Feasibility and Efficacy of a Psychological Therapy for Patients With a Schizophrenic Psychosis in an Inpatient Setting: Study Protocol of a Randomized Switch Controlled Trial

Mona Redlich Bossy, Daniel Mueller, Erich Seifritz, Stefan Vetter, Stephan T Egger, Mona Redlich Bossy, Daniel Mueller, Erich Seifritz, Stefan Vetter, Stephan T Egger

Abstract

Background: Schizophrenic psychoses are severe mental disorders. Despite advances in treatment, outcomes are still unsatisfactory. Pharmacological treatments are still limited, in particular regarding improvements in psychosocial functioning and neuro-cognitive impairment. In recent years new psychological therapies have been developed, demonstrating promising results. However, most of these interventions have been designed for and studied in outpatients; their efficacy and feasibility for patients requiring hospitalization is still unknown. Therefore, we have designed a clinical trial to compare a neuro-cognitive (Integrated Neuro-cognitive Treatment INT); a cognitive-behavioral (Integrated Psychological Therapy IPT); and a control (Cogpack CGP) intervention for patients with a schizophrenic psychosis hospitalized for treatment. Methods: In a three-parallel-arm, single-blind, randomized, controlled study, we compare INT, IPT, and CGP. Participants will take part in two weekly sessions of one intervention for at least 16 sessions. If due to randomization, participants are allocated to a treatment arm not suitable for them, they are allowed to switch intervention after four sessions. Based on a sample size calculation, recruitment will continue until 30 participants have completed the intervention for each treatment arm. Outcome Measurement: Primary outcomes are: change in symptom as measured by the Positive and Negative Syndrome Scale (PANSS), change in psychosocial functioning as assessed by the mini ICF-APP and neuro-cognitive performance, assessed by the Matrics Cognitive Consensus Battery (MCCB). Other outcomes of interest are the Brief Symptom Inventory (BSI) and the Health of the Nation Outcome Scales (HoNOS); together with prescribed medication, treatment retention and completion rates. Outcomes will be measured at baseline, 2 weeks into treatment (prior to a potential switch of intervention arm), post-treatment and at 6 and 12-month post-treatment follow-ups. Expected Outcomes: We expect an overall improvement; however, with differences in specific domains for each treatment arm, with those completing INT showing better outcomes than IPT and CGP, respectively. We anticipate that lower functioning participants will drift to CGP and higher functioning participants to INT. Conclusion: Due to the complexity of treatment for patients with a schizophrenic psychosis, we consider it crucial to compare different treatment options for those more severely affected, therefore, requiring inpatient treatment. Trial registration: www.clinicaltrials.gov (ID: NCT03316664; 17.10.2017).

Keywords: CBT for groups; INT; IPT; NCR; inpatient; randomized controlled trial; schizophrenic psychosis.

Copyright © 2020 Redlich Bossy, Mueller, Seifritz, Vetter and Egger.

Figures

Figure 1
Figure 1
Study flow chart.

