Definitions and drivers of relapse in patients with schizophrenia: a systematic literature review

José M Olivares, Jan Sermon, Michiel Hemels, Andreas Schreiner, José M Olivares, Jan Sermon, Michiel Hemels, Andreas Schreiner

Abstract

Relapse in patients with schizophrenia has devastating repercussions, including worsening symptoms, impaired functioning, cognitive deterioration and reduced quality of life. This progressive decline exacerbates the burden of illness on patients and their families. Relapse prevention is identified as a key therapeutic aim; however, the absence of widely accepted relapse definition criteria considerably hampers achieving this goal. We conducted a literature review in order to investigate the reporting of relapses and the validity of hospitalization as a proxy for relapse in patients with schizophrenia. The primary aim was to assess the range and validity of methods used to define relapse in observational or naturalistic settings. The secondary aim was to capture information on factors that predicted or influenced the risk of relapse. A structured search of the PubMed database identified articles that discussed relapse, and hospitalization as a proxy of relapse, in patients with schizophrenia. National and international guidelines were also reviewed. Of the 150 publications and guidelines identified, 87 defined relapse and 62% of these discussed hospitalization. Where hospitalization was discussed, this was as a proxy for, or a component of, relapse in the majority of cases. However, hospitalization duration and type varied and were not always well defined. Scales were used to define relapse in 53 instances; 10 different scales were used and multiple scales often appeared within the same definition. There were 95 references to factors that may drive relapse, including non-adherence to antipsychotic medication (21/95), stress/depression (11/95) and substance abuse (9/95). Twenty-five publications discussed the potential of antipsychotic therapy to reduce relapse rates-continuous antipsychotic therapy was associated with reduced frequency and duration of hospitalization. Non-pharmacological interventions, such as psychoeducation and cognitive behavioural therapy, were also commonly reported as factors that may reduce relapse. In conclusion, this review identified numerous factors used to define relapse. Hospitalization was the factor most frequently used and represents a useful proxy for relapse when reporting in a naturalistic setting. Several factors were reported to increase the risk of relapse, and observation of these may aid the identification of at-risk patients.

Figures

Figure 1
Figure 1
Literature search process. The asterisk denotes that the final review process is described in detail in the main body of the text.
Figure 2
Figure 2
Reported components of the definition for relapse. Hospitalization [11,15-59]; Positive and Negative Syndrome Scale (PANSS) [7,15,17,18,60-72]; Clinical Global Impression (CGI) scale [17,18,26,30,52,57,60-62,65],[66,68,71,73,74]; exacerbation/re-emergence of symptoms [7,27,29,34,38,43,63,67],[75-81]; deliberate self-harm or violent behaviour, suicidal or homicidal ideation, arrest [18,23,27,43,49,50,57,65],[66,71,74,82-84]; Brief Psychiatric Rating Scale (BPRS) [28,43,71,76,84-91]; change of medication or patient management [18,27,38,41,56,66,75,92]; exacerbation/re-emergence of symptoms leading to hospitalization [20,66,92-96]; clinical assessment of patient notes [38,57,88]; International Classification of Diseases (ICD) criteria [70,89,97]; Global Assessment of Functioning (GAF) [64,72]; physician interview and/or assessment [86,98]; Present State Examination (PSE) [84]; Global Assessment Scale (GAS) [84]; Target Symptoms Ratings Scale (TSRS) [76]; Psychiatric Assessment Scale (PAS) [99]; scale for the assessment of positive symptoms [86]; social functioning [75]; Social and Occupational Functioning Assessment Scale (SOFAS) [60].
Figure 3
Figure 3
Potential drivers of relapse. Adherence problems [2,6,7,13,17,25,26,31],[34,45,47,53,57,76,85,100-105]; stress, depression, depressive symptoms, neurosis [2,6,7,12,55,59,70,97],[106-108]; substance abuse [2,6,7,21,31,57,59,83],[97]; lifestyle factors [7,12,21,38,79,109,110]; hospitalization or relapse history [21,31,38,40,57,59,97]; treatment-related issues [6,7,28,43,61,70,111]; treatment interruption or delay [2,6,12,75,85,112,113]; disease-related factors [57,70,83,85,97,114]; quetiapine, anticholinergics, mood stabilizers (MS), oral neuroleptics, anxiolytics or hypnotics [21,31,51,55]; male gender [30,37,83,115]; use of first-generation antipsychotics (FGA) vs second-generation antipsychotics (SGA) [30,85,116]; outpatient vs inpatient [29,39]; poor patient insight [20,83]; younger age [57,83]; generic vs branded medication [117]; reduced compliance/family involvement in Information Technology Aided Relapse Prevention in Schizophrenia (ITAREPS) programme [53]; depot antipsychotics [76].
