Treatments for Adults with Schizophrenia: A Systematic Review [Entered Retrospectively]

Project Summary Title and Description

Treatments for Adults with Schizophrenia: A Systematic Review [Entered Retrospectively]
Objectives. This systematic review (SR) provides evidence on pharmacological and psychosocial treatments for schizophrenia. Data sources. MEDLINE®, the Cochrane Library databases, PsycINFO® and included studies through February 2017. Study selection. We included studies comparing second generation antipsychotics (SGA) with each other or with a first generation antipsychotic (FGA) and studies comparing psychosocial interventions with usual care in adults with schizophrenia. Data extraction. We extracted study design, year, setting, country, sample size, eligibility criteria, population, clinical and intervention characteristics, results, and funding source. Results. We included one SR of 138 trials (N=47,189) and 24 trials (N=6,672) for SGAs versus SGAs, one SR of 111 trials (N=118,503) and five trials (N=1,055) for FGAs versus SGAs, and 13 SRs of 271 trials (N=25,050) and 27 trials (n=6,404) for psychosocial interventions. Trials were mostly fair quality and strength of evidence was low or moderate. For drug therapy, the majority of the head to head evidence was on older SGAs, with sparse data on SGAs approved in the last 10 years (asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole), and recent long-acting injection [LAI] formulations of aripiprazole and paliperidone. Older SGAs were similar in measures of function, quality of life, mortality, and overall adverse events, except that risperidone LAI had better social function than quetiapine. Core illness symptoms were improved more with olanzapine and risperidone than asenapine, quetiapine, and ziprasidone and more with paliperidone than lurasidone and iloperidone; all were superior to placebo. Risperidone LAI and olanzapine had less withdrawal due to adverse events. Compared with olanzapine and risperidone, haloperidol, the most studied FGA, had similar improvement in core illness symptoms, negative symptoms, symptom response, and remission but greater incidence of adverse event outcomes. In comparison with usual care, most psychosocial interventions reviewed were more effective in improving intervention-targeted outcomes, including core illness symptoms. Various functional outcomes were improved more with assertive community care, cognitive behavioral therapy, family interventions, psychoeducation, social skills training, supported employment, and early interventions for first episode psychosis (FEP) than with usual care. Quality of life was improved more with cognitive behavioral therapy and early interventions for FEP than usual care. Relapse was reduced with family interventions, psychoeducation, illness self-management, family interventions, and early interventions for FEP. Conclusions. Most comparative evidence on pharmacotherapy relates to the older drugs, with clozapine, olanzapine, and risperidone superior on more outcomes than other SGAs. Older SGAs were similar to haloperidol on benefit outcomes but had fewer adverse event outcomes. Most psychosocial interventions improved functional outcomes, quality of life, and core illness symptoms, and several reduced relapse compared with usual care.
Authors of Report
Methodology description
Data sources. MEDLINE®, the Cochrane Library databases, PsycINFO® and included studies through February 2017. Study selection. We included studies comparing second generation antipsychotics (SGA) with each other or with a first generation antipsychotic (FGA) and studies comparing psychosocial interventions with usual care in adults with schizophrenia. Data extraction. We extracted study design, year, setting, country, sample size, eligibility criteria, population, clinical and intervention characteristics, results, and funding source.
This data for this project was entered retrospectively. Data Abstraction is available in the attached documents. The document named data abstraction includes abstraction of relevant data from each of the included studies for pharmacological and nonpharmacological interventions. The document named quality assessment includes an assessment of the quality of each of these included studies.
Funding Source
Agency for Healthcare Research and Quality. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. HHSA290201500009I.) AHRQ Publication No. XXX.

