TY - JOUR
T1 - A New Intervention for Implementation of Pharmacogenetics in Psychiatry
T2 - A Description of the PSY-PGx Clinical Study
AU - Pelgrim, Teuntje A D
AU - Philipsen, Alexandra
AU - Young, Allan H
AU - Juruena, Mario
AU - Jimenez, Ester
AU - Vieta, Eduard
AU - Jukić, Marin
AU - Van der Eycken, Erik
AU - Heilbronner, Urs
AU - Moldovan, Ramona
AU - Kas, Martien J H
AU - Jagesar, Raj R
AU - Nöthen, Markus M
AU - Hoffmann, Per
AU - Shomron, Noam
AU - Kilarski, Laura L
AU - van Amelsvoort, Thérèse
AU - Campforts, Bea
AU - The Psy-PGx Consortium, The IMAGEN
AU - van Westrhenen, Roos
N1 - Funding Information:
E.V. has received grants and served as a consultant, advisor, or C.M.E. speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. R.v.W. has received a grant and served as an advisor or speaker for Baxter, Psyfar, Benecke, Illumina, Lundbeck, and SCEM outside the submitted work. P.H. receives a salary from Life & Brain, serves as a consultant from HMG System Engineering, and served as a speaker for Illumina and Beckman Coulter. Everything outside the submitted work. M.M.N. has received fees for membership in an advisory board from HMG Systems Engineering GmbH (Fürth, Germany), for membership in the Medical-Scientific Editorial Office of the Deutsches Ärzteblatt, for review activities from the European Research Council (ERC), and for serving as a consultant for EVERIS Belgique SPRL in a project of the European Commission (REFORM/SC2020/029). M.M.N. receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH. A.Y. independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Center in South London, Maudsley NHS Foundation Trust, and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The other authors have no conflicts of interest to declare related to the work above.
Funding Information:
The clinical study described in the study protocol is part of the PSY-PGx project ( www.PSY-PGx.org , accessed on 17 January 2024). This overarching project aims to combine the outcomes of the current work with existing pharmacogenetic biobank data to generate a medication prescription algorithm based on machine learning principles. A first medication algorithm will be based solely on existing biobank data of the UK Biobank [] and the seven Finnish Biobanks [], which will be further developed using the de-identified data from the current study. Moreover, the biobanks will be assessed to identify potential pharmacogenes and proxies for clinical outcomes. Besides pharmacogenetic factors, additional individual patient characteristics that mediate individual medication responses will be evaluated and included in the medication algorithm. Finally, the PSY-PGx consortium aims to set up a DNA biobank to allow for future pharmacogenetic research. The DNA biobank will be established in collaboration with Systasy Bioscience GmbH (Munich, Germany), which developed an extensive cellular biobank infrastructure comprising biological samples from patients with psychiatric disorders. An additional optional written consent is obtained from participants in order to use their data for these purposes. The PSY-PGx project is coordinated by chief principal investigator RvW at Parnassia Psychiatric Institute, comprises 16 global partners, and is funded by the European Union’s Horizon 2020 research and innovation program (grant agreement No 945151).
Publisher Copyright:
© 2024 by the authors.
PY - 2024/1/23
Y1 - 2024/1/23
N2 -
(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry.
(2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants
escitalopram and
sertraline or antipsychotics
risperidone and
aripiprazole according to the latest state-of-the-art international dosing recommendations for
CYP2C19 and
CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning.
(3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.
AB -
(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry.
(2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants
escitalopram and
sertraline or antipsychotics
risperidone and
aripiprazole according to the latest state-of-the-art international dosing recommendations for
CYP2C19 and
CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning.
(3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.
UR - http://www.scopus.com/inward/record.url?scp=85185965017&partnerID=8YFLogxK
U2 - 10.3390/ph17020151
DO - 10.3390/ph17020151
M3 - Article
C2 - 38399366
SN - 1424-8247
VL - 17
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 2
M1 - 151
ER -