Figure 4
Figure 4
Factors that may reduce relapse rates. Individual citations of each factor: a single reference may include citations of more than one factor. The antipsychotic medication category does not include the other pharmacological therapy factors. Non-pharmacological therapies [4-6,11,14-16,27,32,41,42,64],[82,84,92,118-121]; antipsychotic medication [4,6,23,54,81,122-127]; risperidone/risperidone long-acting injectable (RLAI) specifically [22-24,35,65,74,128-131]; medication compliance [25,33,132,133]; Information Technology Aided Relapse Prevention in Schizophrenia (ITAREPS) [52]; good patient insight [134]; early detection [135]; greater frequency of electroconvulsive therapy (ECT) [90]; olanzapine specifically [21].

References

    1. Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day R, Bertelsen A. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychol Med Monogr Suppl. 1992;12:1–97.
    1. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: acute treatment of schizophrenia. World J Biol Psychiatry. 2005;12:132–191.
    1. Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;12:441–449.
    1. National Institute for Clinical Excellence. Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care (Update). National Clinical Practice Guidelines Number 82. London: NICE; 2009. p. 210.
    1. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: long-term treatment of schizophrenia. World J Biol Psychiatry. 2006;12:5–40.
    1. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;12(Suppl 2):1–56.
    1. Taylor M, Chaudhry I, Cross M, McDonald E, Miller P, Pilowsky L, Strickland P. Towards consensus in the long-term management of relapse prevention in schizophrenia. Hum Psychopharmacol. 2005;12:175–181.
    1. Kane JM. Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry. 2007;12(Suppl 14):27–30.
    1. Kane JM. Treatment adherence and long-term outcomes. CNS Spectr. 2007;12:21–26.
    1. Awad AG, Voruganti LN. The burden of schizophrenia on caregivers: a review. Pharmacoeconomics. 2008;12:149–162.
    1. Malik N, Kingdon D, Pelton J, Mehta R, Turkington D. Effectiveness of brief cognitive-behavioral therapy for schizophrenia delivered by mental health nurses: relapse and recovery at 24 months. J Clin Psychiatry. 2009;12:201–207.
    1. Muller N. Mechanisms of relapse prevention in schizophrenia. Pharmacopsychiatry. 2004;12(Suppl 2):S141–S147.
    1. Samalin L, Blanc O, Llorca PM. Optimizing treatment of schizophrenia to minimize relapse. Expert Rev Neurother. 2010;12:147–150.
    1. Dixon LB, Perkins DO, Calmes C. Guideline Watch (September 2009): Practice Guideline for the Treatment of Patients with Schizophrenia. APA Practice Guidelines. Arlington: APA; 2009. pp. 1–10.
    1. Bechdolf A, Knost B, Kuntermann C, Schiller S, Klosterkotter J, Hambrecht M, Pukrop R. A randomized comparison of group cognitive-behavioural therapy and group psychoeducation in patients with schizophrenia. Acta Psychiatr Scand. 2004;12:21–28.
    1. Bechdolf A, Kohn D, Knost B, Pukrop R, Klosterkotter J. A randomized comparison of group cognitive-behavioural therapy and group psychoeducation in acute patients with schizophrenia: outcome at 24 months. Acta Psychiatr Scand. 2005;12:173–179.
    1. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med. 2002;12:16–22.
    1. Emsley R, Oosthuizen P, Koen L, Niehaus DJ, Medori R, Rabinowitz J. Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Clin Ther. 2008;12:2378–2386.
