Published online Mar 19, 2022. doi: 10.5498/wjp.v12.i3.521
Peer-review started: September 22, 2021
First decision: November 8, 2021
Revised: December 14, 2021
Accepted: January 29, 2022
Article in press: January 29, 2022
Published online: March 19, 2022
It is important to compare the effectiveness of various antipsychotic agents in the treatment of schizophrenia. The Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) study directly compared three antipsychotics (amisulpride, aripiprazole and olanzapine) in patients with schizophrenia-spectrum disorders between October 20, 2011 and December 30, 2016. The inclusion and follow-up of the patients are now completed, and the main findings have been published. In this substudy, we examined response trajectories and possible predictors for belonging to the different response groups.
Schizophrenia is a serious illness with a heterogeneous course. Pharmacological treatment with antipsychotic drugs remains the cornerstone in the treatment of schizophrenia, yet it is not possible to predict its effect on individual patients. Finding predictors of medication response can enhance the quality of schizophrenia treatment and the development of more personalized medicine.
The main objective of this substudy was to define response trajectories after a one-year follow-up for patients randomized to the three studied antipsychotics. The secondary objective was to define predictors of belonging to the different response trajectories. After realizing these objectives, we could present some suggestions for better clinical practice. We could also suggest further research on switching antipsychotics and on factors that predicted nonresponse, such as unemployment, depression, and negative psychotic symptoms.
Our study was a cohort study with data from a clinical trial of three antipsychotics in a prospective, randomized, rater-blind design. We defined response trajectories by fitting a latent class mixed model with Positive and Negative Syndrome Scale (PANSS) total as a dependent variable, time as an independent fixed variable, and subject as a random intercept to our data. We used the Bayesian information criterion and entropy to select the best model, and the model with three latent classes and with time represented as visit number best fit the data. Response trajectories provide a better picture of the course of symptoms over time and are a relatively novel way of examining response in schizophrenia.
The finding that 87% of the participants had a good or strong response to antipsychotic treatment adds to the research evidence about the general effectiveness of antipsychotic drugs. The response after the first six weeks of treatment seems to indicate further response to antipsychotics. The results indicate the need for further research on switching antipsychotics in incomplete responders to avoid delays in treatment and to enhance the quality of treatment.
Antipsychotic treatment has a good effect in a vast majority of schizophrenia-spectrum patients enrolled in a randomized drug trial. Furthermore, the six-week response seemed to predict the effects through the one-year follow-up. This can indicate an antipsychotic switch in patients without a reduction in the PANSS total score of 30% from baseline to six weeks in treatment with nonclozapine antipsychotics. Another important conclusion is the favorable results for amisulpride in comparison to aripiprazole and olanzapine, which could encourage more frequent use of this drug in schizophrenia treatment.
Future research on schizophrenia treatment should be designed to develop more personalized medicine through the identification of response predictors.