Comparative Effectiveness of Antipsychotic Drugs for Rehospitalization in Schizophrenia—A Nationwide Study With 20-Year Follow-up

Abstract

Very little is known about the comparative long-term effectiveness of novel antipsychotics in relapse prevention, especially in first-episode schizophrenia. Nationwide data from Finnish health care registers were gathered prospectively for all persons with periods of inpatient care due to schizophrenia in Finland during 1972–2014. Altogether 62250 persons were included in the prevalent cohort, and 8719 in the incident (first-episode schizophrenia) cohort. The follow-up for antipsychotic use started at 1996 for the prevalent cohort, and at the first discharge from inpatient care for the incident cases. Within-individual Cox regression models for risk of psychiatric and all-cause hospitalization were constructed to compare risk during antipsychotic use and no use using individual as his/her own control to eliminate selection bias. With follow-up time up to 20 years (median = 14.1, interquartile range = 6.9–20.0), 59% of the prevalent cohort were readmitted to psychiatric inpatient care. Olanzapine long-acting injection (LAI; adjusted hazard ratio = 0.46, 95% confidence interval = 0.36–0.61), clozapine (0.51, 0.49–0.53), and paliperidone LAI (0.51, 0.40–0.66) were associated with the lowest risk of psychiatric rehospitalization in the prevalent cohort. Among first-episode patients, the lowest risks were observed for flupentixol LAI (0.24, 0.12–0.49), olanzapine LAI (0.26, 0.16–0.44), and perphenazine LAI (0.39, 0.31–0.50). Clozapine and LAIs were associated with the lowest risk of all-cause hospitalization in both cohorts. Clozapine and LAIs are the most effective treatments in preventing psychiatric and all-cause hospitalization among chronic and first-episode patients with schizophrenia.

Mortality in schizophrenia: 30‐year nationwide follow‐up study

“…Another difference between our study and previous studies from UK and Denmark is that clozapine use in Finland is substantially more common than anywhere else in the world, as reported in a comparison of 17 countries . We have previously found in Finnish settings that clozapine is the most effective oral antipsychotic for treating schizophrenia and this may explain the rather good survival of Finnish persons with schizophrenia.…”

Long‐acting antipsychotic medication as first‐line treatment of first‐episode psychosis with comorbid substance use disorder

“…Since EIS offer intensive outreach services, they often allow for treatment of relapses without hospitalization, which can explain the difference in relapse and rehospitalization rates. Finally, it is possible that the relapse and rehospitalization rates of our cohort are high because of the SUD comorbidity and their younger age compared to other studies (mean of 22.9 years old in our study; median age 36.2 for the incident cohort in Taipale et al, 2017; mean age of 44.9 for the prevalent cohort in Tiihonen et al, 2017), since both are risk factors for worse outcomes and SUD has been associated with higher relapse rates in FEP (Malla et al, 2008;Schoeler et al, 2017).…”

“…Long-acting injectable antipsychotics (LAI-AP) are effective in reducing relapses and hospitalizations compared to oral antipsychotics (OAP) in patients with psychotic illnesses (Alphs et al, 2015;Kishimoto, Nitta, Borenstein, Kane, & Correll, 2013;Leucht et al, 2011;Schreiner et al, 2015;Stip & Lachaine, 2018;Subotnik et al, 2015;Taipale, Mehtälä, Tanskanen, & Tiihonen, 2017;Tiihonen et al, 2006;Tiihonen et al, 2011;Tiihonen et al, 2017;Toll et al, 2015).…”

20‐year follow‐up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20)

“…The study population was identified based on the nationwide Hospital Discharge register, which is managed by the National Institute of Health and Welfare. The study cohort included all persons treated in inpatient hospital care due to schizophrenia in Finland during the period 1972‐2014. Schizophrenia was defined by discharge diagnosis (ICD‐10 codes F20 and F25; ICD‐9 and ICD‐8 codes 295*).…”

“…Antipsychotics are effective in preventing relapses in schizophrenia, according to both randomized controlled trials (RCTs) and observational studies representing real‐world patients with long follow‐up periods. However, antipsychotic use is associated with the risk of serious adverse events, such as tardive dyskinesia.…”