    1. Hong J, Windmeijer F, Novick D, Haro JM, Brown J. The cost of relapse in patients with schizophrenia in the European SOHO (Schizophrenia Outpatient Health Outcomes) study. Prog Neuropsychopharmacol Biol Psychiatry. 2009;12:835–841.
    1. Drake RJ, Dunn G, Tarrier N, Bentall RP, Haddock G, Lewis SW. Insight as a predictor of the outcome of first-episode nonaffective psychosis in a prospective cohort study in England. J Clin Psychiatry. 2007;12:81–86.
    1. Haro JM, Novick D, Suárez D, Alonso J, Lépine JP, Ratcliffe M. Remission and relapse in the outpatient care of schizophrenia: three-year results from the Schizophrenia Outpatient Health Outcomes study. J Clin Psychopharmacol. 2006;12:571–578.
    1. Taylor M, Currie A, Lloyd K, Price M, Peperell K. Impact of risperidone long acting injection on resource utilization in psychiatric secondary care. J Psychopharmacol. 2008;12:128–131.
    1. Olivares JM, Rodriguez-Morales A, Diels J, Povey M, Jacobs A, Zhao Z, Lam A, Vega JC, Cuellar JA, de Castro FJ, Quintero CM, Martíin JF, Domínguez P, Ojeda JL, Cortés SS, Cala FI, Marín CG, Castro LM, Duaso MA, Albarracín JR, Vergara GN, Benítez AF, Cleries FM, Pérez-Brian JM, Aragón AB, Navarro JC, Biedma JA, de Pedro RB, González JF, López ME. et al.Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR) Eur Psychiatry. 2009;12:287–296.
    1. Peuskens J, Olivares JM, Pecenak J, Tuma I, Bij de Weg H, Eriksson L, Resseler S, Akhras K, Jacobs A. Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schiophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin. 2010;12:501–509.
    1. Ward A, Ishak K, Proskorovsky I, Caro J. Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: a retrospective database study. Clin Ther. 2006;12:1912–1921.
    1. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004;12:886–891.
    1. Pharoah FM, Mari JJ, Streiner D. Family intervention for schizophrenia. Cochrane Database Syst Rev. 2000;12:CD000088.
    1. Gaertner I, Gaertner HJ, Vonthein R, Dietz K. Therapeutic drug monitoring of clozapine in relapse prevention: a five-year prospective study. J Clin Psychopharmacol. 2001;12:305–310.
    1. Hickling FW, McCallum M, Nooks L, Rodgers-Johnson P. Outcome of first contact schizophrenia in Jamaica. West Indian Med J. 2001;12:194–197.
    1. Rabinowitz J, Lichtenberg P, Kaplan Z, Mark M, Nahon D, Davidson M. Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics. Am J Psychiatry. 2001;12:266–269.
    1. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv. 2001;12:805–811.
    1. Dyck DG, Hendryx MS, Short RA, Voss WD, McFarlane WR. Service use among patients with schizophrenia in psychoeducational multiple-family group treatment. Psychiatr Serv. 2002;12:749–754.
    1. Hayhurst KP, Brown P, Lewis SW. The cost-effectiveness of clozapine: a controlled, population-based, mirror-image study. J Psychopharmacol. 2002;12:169–175.
    1. Novák-Grubic V, Tavcar R. Predictors of noncompliance in males with first-episode schizophrenia, schizophreniform and schizoaffective disorder. Eur Psychiatry. 2002;12:148–154.
    1. de Sena EP, Santos-Jesus R, Miranda-Scippa A, Quarantini Lde C, Oliveira IR. Relapse in patients with schizophrenia: a comparison between risperidone and haloperidol. Rev Bras Psiquiatr. 2003;12:220–223.
    1. Thompson EE, Neighbors HW, Munday C, Trierweiler S. Length of stay, referral to aftercare, and rehospitalization among psychiatric inpatients. Psychiatr Serv. 2003;12:1271–1276.
    1. Usall J, Ochoa S, Araya S, Marquez M. Gender differences and outcome in schizophrenia: a 2-year follow-up study in a large community sample. Eur Psychiatry. 2003;12:282–284.
    1. Almond S, Knapp M, Francois C, Toumi M, Brugha T. Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry. 2004;12:346–351.
