Real world effectiveness of antipsychotic treatments in patients with schizophrenia

The comparative effectiveness of antipsychotic treatments for patients with schizophrenia has remained controversial despite extensive research. Until now, it has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapses. This is largely owing to the challange of including selected patient populations in randomised clinical trials (RTCs).

Because RCTs include only a fraction of the most adherent patients, they do not provide information on the real-world effectiveness of antipsychotic treatment.

Observational studies may overcome the above problem, however the main issue is often selection bias. Although major covariants such as age, sex, duration of illness, number of previous hospitalisations etc can be corrected for in statistical analysis, there are always residual confounding factors associated with the individual characteristics of each patient.

In a study by Tiihonen et al1, the authors sought to overcome this problem by using within-individual analysis, where each patient acts as their own control. For example, some individuals willing to use clozapine or long-acting injectable (LAI) antipsychotic medication may differ from other patients in the intrinsic severity of their illness or adherence with treatment. For these patients the potential bias is eliminated by comparing the risk during use of that specific medication with the risk during periods of non-treatment with that medication within the same individual.

To the authors knowledge, this is the first study to investigate the comparative effectiveness of antipsychotic treatments for patients with schizophrenia using within-individual Cox proportional hazard regression analysis.1


"This is the first real-world study of 29,823 patients with schizophrenia comparing the efficacy of antipsychotic treatment using within-individual Cox proportional hazard regression analysis"



The results showed that clozapine and LAIs are substantially more effective than other antipsychotics in reducing the risk of rehospitalisation or any treatment failure.1 More specifically, the risk of rehospitalisation was 22% lower during treatment with LAIs compared with corresponding oral formulations in the total cohort, and 32% lower in the incident cohort of newly diagnosed patients.1 These findings are in line with previous research by Alphs et al2, which indicates that the use of LAIs demonstrates the greatest benefit during the earliest  hase of the illness.

This study represents the first direct comparison of LAIs vs oral formulation of the same second-generation antipsychotic for patients with their first episode of schizophrenia. The authors found that LAIs were associated with 85% lower risk of relapse compared to the oral formulation of the same compound, suggesting that newly diagnosed patients gain the greatest benefit from treatment with long-acting injectable antipsychotic medication.



Real-world evidence study with 29,823 patients compared the effectiveness of antipsychotic treatment


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  1. Tiihonen J, Mittendorfer-Rutz E, Maila Majak et al. Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia. JAMA Psychiatry 2017 Jul 1;74(7):686-693
  2. Alphs L, Nasrallah HA, Bossie CA et al. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy. Int Clin Psychopharmacol. 2016 Jul;31(4):202-9