Key Questions

1. 1a. What are the comparative benefits and harms of pharmacological treatments for adults with schizophrenia?
2. 1b. How do the benefits and harms of pharmacological treatments for adults with schizophrenia vary by patient characteristics*? *Patient characteristics include age, sex, race, ethnicity, socioeconomic status, time since illness onset, prior treatment history, co-occurring psychiatric disorders, pregnancy, etc.
3. 2a. What are the benefits and harms of psychosocial and other nonpharmacological treatments for adults with schizophrenia?
4. 2b. How do the benefits and harms of nonpharmacological treatments for adults with schizophrenia vary by patient characteristics*? *Patient characteristics include age, sex, race, ethnicity, socioeconomic status, time since illness onset, prior treatment history, co-occurring psychiatric disorders, pregnancy, etc.

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.2005
Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.2011
Effectiveness of haloperidol, risperidone and olanzapine in the treatment of first-episode non-affective psychosis: results of a randomized, flexible-dose, open-label 1-year follow-up comparison.2011
Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis.2012
One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone and ziprasidone effectiveness in antipsychotic-naive patients with a first-episode psychosis.2012
Comparison of outcomes for African Americans, Hispanics, and Non-Hispanic Whites in the CATIE study.2013
Effects of ziprasidone and olanzapine on body composition and metabolic parameters: an open-label comparative pilot study.2013
Randomized trial of clozapine vs. risperidone in treatment-naïve first-episode schizophrenia: results after one year.2013
Subjective well-being in schizophrenia: a randomised controlled open-label 12-month non-inferiority study comparing quetiapine XR with risperidone (RECOVER).2013
Efficacy and tolerability of quetiapine versus haloperidol in first-episode schizophrenia: a randomized clinical trial.2013
Noninferiority of perphenazine vs. three second-generation antipsychotics in chronic schizophrenia.2014
An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial.2014
Open, randomized trial of the effects of aripiprazole versus risperidone on social cognition in schizophrenia.2014
Extended-release quetiapine fumarate (quetiapine XR) versus risperidone in the treatment of depressive symptoms in patients with schizoaffective disorder or schizophrenia: a randomized, open-label, parallel-group, flexible-dose study.2014
Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.2014
Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.2014
Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial.2014
Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study.2014
Pharmacogenetics of adverse events in schizophrenia treatment: comparison study of ziprasidone, olanzapine and perazine.2014
The influence of antipsychotic therapy on the cognitive functions of schizophrenic patients.-- Not Found --
Efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects: a randomized, double-blind, active parallel-controlled, multicenter clinical trial.2014
Randomized controlled trial comparing changes in serum prolactin and weight among female patients with first-episode schizophrenia over 12 months of treatment with risperidone or quetiapine.2014
Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole.
Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study.
Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.2015
Quetiapine versus aripiprazole in the management of schizophrenia.2015
Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia.2015
Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol.2016
Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: a randomized trial.2015
Association of a Schizophrenia Risk Variant at the DRD2 Locus With Antipsychotic Treatment Response in First-Episode Psychosis.
A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes.2015
The Comparative Effects of Risperidone Long-Acting Injection and Paliperidone Palmitate on Social Functioning in Schizophrenia: A 6-Month, Open-Label, Randomized Controlled Pilot Trial.2016
Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study.2016
The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study.2016
Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial.2016
Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial.2017
First-generation versus second-generation antipsychotics in adults: comparative effectiveness. Comparative effectiveness review No. 63. (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-200-10021.) AHRQ Publication No. 12-EHC054-EF
Second Generation Antipsychotic Drugs. Final Update 4 Report prepared by the Pacific Northwest Evidence-based Practice Center for the Drug Effectiveness Review Project. Oregon Health & Science University, Portland, Oregon, November 2013
Randomised controlled effectiveness trial of a needs-based psychosocial intervention service for carers of people with schizophrenia.1999
Management of negative symptoms among patients with schizophrenia attending multiple-family groups.2000
Case management for people with severe mental disorders.
Assertive community treatment for people with severe mental disorders.2000
