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Accepted manuscript

Influence of CYP2D6 phenotype on adherence, adverse effects, and attitudes in aripiprazole and risperidone users

Published online by Cambridge University Press:  25 March 2025

Elina Hietala Open the ORCID record for Elina Hietala [Opens in a new window] ,
Anssi Solismaa ,
Markku Lähteenvuo ,
Ari V. Ahola-Olli ,
Katja Häkkinen ,
Kimmo Suokas ,
Erkki Isometsä ,
Jaana Suvisaari ,
Tuula Kieseppä  and
Minna Holm
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Elina Hietala*
Affiliation:
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Vanha Vaasa Hospital, Department of Forensic Psychiatry, Vaasa, Finland The Wellbeing Services County of Ostrobothnia, Department of Psychiatry, Seinäjoki, Finland
Anssi Solismaa
Affiliation:
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, Pirkanmaa Hospital District, Tampere, Finland
Markku Lähteenvuo
Affiliation:
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland
Ari V. Ahola-Olli
Affiliation:
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
Katja Häkkinen
Affiliation:
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland
Kimmo Suokas
Affiliation:
Faculty of Social Sciences, Tampere University, Tampere, Finland
Erkki Isometsä
Affiliation:
Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Jaana Suvisaari
Affiliation:
Mental Health Team, Finnish Institute for Health and Welfare, Helsinki, Finland
Tuula Kieseppä
Affiliation:
Hospital District of Helsinki and Uusimaa, Helsinki, Finland
Minna Holm
Affiliation:
Mental Health Team, Finnish Institute for Health and Welfare, Helsinki, Finland
Jari Tiihonen
Affiliation:
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden
Jouko Lönnqvist
Affiliation:
Finnish Institute for Health and Welfare (THL), Helsinki, Finland University of Helsinki, Helsinki, Finland
Jarmo Hietala
Affiliation:
University of Turku, Faculty of Medicine, Department of Clinical Medicine (Psychiatry), Turku, Finland Department of Psychiatry, Turku University Hospital, Turku, Finland
Asko Wegelius
Affiliation:
Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Kaisla Lahdensuo
Affiliation:
Mehiläinen, Helsinki, Finland
Willehard Haaki
Affiliation:
University of Turku, Faculty of Medicine, Department of Clinical Medicine (Psychiatry), Turku, Finland Department of Psychiatry, Turku University Hospital, Turku, Finland
Olli Kampman
Affiliation:
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, Pirkanmaa Hospital District, Tampere, Finland Department of Clinical Sciences, Psychiatry, Umeå University, Umeå SE-90187, Sweden University of Turku, Faculty of Medicine, Department of Clinical Medicine (Psychiatry), Turku, Finland The Wellbeing Services County of Ostrobothnia, Department of Psychiatry, Seinäjoki, Finland
SUPER-Finland study
Affiliation:
Broad Institute of MIT and Harvard, Cambridge, MA, USA Massachusetts General Hospital Massachusetts General Hospital, Boston, MA, USA Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland Department of psychiatry, Oulu University Hospital, Oulu, Finland Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland
*
Corresponding author: Elina Hietala, tel. +35850 474 2198, email: [email protected]
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Abstract

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Background:

Non-adherence and negative attitudes towards medication are major problems in treating psychotic disorders. Cytochrome P450 2D6 (CYP2D6) contributes to the metabolism of aripiprazole and risperidone. Variations in CYP2D6 activity may affect treatment response or adverse effects. The impact of these variations on adherence and medication attitudes is unclear.

Aims:

This study investigates the relationships between CYP2D6 phenotype, self-reported adherence, adverse effects, and attitudes among aripiprazole and risperidone users.

Methods:

This study analyzed data from the SUPER-Finland cohort of 10,474 adults with psychotic episodes, including 1,429 aripiprazole and 828 risperidone users. The Attitudes towards neuroleptic treatment (ANT) questionnaire assessed adherence and adverse effects in all patients, while medication-related attitudes were examined in a subgroup of 1,000 participants. Associations between CYP2D6 phenotypes and outcomes were analyzed using logistic regression and beta regression in aripiprazole and risperidone groups separately.

Results:

Among risperidone users, we observed no association between CYP2D6 phenotypes and adherence, adverse effects, or attitudes. Similarly, no link was found between adherence and CYP2D6 phenotypes among aripiprazole users. However, aripiprazole users with the ultrarapid CYP2D6 phenotype had more adverse effects (OR = 1.71, 95 % CI 1.03–2.90, p = 0.041). Among aripiprazole users, CYP2D6 ultrarapid phenotype was associated with less favorable attitudes towards antipsychotic treatment (β = -0.48, p = 0.023).

Conclusions:

We found preliminary evidence that the ultrarapid CYP2D6 phenotype is associated with increased adverse effects and negative attitudes towards antipsychotic medication among aripiprazole users. CYP2D6 phenotype did not influence adherence, adverse effects, or attitudes among risperidone users.

Keywords

Psychotic DisordersTreatment Adherence and ComplianceCytochrome P-450 CYP2D6PharmacogeneticsAntipsychotic Agents
Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 30
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology