Treatments for Schizophrenia in Adults: A Systematic Review [Internet]

Rockville (MD): Agency for Healthcare Research and Quality (US); 2017 Oct. Report No.: 17(18)-EHC031-EF.


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 1 SR of 138 trials (N=47,189) and 24 trials (N=6,672) for SGAs versus SGAs, 1 SR of 111 trials (N=118,503) and 5 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 treatment, 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.

Publication types

  • Review

Grants and funding

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, Contract No. 290-2015-00009-I. Prepared by: Pacific Northwest Evidence-based Practice Center, Portland, OR