    1. Whitehorn D, Richard JC, Kopala LC. Hospitalization in the first year of treatment for schizophrenia. Can J Psychiatry. 2004;12:635–638.
    1. Miettunen J, Lauronen E, Veijola J, Koponen H, Saarento O, Isohanni M. Patterns of psychiatric hospitalizations in schizophrenic psychoses within the Northern Finland 1966 birth cohort. Nord J Psychiatry. 2006;12:286–293.
    1. Muirhead D, Harvey C, Ingram G. Effectiveness of community treatment orders for treatment of schizophrenia with oral or depot antipsychotic medication: clinical outcomes. Aust N Z J Psychiatry. 2006;12:596–605.
    1. Turkington D, Kingdon D, Rathod S, Hammond K, Pelton J, Mehta R. Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia. Br J Psychiatry. 2006;12:36–40.
    1. Xiang YQ, Zhang ZJ, Weng YZ, Zhai YM, Li WB, Cai ZJ, Tan QR, Wang CY. Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia. Schizophr Res. 2006;12:201–210.
    1. Buckley LA, Pettit T, Adams CE. Supportive therapy for schizophrenia. Cochrane Database Syst Rev. 2007;12 CD004716.
    1. Sun SX, Liu GG, Christensen DB, Fu AZ. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;12:2305–2312.
    1. Valencia M, Rascon ML, Juarez F, Murow E. A psychosocial skills training approach in Mexican out-patients with schizophrenia. Psychol Med. 2007;12:1393–1402.
    1. DosReis S, Johnson E, Steinwachs D, Rohde C, Skinner EA, Fahey M, Lehman AF. Antipsychotic treatment patterns and hospitalizations among adults with schizophrenia. Schizophr Res. 2008;12:304–311.
    1. Janicak PG, Wu JH, Mao L. Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials. Curr Med Res Opin. 2008;12:1807–1815.
    1. Rouillon F, Chartier F, Gasquet I. Strategies of treatment with olanzapine in schizophrenic patients during stable phase: results of a pilot study. Eur Neuropsychopharmacol. 2008;12:646–652.
    1. Zhu B, Ascher-Svanum H, Faries DE, Peng X, Salkever D, Slade EP. Costs of treating patients with schizophrenia who have illness-related crisis events. BMC Psychiatry. 2008;12:72.
    1. Haro JM, Ciudad A, Alonso J, Bousoño M, Suárez D, Novick D, Gilaberte I. Remission and relapse in the outpatient treatment of patients with schizophrenia. Outcomes at 3 years. Actas Esp Psiquiatr. 2008;12:187–196.
    1. Spaniel F, Vohlídka P, Kozený J, Novák T, Hrdlicka J, Motlová L, Cermák J, Höschl C. The Information Technology Aided Relapse Prevention Programme in Schizophrenia: an extension of a mirror-design follow-up. Int J Clin Pract. 2008;12:1943–1946.
    1. Spaniel F, Vohlídka P, Hrdlicka J, Kozený J, Novák T, Motlová L, Cermák J, Bednarík J, Novák D, Höschl C. ITAREPS: information technology aided relapse prevention programme in schizophrenia. Schizophr Res. 2008;12:312–317.
    1. Kim JH, Kim D, Marder SR. Time to rehospitalization of clozapine versus risperidone in the naturalistic treatment of comorbid alcohol use disorder and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2008;12:984–988.
    1. Gasquet I, Chartier F, Tcherny-Lessenot S, Lépine JP. The European Schizophrenia Outpatient Health Outcomes Study: observational study over 36 months of the French cohort of schizophrenic outpatients treated with antipsychotics. Rev Epidemiol Sante Publique. 2009;12:25–32.
    1. Olivares JM, Peuskens J, Pecenak J, Resseler S, Jacobs A, Akhras KS. Clinical and resource-use outcomes of risperidone long-acting injection in recent and long-term diagnosed schizophrenia patients: results from a multinational electronic registry. Curr Med Res Opin. 2009;12:2197–2206.
    1. Ascher-Svanum H, Zhu B, Faries DE, Salkever D, Slade EP, Peng X, Conley RR. The cost of relapse and the predictors of relapse in the treatment of schizophrenia. BMC Psychiatry. 2010;12:2.