References

    1. Van Os J, Kapur S. Schizophrenia. Lancet. (2009) 374:635–45. 10.1016/S0140-6736(09)60995-8
    1. Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. Schizophrenia. Nat Rev Dis Primers. (2015) 1:15067 10.1038/nrdp.2015.67
    1. Tandon R, Gaebel W, Barch DM, Bustillo J, Gur RE, Heckers S, et al. . Definition and description of schizophrenia in the DSM-5. Schizophr Res. (2013) 150:3–10. 10.1016/j.schres.2013.05.028
    1. Hegarty JD, Baldessarini RJ, Tohen M, Waternaux C, Oepen G. One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. (1994) 151:1409–16. 10.1176/ajp.151.10.1409
    1. Leucht S, Leucht C, Huhn M, Chaimani A, Mavridis D, Helfer B, et al. . Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry. (2017) 174:927–42. 10.1176/appi.ajp.2017.16121358
    1. Torniainen M, Mittendorfer-Rutz E, Tanskanen A, Bjorkenstam C, Suvisaari J, Alexanderson K, et al. . Antipsychotic treatment and mortality in schizophrenia Schizophr Bull. (2014) 41:656–63. 10.1093/schbul/sbu164
    1. Vanasse A, Blais L, Courteau J, Cohen AA, Roberge P, Larouche A, et al. . Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study. Acta Psychiatr Scand. (2016) 134:374–84. 10.1111/acps.12621
    1. Goff DC, Falkai P, Fleischhacker WW, Girgis RR, Kahn RM, Uchida H, et al. . The long-term effects of antipsychotic medication on clinical course in schizophrenia. Am J Psychiatry. (2017) 174:840–9. 10.1176/appi.ajp.2017.16091016
    1. Taipale H, Mehtälä J, Tanskanen A, Tiihonen J. Comparative effectiveness of antipsychotic drugs for rehospitalization in schizophrenia—A Nationwide study with 20-year follow-up. SchizophrBull. (2017) 44:1381–7. 10.1093/schbul/sbx176
    1. Bighelli I, Huhn M, Schneider-Thoma J, Krause M, Reitmeir C, Wallis S, et al. . Response rates in patients with schizophrenia and positive symptoms receiving cognitive behavioural therapy: a systematic review and single-group meta-analysis. BMC Psychiatry. (2018) 18:380. 10.1186/s12888-018-1964-8
    1. Bighelli I, Salanti G, Huhn M, Schneider-Thoma J, Krause M, Reitmeir C, et al. . Psychological interventions to reduce positive symptoms in schizophrenia: systematic review and network meta-analysis. World Psychiatry. (2018) 17:316–29. 10.1002/wps.20577
    1. Mcgurk SR, Twamley EW, Sitzer DI, Mchugo GJ, Mueser KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry. (2007) 164:1791–802. 10.1176/appi.ajp.2007.07060906
    1. Wykes T, Huddy V, Cellard C, Mcgurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. (2011) 168:472–85. 10.1176/appi.ajp.2010.10060855
    1. Müller DR, Roder V. Vom kognitiven Training zur Kognitiven Remediationstherapie: Nutzen und Grenzen. Verhaltenstherapie. (2017) 27:170–9. 10.1159/000479853
    1. Prikken M, Konings MJ, Lei WU, Begemann MJH, Sommer IEC. The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis. Schizophr Res. (2019) 204:368–74. 10.1016/j.schres.2018.07.034
    1. Lehman AF, Lieberman JA, Dixon LB, Mcglashan TH, Miller AL, Perkins DO, et al. . Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. (2004) 161 (2 Suppl.):1–56.
    1. Nice Psychosis and Schizophrenia in Adults: Prevention and Management. National Clinical Practice Guidelines Number CG178 (2014).
    1. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. . Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. (2016) 50:410–72. 10.1177/0004867416641195
    1. Kaiser S, Berger G, Conus P, Kawohl W, Müller TJ, Schimmelman BG, et al. SGPP Behandlungsempfehlungen Schizophrenie. Bern: SGPP; (2016).
