Comparison of Antipsychotic Drugs to Prevent Rehospitalization in Schizophrenia

Researchers aimed to clarify whether administration route influenced clinical outcomes, differentiating between oral and long-acting injection forms.

For people with both chronic and newly diagnosed schizophrenia, oral clozapine and several long-acting injection antipsychotic medications were superior to other medications in preventing hospitalization, whether for psychiatric or other reasons, according to findings published in Schizophrenia Bulletin.

Researchers in Finland examined a nationwide cohort to assess the long-term efficacy of antipsychotic medications at preventing relapse — particularly those prescribed after an initial schizophrenic episode. More specifically, the authors sought to clarify whether administration route influenced clinical outcomes, differentiating between oral and long-acting injection forms. The extended follow-up time (up to 20 years) was designed to improve on the findings of prior studies, which were based on shorter time periods.

Finnish health registers provided data on all inpatient hospitalizations related to schizophrenia that occurred from 1972 through 2014. During this period, 81,043 people were hospitalized for schizophrenia. Those with dementia (n=1166) were excluded from the study, along with those who either died during their initial hospitalization (n=2599) or before January 1, 1996 (n=15,028). The remaining individuals were divided into a prevalent cohort (n=62,250) consisting of those previously hospitalized and an incident cohort (n=8719) consisting of patients undergoing initial hospitalization for schizophrenia.

The primary outcome of the study was psychiatric hospitalization, and the secondary outcome was all-cause hospitalization. Cox regression models were plotted, with subjects serving as their own controls, measuring the risk for hospitalization in those receiving antipsychotic medications compared with hospitalization risk in those not receiving antipsychotic medications. Median follow-up time was 14.1 years (interquartile range 6.9-20.0), with 58.8% of the prevalent cohort being readmitted for inpatient psychiatric care during this period. The median follow-up time was 10.1 years (5.0-14.3) for the incident cohort, with 57.9% of this group readmitted for inpatient psychiatric care.

Within the prevalent cohort, patients at lowest risk for readmission to psychiatric inpatient care were those treated with olanzapine long-acting injection (adjusted hazard ratio=0.46; 95% CI=0.36-0.61), oral clozapine (0.51; 0.49-0.53), and paliperidone long-acting injection (0.51; 0.40-0.66). For the incident cohort, those at lowest risk were treated with flupentixol long-acting injection (0.24; 0.12-0.49), perphenazine long-acting injection (0.39; 0.31-0.50) and olanzapine long-acting injection (0.26; 0.16-0.44). In terms of all-cause hospitalization, the lowest risks were associated with oral clozapine and various long-acting injections, regardless of cohort.

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The investigators noted several strengths of their study, including within-individual analysis (acting as one’s own control), which removes potential selection bias and controls for disease duration, treatment order, and concomitant drug use; an unselected patient population, preventing follow-up loss; and representation of the actual outpatient schizophrenia population. Limitations of the study included the use of health registers, which do not offer extended clinical information such as quality of life measures, among others.

Although long-acting injections accounted for much of the risk reduction seen above, the researchers pointed out that this does not mean all long-acting injections are superior to all oral medications for preventing rehospitalization. However, the results do indicate that in the case of the Finnish population examined, long-acting injections and oral clozapine were more effective than other antipsychotic medications at preventing rehospitalization in patients with chronic and first-episode schizophrenia.


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 [published online December 20, 2017]. Schizophr Bull. doi:10.1093/schbul/sbx176