    1. Hawley C, Turner M, Latif MA, Curtis V, Saleem PT, Wilton K. Switching stable patients with schizophrenia from depot and oral antipsychotics to long-acting injectable risperidone: reasons for switching and safety. Hum Psychopharmacol. 2010;12:37–46.
    1. Crown WH, Neslusan C, Russo PA, Holzer S, Ozminkowski R, Croghan T. Hospitalization and total medical costs for privately insured persons with schizophrenia. Adm Policy Ment Health. 2001;12:335–351.
    1. Glick ID, Berg PH. Time to study discontinuation, relapse, and compliance with atypical or conventional antipsychotics in schizophrenia and related disorders. Int Clin Psychopharmacol. 2002;12:65–68.
    1. Lipkovich I, Deberdt W, Csernansky JG, Buckley P, Peuskens J, Kollack-Walker S, Zhang Y, Liu-Seifert H, Houston JP. Predictors of risk for relapse in patients with schizophrenia or schizoaffective disorder during olanzapine drug therapy. J Psychiatr Res. 2007;12:305–310.
    1. Chrzanowski WK, Marcus RN, Torbeyns A, Nyilas M, McQuade RD. Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Psychopharmacology (Berl) 2006;12:259–266.
    1. Simonsen E, Friis S, Haahr U, Johannessen JO, Larsen TK, Melle I, Opjordsmoen S, Rund BR, Vaglum P, McGlashan T. Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors. Acta Psychiatr Scand. 2007;12:54–61.
    1. Lee SH, Choi TK, Suh S, Kim YW, Kim B, Lee E, Yook KH. Effectiveness of a psychosocial intervention for relapse prevention in patients with schizophrenia receiving risperidone via long-acting injection. Psychiatry Res. 2010;12:195–199.
    1. Emsley R, Medori R, Koen L, Oosthuizen PP, Niehaus DJ, Rabinowitz J. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol. 2008;12:210–213.
    1. Simpson GM, Mahmoud RA, Lasser RA, Kujawa M, Bossie CA, Turkoz I, Rodriguez S, Gharabawi GM. A 1-year double-blind study of 2 doses of long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2006;12:1194–1203.
    1. Bayle FJ, Misdrahi D, Llorca PM, Lancon C, Olivier V, Quintin P, Azorin JM. Acute schizophrenia concept and definition: investigation of a French psychiatrist population. Encéphale. 2005;12:10–17.
    1. Gleeson JF, Rawlings D, Jackson HJ, McGorry PD. Early warning signs of relapse following a first episode of psychosis. Schizophr Res. 2005;12:107–111.
    1. Kho KH, Blansjaar BA, de Vries, Babuskova D, Zwinderman AH, Linszen DH. Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia—an open label study. Eur Arch Psychiatry Clin Neurosci. 2004;12:372–379.
    1. Chabungbam G, Avasthi A, Sharan P. Sociodemographic and clinical factors associated with relapse in schizophrenia. Psychiatry Clin Neurosci. 2007;12:587–593.
    1. Knapp M, Locklear J, Jarbrink K. Impact of psychotic relapse definitions in assessing drug efficacy and costs: comparison of quetiapine XR, olanzapine and paliperidone ER. Curr Med Res Opin. 2009;12:1593–1603.
    1. Kim B, Lee SH, Choi TK, Suh S, Kim YW, Lee E, Yook KH. Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting. Prog Neuropsychopharmacol Biol Psychiatry. 2008;12:1231–1235.
    1. Dossenbach M, Arango-Dávila C, Silva IH, Landa E, Aguilar J, Caro O, Leadbetter J, Assunção S. Response and relapse in patients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol: 12-month follow-up of the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. J Clin Psychiatry. 2005;12:1021–1030.
    1. Olivares JM, Rodriguez-Martinez A, Burón JA, Onso-Escolano D, Rodriguez-Morales A. Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia: a 12- and 24-month follow-up from the e-STAR database in Spain. Appl Health Econ Health Policy. 2008;12:41–53.
    1. de Haan L, Linszen DH, Lenior ME, de Win ED, Gorsira R. Duration of untreated psychosis and outcome of schizophrenia: delay in intensive psychosocial treatment versus delay in treatment with antipsychotic medication. Schizophr Bull. 2003;12:341–348.