    1. Grant PM, Huh GA, Perivoliotis D, Stolar NM, Beck AT. Randomized trial to evaluate the efficacy of cognitive therapy for low-functioning patients with schizophrenia. Arch Gen Psychiatry. (2012) 69:121–7. 10.1001/archgenpsychiatry.2011.129
    1. Grant PM, Bredemeier K, Beck AT. Six-month follow-up of recovery-oriented cognitive therapy for low-functioning individuals with schizophrenia. Psychiatr Serv. (2017) 68:997–1002. 10.1176/appi.ps.201600413
    1. Boden MT, Gaudiano BA, Walser RD, Timko C, Faustman W, Yasmin S, et al. . Feasibility and challenges of inpatient psychotherapy for psychosis: lessons learned from a veterans health administration pilot randomized controlled trial. BMC Res Notes. (2016) 9:376. 10.1186/s13104-016-2179-z
    1. Roder V, Brenner HD, Kienz N. Integriertes Psychologisches Therapieprogramm fur Schizophrene Patienten (IPT). Munich: Psychologie-Verl.; Union Munchen; (1988).
    1. Roder V, Mueller DR, Schmidt SJ. Effectiveness of integrated psychological therapy (IPT) for schizophrenia patients: a research update. Schizophr Bull. (2011) 37(Suppl. 2):S71–9. 10.1093/schbul/sbr072
    1. Roder V, Mueller DR, Mueser KT, Brenner HD. Integrated psychological therapy (IPT) for schizophrenia: is it effective? Schizophr Bull. (2006) 32(Suppl. 1):S81–93. 10.1093/schbul/sbl021
    1. Marker K. (2003). COGPACK Manual Version 5.9. Ladenburg: Marker Software.
    1. Roder V, Müller DS, Stefanie J, Lächler M. INT–Integrierte Neurokognitive Therapie bei Schizophren Erkrankten. Berlin; Heidelberg: Springer; (2013). 10.1007/978-3-642-21440-0
    1. Roder V, Müller DR, Schmidt SJ. Empirische Evidenz der INT. In: INT-Integrierte Neurokognitive Therapie bei Schizophren Erkrankten. Berlin; Heidelberg: Springer; (2013). p. 139–41. 10.1007/978-3-642-21440-0_5
    1. Mueller DR, Khalesi Z, Benzing V, Castiglione CI, Roder V. Does Integrated Neurocognitive Therapy (INT) reduce severe negative symptoms in schizophrenia outpatients? Schizophr Res. (2017) 188:92–7. 10.1016/j.schres.2017.01.037
    1. De Mare A, Cantarella M, Galeoto G. Effectiveness of integrated neurocognitive therapy on cognitive impairment and functional outcome for schizophrenia outpatients. Schizophr Res Treat. (2018) 2018:2360697. 10.1155/2018/2360697
    1. Roder VB, Hans D, Müller D. Integriertes Psychologisches Therapieprogramm bei Schizophren Erkrankten IPT. Weinheim: Julius Beltz; (2019).
    1. Green MF, Nuechterlein KH. The MATRICS initiative: developing a consensus cognitive battery for clinical trials. Schizophr Res. (2004) 72:1–3. 10.1016/j.schres.2004.09.006
    1. Rabinowitz J, Reichenberg A, Weiser M, Mark M, Kaplan Z, Davidson M. Cognitive and behavioural functioning in men with schizophrenia both before and shortly after first admission to hospital. Cross-sectional analysis. Br J Psychiatry. (2000) 177:26–32. 10.1192/bjp.177.1.26
    1. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). (2013). Washington, DC: American Psychiatric Association.
    1. Verhelst N, Van Avermaet P, Takala S, Figueras N, North B. Common European Framework of Reference for Languages: Learning, Teaching, Assessment. Cambridge: Cambridge University Press; (2009).
    1. Lindenmayer JP, Khan A, Mcgurk SR, Kulsa MKC, Ljuri I, Ozog V, et al. . Does social cognition training augment response to computer-assisted cognitive remediation for schizophrenia? Schizophr Res. (2018) 201:180–6. 10.1016/j.schres.2018.06.012
    1. Roder V, Brenner HD, Kienzle N. Integriertes psychologisches Therapieprogramm bei Schizophrenen Erkrankten IPT. Weinheim; Basel: Psychologie Verlagsunion; (2008).
    1. Mueller DR, Schmidt SJ, Roder V. One-year randomized controlled trial and follow-up of integrated neurocognitive therapy for schizophrenia outpatients. Schizophr Bull. (2015) 41:604–16. 10.1093/schbul/sbu223