Needs-based cognitive-behavioural family intervention for carers of patients suffering from schizophrenia: 12-month follow-up.2001
Outcome of case management based on the strengths model compared to standard care. A randomised controlled trial.2002
Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia.2002
Psychoeducation for schizophrenia.2002
The Hartford study of supported employment for persons with severe mental illness.
The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis.2004
Specialised care for early psychosis: symptoms, social functioning and patient satisfaction: randomised controlled trial.
A psychosocial skills training approach in Mexican out-patients with schizophrenia.2007
Assertive community treatment in the Netherlands: a randomized controlled trial.2007
A twelve-week randomized controlled study of the cognitive-behavioral Integrated Psychological Therapy program: positive effect on the social functioning of schizophrenic patients.2007
The use of individually tailored environmental supports to improve medication adherence and outcomes in schizophrenia.2008
Needs-based cognitive-behavioural family intervention for patients suffering from schizophrenia: 5-year follow-up of a randomized controlled effectiveness trial.2007
A randomized controlled trial of the effectiveness of the illness management and recovery program.2007
Comparing the efficacy of interventions that use environmental supports to improve outcomes in patients with schizophrenia.2008
Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial.2008
Course of illness in a sample of 265 patients with first-episode psychosis--five-year follow-up of the Danish OPUS trial.
Effects of cognitive behavioral therapy on work outcomes in vocational rehabilitation for participants with schizophrenia spectrum disorders.2009
Effectiveness of brief cognitive-behavioral therapy for schizophrenia delivered by mental health nurses: relapse and recovery at 24 months.2009
The short-term impact of generic versus individualized environmental supports on functional outcomes and target behaviors in schizophrenia.2009
Randomized trial of social rehabilitation and integrated health care for older people with severe mental illness.
Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study.2010
Family intervention for schizophrenia.2010
A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes.2011
Effectiveness of different modalities of cognitive remediation on symptomatological, neuropsychological, and functional outcome domains in schizophrenia: a prospective study in a real-world setting.2011
Does assertive community outreach improve social support? Results from the Lambeth Study of early-episode psychosis.2012
The ability of multifamily groups to improve treatment adherence in Mexican Americans with schizophrenia.2012
Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia.
Self-management education interventions for persons with schizophrenia: a meta-analysis.2013
Compensatory cognitive training for psychosis: effects in a randomized controlled trial.
REPYFLEC cognitive remediation group training in schizophrenia: Looking for an integrative approach.2012
Long-term outcomes of a randomized trial of integrated skills training and preventive healthcare for older adults with serious mental illness.
Psychosocial interventions for people with both severe mental illness and substance misuse.
The beneficial effects of combining pharmacological and psychosocial treatment on remission and functional outcome in outpatients with schizophrenia.2013
Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias.2014
Adapted cognitive-behavioural therapy required for targeting negative symptoms in schizophrenia: meta-analysis and meta-regression.2015
Efficacy of a family intervention program for prevention of hospitalization in patients with schizophrenia. A naturalistic multicenter controlled and randomized study in Spain.-- Not Found --
A randomized controlled trial comparing cognitive behavior therapy, cognitive adaptation training, their combination and treatment as usual in chronic schizophrenia.
Ten-year follow-up of the OPUS specialized early intervention trial for patients with a first episode of psychosis.
Persistence of effectiveness of cognitive remediation interventions in schizophrenia: a 1-year follow-up study.2015
One-year randomized controlled trial and follow-up of integrated neurocognitive therapy for schizophrenia outpatients.2015
The RAISE early treatment program for first-episode psychosis: background, rationale, and study design.
Supportive therapy for schizophrenia.
Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis.2015
Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program.2016
Cognitive remediation for negative symptoms of schizophrenia: A network meta-analysis.2017
Antipsychotic combination with psychosocial intervention on outcome of schizophrenia (acpios): rationale and design of the clinical trial2007
Results of a multisite randomized trial of supported employment interventions for individuals with severe mental illness.2005
Effectiveness of supported employment for individuals with schizophrenia: results of a multi-site, randomized trial2008
Supported employment for adults with severe mental illness.

Downloadable Data Content

  • XLSX Project Data