    1. Morken G, Widen JH, Grawe RW. Non-adherence to antipsychotic medication, relapse and rehospitalisation in recent-onset schizophrenia. BMC Psychiatry. 2008;12:32.
    1. Burns T, Fiander M, Audini B. A delphi approach to characterising “relapse” as used in UK clinical practice. Int J Soc Psychiatry. 2000;12:220–230.
    1. Bai YM, Ting CT, Chen JY, Chang WH, Wu B, Hung CH, Kuo LW. Equivalent switching dose from oral risperidone to risperidone long-acting injection: a 48-week randomized, prospective, single-blind pharmacokinetic study. J Clin Psychiatry. 2007;12:1218–1225.
    1. Mottaghipour Y, Pourmand D, Maleki H, Davidian L. Expressed emotion and the course of schizophrenia in Iran. Soc Psychiatry Psychiatr Epidemiol. 2001;12:195–199.
    1. Bradley GM, Couchman GM, Perlesz A, Nguyen AT, Singh B, Riess C. Multiple-family group treatment for English- and Vietnamese-speaking families living with schizophrenia. Psychiatr Serv. 2006;12:521–530.
    1. Morabia A, Ten Have T, Huguelet P, Ferrero F. Assessing efficacy of chronic therapy when disease is characterized by frequent relapses: the example of schizophrenia. J Clin Epidemiol. 2002;12:350–357.
    1. Pharoah F, Mari J, Rathbone J, Wong W. Family intervention for schizophrenia. Cochrane Database Syst Rev. 2006;12 CD000088.
    1. Csernansky JG, Schuchart EK. Relapse and rehospitalisation rates in patients with schizophrenia: effects of second generation antipsychotics. CNS Drugs. 2002;12:473–484.
    1. Pharoah FM, Rathbone J, Mari JJ, Streiner D. Family intervention for schizophrenia. Cochrane Database Syst Rev. 2003;12 CD000088.
    1. Uçok A, Polat A, Cakir S, Genç A. One year outcome in first episode schizophrenia. Predictors of relapse. Eur Arch Psychiatry Clin Neurosci. 2006;12:37–43.
    1. Leucht S, Barnes TR, Kissling W, Engel RR, Correll C, Kane JM. Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials. Am J Psychiatry. 2003;12:1209–1222.
    1. Nuechterlein KH, Miklowitz DJ, Ventura J, Gitlin MJ, Stoddard M, Lukoff D. Classifying episodes in schizophrenia and bipolar disorder: criteria for relapse and remission applied to recent-onset samples. Psychiatry Res. 2006;12:153–166.
    1. Linszen D, Dingemans P, Lenior M. Early intervention and a five year follow up in young adults with a short duration of untreated psychosis: ethical implications. Schizophr Res. 2001;12:55–61.
    1. Suzuki K, Awata S, Matsuoka H. One-year outcome after response to ECT in middle-aged and elderly patients with intractable catatonic schizophrenia. J ECT. 2004;12:99–106.
    1. Suzuki K, Awata S, Takano T, Ebina Y, Shindo T, Harada N, Matsuoka H. Adjusting the frequency of continuation and maintenance electroconvulsive therapy to prevent relapse of catatonic schizophrenia in middle-aged and elderly patients who are relapse-prone. Psychiatry Clin Neurosci. 2006;12:486–492.
    1. Suzuki K, Awata S, Takano T, Ebina Y, Iwasaki H, Matsuoka H. Continuation electroconvulsive therapy for relapse prevention in middle-aged and elderly patients with intractable catatonic schizophrenia. Psychiatry Clin Neurosci. 2005;12:481–489.
    1. Tomaras V, Mavreas V, Economou M, Ioannovich E, Karydi V, Stefanis C. The effect of family intervention on chronic schizophrenics under individual psychosocial treatment: a 3-year study. Soc Psychiatry Psychiatr Epidemiol. 2000;12:487–493.
    1. Lançon C, Auquier P, Nayt G, Reine G. Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS) Schizophr Res. 2000;12:231–239.