    1. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. (1987) 13:261–76. 10.1093/schbul/13.2.261
    1. Linden M, Baron S. [The “Mini-ICF-Rating for Mental Disorders (Mini-ICF-P)”. A short instrument for the assessment of disabilities in mental disorders]. Rehabilitation. (2005) 44:144–51. 10.1055/s-2004-834786
    1. Derogatis L, Melisaratos N. The Brief Symptom Inventory: an introductory report. Psychol Med. (1983) 3:595–605. 10.1017/S0033291700048017
    1. Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; (1976).
    1. Jean Endicott P, Robert L, Spitzer M, Joseph L, Fleiss P, Jacob Cohen P. The global assessment scale. Arch Gen Psychiatry. (1976) 33:766–71. 10.1001/archpsyc.1976.01770060086012
    1. Wing J, Beevor A, Curtis R, Park S, Hadden S, Burns A. Health of the Nation Outcome Scales (HoNOS). Research and development. Br J Psychiatry. (1998) 172:11–8. 10.1192/bjp.172.1.11
    1. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res. (2005) 79:231–8. 10.1016/j.schres.2005.04.008
    1. Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, et al. . The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. (2008) 165:203–13. 10.1176/appi.ajp.2007.07010042
    1. Green MF, Nuechterlein KH, Kern RS, Baade LE, Fenton WS, Gold JM, et al. . Functional co-primary measures for clinical trials in schizophrenia: results from the MATRICS Psychometric and Standardization Study. Am J Psychiatry. (2008) 165:221–8. 10.1176/appi.ajp.2007.07010089
    1. Berk M, Ng F, Dodd S, Callaly T, Campbell S, Bernardo M, et al. The validity of the CGI severity and improvement scales as measures of clinical effectiveness suitable for routine clinical use. J Eval Clin Pract. (2008) 14:979–83. 10.1111/j.1365-2753.2007.00921.x
    1. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry. (2007) 4:28.
    1. Wing J, Curtis R, Beevor A. Health of the Nation Outcome Scales (HoNOS). Glossary for HoNOS score sheet. Br J Psychiatry. (1999) 174:432–4. 10.1192/bjp.174.5.432
    1. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. (2007) 39:175–91. 10.3758/BF03193146
    1. Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA. (2001) 285:1987–91. 10.1001/jama.285.15.1987
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. (2010) 340:c869. 10.1136/bmj.c869
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med. (2010) 8:18 10.1186/1741-7015-8-18
    1. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. . SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. (2013) 346:e7586. 10.1136/bmj.e7586
    1. Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. (2014) 348:g1687 10.1136/bmj.g1687
    1. Jääskeläinen E, Juola P, Hirvonen N, Mcgrath JJ, Saha S, Isohanni M, et al. . A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. (2012) 39:1296–306. 10.1093/schbul/sbs130
    1. Zimmerman M, Clark HL, Multach MD, Walsh E, Rosenstein LK, Gazarian D. Have treatment studies of depression become even less generalizable? A review of the inclusion and exclusion criteria used in placebo-controlled antidepressant efficacy trials published during the past 20 years. Mayo Clin Proc. (2015) 90:1180–6. 10.1016/j.mayocp.2015.06.016
    1. Zimmerman M, Holst CG, Clark HL, Multach M, Walsh E, Rosenstein LK, et al. The psychiatric inclusion and exclusion criteria in placebo-controlled monotherapy trials of bipolar depression: an analysis of studies of the past 20 years. CNS Drugs. (2016) 30:1209–18. 10.1007/s40263-016-0381-0
