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      Guidelines for the Pharmacotherapy of Schizophrenia in Adults

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          Abstract

          <div class="section"> <a class="named-anchor" id="d14997002e190"> <!-- named anchor --> </a> <h5 class="section-title" id="d14997002e191">Objective:</h5> <p id="d14997002e193">The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains. </p> </div><div class="section"> <a class="named-anchor" id="d14997002e195"> <!-- named anchor --> </a> <h5 class="section-title" id="d14997002e196">Method:</h5> <p id="d14997002e198">Guidelines were developed using the ADAPTE process, which takes advantage of existing guidelines. Six guidelines were identified for adaptation, with recommendations extracted from each. For those specific to the pharmacotherapy of schizophrenia in adults, a working group selected between guidelines and recommendations to create an adapted guideline. </p> </div><div class="section"> <a class="named-anchor" id="d14997002e200"> <!-- named anchor --> </a> <h5 class="section-title" id="d14997002e201">Results:</h5> <p id="d14997002e203">Recommendations can be categorized into 6 areas that include 1) first-episode schizophrenia, 2) acute exacerbation, 3) relapse prevention and maintenance treatment, 4) treatment-resistant schizophrenia, 5) clozapine-resistant schizophrenia, and 6) specific symptom domains. For each category, recommendations are made based on the available evidence, which is discussed and linked to other established guidelines. </p> </div><div class="section"> <a class="named-anchor" id="d14997002e205"> <!-- named anchor --> </a> <h5 class="section-title" id="d14997002e206">Conclusions:</h5> <p id="d14997002e208">In most cases, evidence-based recommendations are made that can be used to guide current clinical treatment and decision making. Notably, however, there is a paucity of established evidence to guide treatment decision making in the case of clozapine-resistant schizophrenia, a subsample that represents a sizable proportion of those with schizophrenia. </p> </div>

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          Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review.

          Max Marshall, Shôn Lewis, Austin Lockwood … (2005)
          Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
          Article 0 comments Cited 309 times – based on 0 reviews     Review now
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            Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis.

            Stefan Leucht, Magdolna Tardy, Katja Komossa … (2012)
            Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues. We searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and ClinicalTrials.gov for those before June 8, 2011. We also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. Our primary outcome was relapse between 7 and 12 months. We also examined safety and various functional outcomes. We used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses. We identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27%vs placebo 64%; risk ratio [RR] 0·40, 95% CI 0·33-0·49; number needed to treat to benefit [NNTB] 3, 95% CI 2-3). Fewer patients given antipsychotic drugs than placebo were readmitted (10%vs 26%; RR 0·38, 95% CI 0·27-0·55; NNTB 5, 4-9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0·62, 95% CI -1·15 to -0·09) and fewer aggressive acts (2%vs 12%; RR 0·27, 95% CI 0·15-0·52; NNTB 11, 6-100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10%vs 6%; RR 2·07, 95% CI 2·31-3·25), had movement disorders (16%vs 9%; 1·55, 1·25-1·93), and experienced sedation (13%vs 9%; 1·50, 1·22-1·84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0·31, 95% CI 0·21-0·41) more than did oral drugs (0·46, 0·37-0·57; p=0·03); depot haloperidol (RR 0·14, 95% CI 0·04-0·55) and fluphenazine (0·23, 0·14-0·39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0·26, 0·17-0·39) than in most blinded studies (0·42, 0·35-0·51; p= 0·03). In a meta-regression, the difference between drug and placebo decreased with study length. Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side-effects. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality of these drugs. German Ministry of Education and Research. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia.

              Jari Tiihonen, Jari Haukka, Mark Z. Taylor … (2011)
              Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited. The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finland. The authors linked national databases of hospitalization, mortality, and antipsychotic prescriptions and computed hazard ratios, adjusting for the effects of sociodemographic and clinical variables, the temporal sequence of the antipsychotics used, and the choice of the initial antipsychotic for each patient. Of 2,588 patients, 1,507 (58.2%) collected a prescription for an antipsychotic during the first 30 days after hospital discharge, and 1,182 (45.7%, 95% confidence interval [CI]=43.7-47.6) continued their initial treatment for 30 days or longer. In a pairwise comparison between depot injections and their equivalent oral formulations, the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications (adjusted hazard ratio=0.36, 95% CI=0.17-0.75). Compared with oral risperidone, clozapine (adjusted hazard ratio=0.48, 95% CI=0.31-0.76) and olanzapine (adjusted hazard ratio=0.54, 95% CI=0.40-0.73) were each associated with a significantly lower rehospitalization risk. Use of any antipsychotic compared with no antipsychotic was associated with lower mortality (adjusted hazard ratio=0.45, 95% CI=0.31-0.67). In Finland, only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia. Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds. Among oral antipsychotics, clozapine and olanzapine were associated with more favorable outcomes. Use of any antipsychotic was associated with lower mortality.
              Article 0 comments Cited 187 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: The Canadian Journal of Psychiatry
                Abbreviated Title: Can J Psychiatry
                Publisher: SAGE Publications
                ISSN (Print): 0706-7437
                ISSN (Electronic): 1497-0015
                Publication date Created: July 13 2017
                Publication date Created: September 2017
                Publication date (Electronic): July 13 2017
                Publication date (Print): September 2017
                Volume: 62
                Issue: 9
                Pages: 604-616
                Affiliations
                [1 ]Departments of Psychiatry and Psychological Clinical Science, University of Toronto, Toronto, Canada
                [2 ]Schizophrenia Division, Continuing Care and Recovery Program, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
                [3 ]Department of Psychiatry, University of Calgary, Calgary, Canada
                [4 ]Hotchkiss Brain Institute and Matheson Centre for Mental Health Research and Education, Calgary, Canada
                [5 ]Department of Psychiatry, University of British Columbia, Vancouver, Canada
                [6 ]Psychopharmacology Research Unit, Department of Psychiatry, University of Calgary, Calgary, Canada
                [7 ]Department of Psychiatry, Dalhousie University, Halifax, Canada
                Article
                DOI: 10.1177/0706743717720448
                PMC ID: 5593252
                PubMed ID: 28703015
                SO-VID: 52b0ae4d-56b2-494b-a6f4-2392815e4786
                Copyright © © 2017
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