Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Apr 19, 2020; 10(4): 34-45
Published online Apr 19, 2020. doi: 10.5498/wjp.v10.i4.34
Moderators and mediators of antipsychotic response in delusional disorder: Further steps are needed
Alexandre González-Rodríguez, Armand Guàrdia, Diego José Palao, Javier Labad, Mary V Seeman
Alexandre González-Rodríguez, Armand Guàrdia, Diego José Palao, Javier Labad, Department of Mental Health, Parc Taulí University Hospital, Autonomous University of Barcelona, Sabadell 08280, Spain
Mary V Seeman, Department of Psychiatry, University of Toronto, Toronto, ON M5P 3L6, Canada
Author contributions: González-Rodríguez A and Guàrdia A conducted the original search and wrote the first draft of the paper; Palao DJ, Labad J and Seeman MV screened the selected articles and contributed to subsequent drafts of the manuscript.
Supported by Intensification of the Research Activity Grant from the Health Department of the Generalitat de Catalunya, No. SLT006/17/00012 to Labad J.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Mary V Seeman, DSc, FRCP (C), MD, Emeritus Professor, Department of Psychiatry, University of Toronto, 260 Heath Street West, Suite #605, Toronto, ON M5P 3L6, Canada.
Received: December 24, 2019
Peer-review started: December 27, 2019
First decision: February 20, 2020
Revised: March 4, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: April 19, 2020

Delusional disorder (DD) has been traditionally considered a relatively rare and treatment-resistant psychotic disorder. In the last decade, increasing attention has focused on therapeutic outcomes of individuals affected by this disorder. The aim of this paper is to provide a synthesis of the literature addressing two very important questions arising from DD research: (1) For which patients with DD do antipsychotic medications work best (the moderators of response); and (2) What variables best explain the relationship between such treatments and their effectiveness (the mediators of response). We searched PubMed and Google Scholar databases for English, German, French and Spanish language papers published since 2000. We also included a few classic earlier papers addressing this topic. Variables potentially moderating antipsychotic response in DD are gender, reproductive status, age, duration of illness, the presence of comorbidity (especially psychiatric comorbidity) and its treatment, brain structure, and genetics of neurochemical receptors and drug metabolizing enzymes. Antipsychotic and hormonal blood levels during treatment, as well as functional brain changes, are potential mediating variables. Some, but not all, patients with DD benefit from antipsychotic treatment. Understanding the circumstances under which treatment works best can serve to guide optimal management.

Keywords: Delusional disorder, Psychosis, Moderators, Mediators, Antipsychotic response

Core tip: Although patients with delusional disorder have traditionally been viewed as treatment-resistant, many do experience benefits from antipsychotic medications, but not all respond similarly. The identification of mediators and moderators of treatment response is clinically useful in that understanding under what circumstances treatment works best provides a reliable guide to effective management.