    1. Mitrushina M, Tomaszewski R. The effect of subjective perception of cognition on emotional functioning in adults with long-term neurological and neuropsychiatric disorders. Disabil Rehabil. (2019) 1–7. 10.1080/09638288.2019.1585490
    1. Borjesson S, Bostrom PK. “I want to know what it is used for”: Clients' perspectives on completing a routine outcome measure (ROM) while undergoing psychotherapy. Psychother Res. (2019) 30:337–47. 10.1080/10503307.2019.1630780
    1. Andreasen NC, Carpenter WTJr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. (2005) 162:441–9. 10.1176/appi.ajp.162.3.441
    1. Van Os J, Burns T, Cavallaro R, Leucht S, Peuskens J, Helldin L, et al. . Standardized remission criteria in schizophrenia. Acta Psychiatr Scand. (2006) 113:91–5. 10.1111/j.1600-0447.2005.00659.x
    1. Pinna F, Fiorillo A, Tusconi M, Guiso B, Carpiniello B. Assessment of functioning in patients with schizophrenia and schizoaffective disorder with the Mini-ICF-APP: a validation study in Italy. Int J Ment Health Syst. (2015) 9:37. 10.1186/s13033-015-0030-x
    1. Egger ST, Weniger G, Muller M, Bobes J, Seifritz E, Vetter S. Assessing the severity of functional impairment of psychiatric disorders: equipercentile linking the mini-ICF-APP and CGI. Health Qual Life Outcomes. (2019) 17:174. 10.1186/s12955-019-1235-5
    1. Patel MX, Arista IA, Taylor M, Barnes TR. How to compare doses of different antipsychotics: a systematic review of methods. Schizophr Res. (2013) 149:141–8. 10.1016/j.schres.2013.06.030
    1. Villeneuve K, Potvin S, Lesage A, Nicole L. Meta-analysis of rates of drop-out from psychosocial treatment among persons with schizophrenia spectrum disorder. Schizophr Res. (2010) 121:266–70. 10.1016/j.schres.2010.04.003
    1. Rakitzi S, Georgila P. The integrated psychological therapy and treatment-resistant schizophrenia: initial findings. Psychiatry. (2019) 1–14. 10.1080/00332747.2019.1616658
    1. Aloi M, De Filippis R, Grosso Lavalle F, Chiappetta E, Vigano C, Segura-Garcia C, et al. . Effectiveness of integrated psychological therapy on clinical, neuropsychological, emotional and functional outcome in schizophrenia: a RCT study. J Ment Health. (2018) 1–8. 10.1080/09638237.2018.1521948
    1. Bryce SD, Rossell SL, Lee SJ, Lawrence RJ, Tan EJ, Carruthers SP, et al. . Neurocognitive and Self-efficacy benefits of cognitive remediation in schizophrenia: a randomized controlled trial. J Int Neuropsychol Soc. (2018) 24:549–62. 10.1017/S1355617717001369
    1. Sartory G, Zorn C, Groetzinger G, Windgassen K. Computerized cognitive remediation improves verbal learning and processing speed in schizophrenia. Schizophr Res. (2005) 75:219–23. 10.1016/j.schres.2004.10.004
    1. Lindenmayer JP, Fregenti S, Kang G, Ozog V, Ljuri I, Khan A, et al. . The relationship of cognitive improvement after cognitive remediation with social functioning in patients with schizophrenia and severe cognitive deficits. Schizophr Res. (2017) 185:154–60. 10.1016/j.schres.2017.01.007
    1. Baldwin SA, Berkeljon A, Atkins DC, Olsen JA, Nielsen SL. Rates of change in naturalistic psychotherapy: contrasting dose-effect and good-enough level models of change. J Consult Clin Psychol. (2009) 77:203–11. 10.1037/a0015235
    1. Sharf J, Primavera LH, Diener MJ. Dropout and therapeutic alliance: a meta-analysis of adult individual psychotherapy. Psychotherapy. (2010) 47:637–45. 10.1037/a0021175
    1. Vancampfort D, Rosenbaum S, Schuch FB, Ward PB, Probst M, Stubbs B. Prevalence and predictors of treatment dropout from physical activity interventions in schizophrenia: a meta-analysis. Gen Hosp Psychiatry. (2016) 39:15–23. 10.1016/j.genhosppsych.2015.11.008

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