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CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis

Wannasuphoprasit, Y; Andersen, SE; Arranz, MJ; Catalan, R; Jurgens, G; Kloosterboer, SM; Rasmussen, HB; ... Bramon, E; + view all (2022) CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis. Frontiers in Psychology , 12 , Article 768748. 10.3389/fpsyg.2021.768748. Green open access

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Abstract

Background: Antipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment. Methods: We conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups (poor, intermediate, normal/extensive, and ultra-rapid metabolizers, UMs). Results: Twelve studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers (PMs), 633 intermediate metabolizers (IMs), 1,272 normal metabolizers (NMs), and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were (i) PM versus NM; weight = –0.07 (95%CI: –0.49 to 0.35, p = 0.74), BMI = 0.40 (95%CI: –0.19 to 0.99, p = 0.19). (ii) IM versus NM; weight = 0.09 (95% CI: –0.04 to 0.22, p = 0.16) and BMI = 0.09 (95% CI: –0.24 to 0.41, p = 0.60). (iii) UM versus EM; weight = 0.01 (95% CI: –0.37 to 0.40, p = 0.94) and BMI = –0.08 (95%CI: –0.57 to 0.42, p = 0.77). Conclusion: Our systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health.

Type: Article
Title: CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fpsyg.2021.768748
Publisher version: http://dx.doi.org/10.3389/fpsyg.2021.768748
Language: English
Additional information: Copyright © 2022 Wannasuphoprasit, Andersen, Arranz, Catalan, Jurgens, Kloosterboer, Rasmussen, Bhat, Irizar, Koller, Polimanti, Wang, Zartaloudi, Austin-Zimmerman and Bramon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: CYP2D6, antipsychotic, antipsychotic-induced weight gain, mental health, personalized medicine, pharmacogenetic, weight gain
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10144610
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