Prospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Mar 19, 2022; 12(3): 521-532
Published online Mar 19, 2022. doi: 10.5498/wjp.v12.i3.521
Trajectories of response in schizophrenia-spectrum disorders: A one-year prospective cohort study of antipsychotic effectiveness
Petros Drosos, Erik Johnsen, Christoffer Andreas Bartz-Johannessen, Tor Ketil Larsen, Solveig Klæbo Reitan, Maria Rettenbacher, Rune Andreas Kroken
Petros Drosos, Tor Ketil Larsen, TIPS-Network for Clinical Research in Psychosis, Clinic For Adult Mental Health, Stavanger University Hospital, Stavanger 4011, Norway
Petros Drosos, Erik Johnsen, Christoffer Andreas Bartz-Johannessen, Rune Andreas Kroken, NORMENT, Division of Psychiatry, Haukeland University Hospital, Bergen 5036, Norway
Petros Drosos, Erik Johnsen, Tor Ketil Larsen, Rune Andreas Kroken, Department of Clinical Medicine, University of Bergen, Bergen 5007, Norway
Solveig Klæbo Reitan, Institute for Mental Health, St Olav's University Hospital, Trondheim 7030, Norway
Solveig Klæbo Reitan, Department of Mental Health, Norwegian University of Natural Science and Technology, Trondheim 7491, Norway
Maria Rettenbacher, Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck 6020, Austria
Author contributions: Johnsen E and Kroken RA designed the project; Bartz-Johannessen CA and Drosos P carried out the statistical analyses; Drosos P prepared the first draft; Johnsen E, Bartz-Johannessen CA, Larsen TK, Reitan SK and Rettenbacher M contributed to the manuscript; all authors have read and approved the final version of the manuscript.
Supported by Drosos P is a Research Fellow with a Grant From the Western Norway Regional Health Trust, No. 912140.
Institutional review board statement: The study was reviewed and approved by the Regional Committees for Medical and Health Research Ethics (REK), No. 2010/3387-6.
Clinical trial registration statement: This is a prospective cohort study using data from the randomized, controlled trial study, the Best Intro Study ( Identifier: NCT01446328).
Informed consent statement: All study participants, or their legal guardian, provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Petros Drosos, MD, Doctor, Research Fellow, TIPS-Network for Clinical Research in Psychosis, Clinic For Adult Mental Health, Stavanger University Hospital, Jan Johnsens Gate 12, Stavanger 4011, Norway.
Received: September 22, 2021
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
Research background

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.

Research motivation

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.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

Future research on schizophrenia treatment should be designed to develop more personalized medicine through the identification of response predictors.