Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study

Abstract

Objective To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community. Design Prospective cohort study using national central registers. Setting Community care in Finland. Participants Nationwide cohort of 2230 consecutive adults hospitalised in Finland for the first time because of schizophrenia or schizoaffective disorder, January 1995 to December 2001. Main outcome measures Rates of discontinuation of drugs (all causes), rates of rehospitalisation, and mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs. Multivariate models and propensity score methods were used to adjust estimates of effectiveness. Results Initial use of clozapine (adjusted relative risk 0.17, 95% confidence interval 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol. During an average follow-up of 3.6 years, 4640 cases of rehospitalisation were recorded. Current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation. Use of haloperidol was associated with a poor outcome among women. Mortality was markedly raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276). Conclusions The effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation (for any reason) of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

“…Overall, our data regarding medication differences are similar to the Finnish data (Tiihonen et al, 2006(Tiihonen et al, , 2011, supporting the superior efficacy of a depot formulation and the efficacy rank order of oral olanzapine and risperidone. The significant differences in the time to discontinuation between the patients treated with oral SGAs or RLAI in this naturalistic study supports the conclusions of a metaanalysis that recent challenges of the benefits of depot formulations over oral formulations of antipsychotics may be related to the fact, that RCTs are less representative of real-world patients than naturalistic studies (Kishimoto et al, 2013).…”

“…The nationwide register-based study conducted in Finland by Tiihonen et al (2006) used an observational follow-up design and investigated discontinuation due to any cause as a principal measure of effectiveness. The Finnish study focused on the relative effectiveness of first and second generation antipsychotics in a nationwide patient cohort in community care after first hospitalization due to schizophrenia or schizoaffective disorder.…”

“…Our study is similar to Tiihonen et al (2006Tiihonen et al ( , 2011 study in that it used an observational follow-up design with all-cause treatment discontinuation as the principal effectiveness measure. However, unlike the Finnish study, our study included all patients with the diagnosis of schizophrenia and other psychotic disorders in Hungary who had been prescribed a new SGA during the inclusion period.…”

“…1 Istvan Bitter MD, PhD and Lajos Katona MS are co-first authors contributed equally to the article. 2 At the time of beginning of the study he worked as a psychiatry expert for NHIF.European Neuropsychopharmacology (2013Neuropsychopharmacology ( ) 23, 1383Neuropsychopharmacology ( -1390 with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al, 2006(Tiihonen et al, , 2011; namely the median times to all-cause medication discontinuation were o120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.…”

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration

“…If the Adjusted for sex, calendar year, age at onset of follow-up, number of previous relapses, duration of first hospitalisation, and length of follow-up (adjusted column) and additionally for a score of the propensity to start a treatment other than haloperidol (fully adjusted column). Table adapted from Tiihonen et al 156 2007 decision to include a variable in the model was based on the change in the estimate, it is important to report what change was considered sufficiently important to justify its inclusion. If a 'backward deletion' or 'forward inclusion' strategy was used to select confounders, explain that process and give the significance level for rejecting the null hypothesis of no confounding.…”