). Modified Version of the Social Adjustment Scale -- Work Outcome (originally by M. Weissman & S. Bothwell, 1976). Unpublished manuscript. University of California, Los Angeles, Los Angeles, CA.Google Scholar
Subotnik, K. L., Nuechterlein, K. H., Ventura, J., Gitlin, M. J., Marder, S., Mintz, J., … Singh, I. R. (2011). Risperidone nonadherence and return of positive symptoms in the early course of schizophrenia. American Journal of Psychiatry, 168(3), 286–292.CrossRefGoogle ScholarPubMed
Ueland, T., & Rund, B. R. (2004). A controlled randomized treatment study: The effects of a cognitive remediation program on adolescents with early onset psychosis. Acta Psychiatrica Scandinavica, 109(1), 70–74.CrossRefGoogle ScholarPubMed
Ventura, J., Subotnik, K. L., Gretchen-Doorly, D., Casaus, L., Boucher, M., Medalia, A., … Nuechterlein, K. H. (2019). Cognitive remediation can improve negative symptoms and social functioning in first-episode schizophrenia: A randomized controlled trial. Schizophrenia Research, 203, 24–31.CrossRefGoogle ScholarPubMed
Vinogradov, S., & Schulz, S. C. (2016). Behavioral and emerging pharmacologic treatment options for cognitive impairment in schizophrenia. Journal of Clinical Psychiatry, 77(Suppl 2), 12–16.CrossRefGoogle Scholar
Weber, M., & Wyne, K. (2006). A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. Schizophrenia Research, 83(1), 95–101.Google ScholarPubMed
Weiden, P., Mott, T., & Curcio, N. (1995). Recognition and management of neuroleptic noncompliance. In Shriqui, C. L., & Nasrallah, H. A. (eds), Contemporary issues in the treatment of schizophrenia (Vol. xxvi). Washington, DC: American Psychiatric Press, Inc, pp. 411–434.Google Scholar
Weissman, M. M., & Bothwell, S. (1976). Assessment of social adjustment by patient self-report. Archives of General Psychiatry, 33, 1111–1115.CrossRefGoogle ScholarPubMed
Woodward, N. D., Purdon, S. E., Meltzer, H. Y., & Zald, D. H. (2005). A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. International Journal of Neuropsychopharmacology, 8(3), 457–472.CrossRefGoogle Scholar
Wykes, T., Huddy, V., Cellard, C., McGurk, S. R., & Czobor, P. (2011). A meta-analysis of cognitive remediation for schizophrenia: Methodology and effect sizes. American Journal of Psychiatry, 168(5), 472–485.CrossRefGoogle ScholarPubMed
Wykes, T., Newton, E., Landau, S., Rice, C., Thompson, N., & Frangou, S. (2007). Cognitive remediation therapy (CRT) for young early onset patients with schizophrenia: An exploratory randomized controlled trial. Schizophrenia Research, 94(1–3), 221–230.CrossRefGoogle Scholar
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