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

Antipsychotic drugs remain the mainstay of schizophrenia treatment; however, their effectiveness has been questioned, and it is not possible to predict the response to a specific antipsychotic drug in an individual patient. Thus, it is important to compare the effectiveness of the various antipsychotics and search for possible response predictors.


To investigate the effectiveness of antipsychotic drugs, we examined response trajectories and predictors for belonging to different trajectory groups.


The Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) trial compared the effectiveness of three atypical antipsychotics-amisulpride, aripiprazole, and olanzapine-in a prospective, semirandomized, rater-blind, head-to-head design. Adult participants with a schizophrenia spectrum disorder diagnosis, according to international classification of diseases, Tenth Revision (ICD-10) F20–29, were included. Participants were followed for a period of 12 mo, with assessments at baseline; after one, three and six weeks; and after three, six, nine and 12 mo. A latent class mixed model was fitted to our data. The three-trajectory model based on the Positive and Negative Syndrome Scale (PANSS) total score reduction was found to have adequate fit, and the study drugs, as well as various demographic and clinical parameters, were tested as predictors for belonging to the different trajectory groups.


Overall, 144 participants were included, and 41% completed the 12-mo study period. The largest trajectory group, consisting of 74% of participants, showed a PANSS total score reduction of 59% from baseline to 12 mo (Good response group). A trajectory group comprising 13% of participants had their PANSS total score reduced by 82.5% at 12 mo (Strong response group), while the last response trajectory group comprising 13% of the participants had a PANSS total score reduction of 13.6% (Slight response group). The largest part of the total reduction for the Good and Strong response groups occurred at six weeks of treatment, amounting to 45% and 48% reductions from baseline, respectively. The use of amisulpride predicted belonging to the Strong response group, while unemployment, depression, and negative psychotic symptoms at baseline increased the chance of belonging to the Slight response group, indicating a poor response to antipsychotic drug treatment.


Most of the participants (87%) had a good outcome after one year. Amisulpride users, more often than aripiprazole and olanzapine users, belonged to the response trajectory group with a strong response.

Keywords: Schizophrenia, Response, Trajectories, Treatment, Antipsychotic drugs

Core Tip: In this clinical trial of the three atypical antipsychotics amisulpride, aripiprazole, and olanzapine, we identified three trajectory groups of responses at the one-year follow-up. The majority of the study participants (87%) followed a trajectory of a good or strong response to antipsychotic drugs, while 13% showed a poor response. The use of amisulpride predicted belonging to the Strong response group. This antipsychotic should therefore be used more often in clinical practice. Unemployment, depression, and negative psychotic symptoms at baseline predicted nonresponse to antipsychotic drugs.