    1. Wahlbeck K, Cheine M, Essali MA. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2000;12:CD000059.
    1. Berglund N, Vahlne JO, Edman A. Family intervention in schizophrenia—impact on family burden and attitude. Soc Psychiatry Psychiatr Epidemiol. 2003;12:116–121.
    1. Chabannes JP, Bazin N, Leguay D, Nuss P, Peretti CS, Tatu P, Hameg A, Garay RP, Ferreri M. Two-year study of relapse prevention by a new education program in schizophrenic patients treated with the same antipsychotic drug. Eur Psychiatry. 2008;12:8–13.
    1. Moeller KE, Shireman TI, Liskow BI. Relapse rates in patients with schizophrenia receiving aripiprazole in comparison with other atypical antipsychotics. J Clin Psychiatry. 2006;12:1942–1947.
    1. Seuchter SA, Eisenacher M, Riesbeck M, Gaebel W, Köpcke W. Methods for predictor analysis of repeated measurements: application to psychiatric data. Methods Inf Med. 2004;12:184–191.
    1. Montero I, Asencio A, Hernández I, Masanet MJ, Lacruz M, Bellver F, Iborra M, Ruiz I. Two strategies for family intervention in schizophrenia: a randomized trial in a Mediterranean environment. Schizophr Bull. 2001;12:661–670.
    1. Law MR, Soumerai SB, Ross-Degnan D, Adams AS. A longitudinal study of medication nonadherence and hospitalization risk in schizophrenia. J Clin Psychiatry. 2008;12:47–53.
    1. Misdrahi D, Llorca PM, Lancon C, Bayle FJ. Compliance in schizophrenia: predictive factors, therapeutical considerations and research implications. Encéphale. 2002;12:266–272.
    1. Masand PS, Narasimhan M. Improving adherence to antipsychotic pharmacotherapy. Curr Clin Pharmacol. 2006;12:47–56.
    1. Hamann J, Cohen R, Leucht S, Busch R, Kissling W. Shared decision making and long-term outcome in schizophrenia treatment. J Clin Psychiatry. 2007;12:992–997.
    1. Charpentier A, Goudemand M, Thomas P. Therapeutic alliance, a stake in schizophrenia. Encéphale. 2009;12:80–89.
    1. Passerieux C, Caroli F, Giraud-Baro E. Persons suffering from schizophrenia and relapses. Encéphale. 2009;12:586–594.
    1. Norman RM, Malla AK, McLean TS, McIntosh EM, Neufeld RW, Voruganti LP, Cortese L. An evaluation of a stress management program for individuals with schizophrenia. Schizophr Res. 2002;12:293–303.
    1. Conley RR. The burden of depressive symptoms in people with schizophrenia. Psychiatr Clin North Am. 2009;12:853–861.
    1. Bottai T, Cotton I, Drigeard A, Vaglio V. [Prodromes of schizophrenia recurrence. Encéphale. 2009;12(Suppl 1):S33–S40.
    1. Kopelowicz A, Lopez SR, Zarate R, O'Brien M, Gordon J, Chang C, Gonzalez-Smith V. Expressed emotion and family interactions in Mexican Americans with schizophrenia. J Nerv Ment Dis. 2006;12:330–334.
    1. Fortney JC, Xu S, Dong F. Community-level correlates of hospitalizations for persons with schizophrenia. Psychiatr Serv. 2009;12:772–778.
    1. Faries DE, Ascher-Svanum H, Nyhuis AW, Kinon BJ. Clinical and economic ramifications of switching antipsychotics in the treatment of schizophrenia. BMC Psychiatry. 2009;12:54.
    1. Harman JS, Manning WG, Lurie N, Christianson JB. Association between interruptions in Medicaid coverage and use of inpatient psychiatric services. Psychiatr Serv. 2003;12:999–1005.
    1. Malla AK, Norman RM, Manchanda R, McLean TS, Harricharan R, Cortese L, Townsend LA, Scholten DJ. Status of patients with first-episode psychosis after one year of phase-specific community-oriented treatment. Psychiatr Serv. 2002;12:458–463.
    1. Haro JM, Novick D, Suárez D, Ochoa S, Roca M. Predictors of the course of illness in outpatients with schizophrenia: a prospective three year study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;12:1287–1292.
