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Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up "Real World" Study in China.

ABSTRACT: Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083). Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.

SUBMITTER: Zhang L

PROVIDER: S-EPMC9234304 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe effectiveness of antipsychotic polypharmacy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical well-being.ObjectiveTo study the association of specific antipsychotic combinations with psychiatric rehospitalization.Design, setting, and participantsIn this nationwide cohort study, the risk of psychiatric rehospitalization was used as a marker for relapse among 62 250 patients with schizophrenia during the use of 29 different antipsychotic monotherapy and polypharmacy types between January 1, 1996, and December 31, 2015, in a comprehensive, nationwide cohort in Finland. We conducted analysis of the data from April 24 to June 15, 2018. Rehospitalization risks were investigated by using within-individual analyses to minimize selection bias.Main outcomes and measuresHazard ratio (HR) for psychiatric rehospitalization during use of polypharmacy vs during monotherapy within the same individual.ResultsIn the total cohort, including 62 250 patients, 31 257 individuals (50.2%) were men, and the median age was 45.6 (interquartile range, 34.6-57.9) years. The clozapine plus aripiprazole combination was associated with the lowest risk of psychiatric rehospitalization in the total cohort, being superior to clozapine, the monotherapy associated with the best outcomes, with a difference of 14% (HR, 0.86; 95% CI, 0.79-0.94) in the analysis including all polypharmacy periods, and 18% in the conservatively defined polypharmacy analysis excluding periods shorter than 90 days (HR, 0.82; 95% CI, 0.75-0.89; P < .001). Among patients with their first episode of schizophrenia, these differences between clozapine plus aripiprazole vs clozapine monotherapy were greater (difference, 22%; HR, 0.78; 95% CI, 0.63-0.96 in the analysis including all polypharmacy periods, and difference, 23%; HR, 0.77; 95% CI, 0.63-0.95 in the conservatively defined polypharmacy analysis). At the aggregate level, any antipsychotic polypharmacy was associated with a 7% to 13% lower risk of psychiatric rehospitalization compared with any monotherapy (ranging from HR, 0.87; 95% CI, 0.85-0.88, to HR, 0.93; 95% CI, 0.91-0.95; P < .001). Clozapine was the only monotherapy among the 10 best treatments. Results on all-cause and somatic hospitalization, mortality, and other sensitivity analyses were in line with the primary outcomes.Conclusions and relevanceCombining aripiprazole with clozapine was associated with the lowest risk of rehospitalization, indicating that certain types of polypharmacy may be feasible in the treatment of schizophrenia. Because add-on treatments are started when monotherapy is no longer sufficient to control for worsening of symptoms, it is likely that the effect sizes for polypharmacy are underestimates. Although the results do not indicate that all types of polypharmacy are beneficial, the current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia.

Project description:It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies.To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia.Prospectively gathered nationwide databases were linked to study the risk of rehospitalization and treatment failure from July 1, 2006, to December 31, 2013, among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29?823 patients in the total prevalent cohort; 4603 in the incident cohort of newly diagnosed patients). Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias. Traditional Cox proportional hazards multivariate regression was used for secondary analyses.Risk of rehospitalization and treatment failure (defined as psychiatric rehospitalization, suicide attempt, discontinuation or switch to other medication, or death).There were 29?823 patients (12?822 women and 17?001 men; mean [SD] age, 44.9 [12.0] years). During follow-up, 13?042 of 29?823 patients (43.7%) were rehospitalized, and 20?225 of 28?189 patients (71.7%) experienced treatment failure. The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR, 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR, 0.58; 95% CI, 0.44-0.77) compared with no use of antipsychotic medication. Oral flupentixol (HR, 0.92; 95% CI, 0.74-1.14), quetiapine (HR, 0.91; 95% CI, 0.83-1.00), and oral perphenazine (HR, 0.86; 95% CI, 0.77-0.97) were associated with the highest risk of rehospitalization. Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78; 95% CI, 0.72-0.84 in the total cohort; HR, 0.68; 95% CI, 0.53-0.86 in the incident cohort). Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine. The results of several sensitivity analyses were consistent with those of the primary analyses.Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations.

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Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up "Real World" Study in China.

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