    1. Grossman LS, Harrow M, Rosen C, Faull R. Sex differences in outcome and recovery for schizophrenia and other psychotic and nonpsychotic disorders. Psychiatr Serv. 2006;12:844–850.
    1. Essali A, Al-Haj HN, Li C, Rathbone J. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2009;12:CD000059.
    1. Kluznik JC, Walbek NH, Farnsworth MG, Melstrom K. Clinical effects of a randomized switch of patients from clozaril to generic clozapine. J Clin Psychiatry. 2001;12(Suppl 5):14–17.
    1. Jones C, Cormac I, Mota J, Campbell C. Cognitive behaviour therapy for schizophrenia. Cochrane Database Syst Rev. 2000;12:CD000524.
    1. Pitschel-Walz G, Leucht S, Bauml J, Kissling W, Engel RR. The effect of family interventions on relapse and rehospitalization in schizophrenia-a meta-analysis. Schizophr Bull. 2001;12:73–92.
    1. Pekkala E, Merinder L. Psychoeducation for schizophrenia. Cochrane Database Syst Rev. 2002;12:CD002831.
    1. Pfammatter M, Junghan UM, Brenner HD. Efficacy of psychological therapy in schizophrenia: conclusions from meta-analyses. Schizophr Bull. 2006;12(Suppl 1):S64–S80.
    1. Thornley B, Adams CE, Awad G. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2000;12:CD000284.
    1. Sultana A, McMonagle T. Pimozide for schizophrenia or related psychoses. Cochrane Database Syst Rev. 2000;12:CD001949.
    1. Thornley B, Rathbone J, Adams CE, Awad G. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2003;12:CD000284.
    1. El-Sayeh HG, Morganti C. Aripiprazole for schizophrenia. Cochrane Database Syst Rev. 2006;12:CD004578.
    1. Rathbone J, McMonagle T. Pimozide for schizophrenia or related psychoses. Cochrane Database Syst Rev. 2007;12:CD001949.
    1. Adams CE, Awad G, Rathbone J, Thornley B. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2007;12:CD000284.
    1. Leal A, Rosillon D, Mehnert A, Jarema M, Remington G. Healthcare resource utilization during 1-year treatment with long-acting, injectable risperidone. Pharmacoepidemiol Drug Saf. 2004;12:811–816.
    1. Hunter RH, Joy CB, Kennedy E, Gilbody SM, Song F. Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Database Syst Rev. 2003;12:CD000440.
    1. Reveley MA, Libretto SE. Treatment outcome in patients with chronic schizophrenia during long-term administration with risperidone. J Clin Psychopharmacol. 2004;12:260–267.
    1. Parellada E. Long-acting injectable risperidone in the treatment of schizophrenia in special patient populations. Psychopharmacol Bull. 2007;12:82–100.
    1. Gilmer TP, Dolder CR, Lacro JP, Folsom DP, Lindamer L, Garcia P, Jeste DV. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004;12:692–699.
    1. Almerie MQ, Alkhateeb H, Essali A, Matar HE, Rezk E. Cessation of medication for people with schizophrenia already stable on chlorpromazine. Cochrane Database Syst Rev. 2007;12:CD006329.
    1. Sutton DL. Relapse signatures and insight: implications for CPNs. J Psychiatr Ment Health Nurs. 2004;12:569–574.
    1. Larsen TK, Melle I, Friis S, Joa I, Johannessen JO, Opjordsmoen S, Simonsen E, Vaglum P, McGlashan TH. One-year effect of changing duration of untreated psychosis in a single catchment area. Br J Psychiatry Suppl. 2007;12:s128–s132.
    1. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;12:603–609.
    1. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;12:31–41.
    1. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophrenia—a critical systematic review and meta-analysis of randomised long-term trials. Schizophrenia Res. 2011;12:83–92.
    1. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;12:2063–2071.
    1. Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, Borenstein M, Kane JM, Correll CU. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophrenia Bull. 2013. doi:10.1093/schbul/sbs150.
    1. Kishimoto T, Masahiro N, Borenstein M. Poster Presented at ACNP: 2012 December 2–6. Florida, USA; poster number 175.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe