The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study

doi:10.3390/biomedicines12030494

. 2024 Feb 22;12(3):494.

doi: 10.3390/biomedicines12030494.

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study

Adriana Cojocaru^{1

2}, Adina Braha³, Roxana Jeleriu⁴, Nicoleta Ioana Andreescu⁴, Maria Puiu⁴, Luminita Ageu⁵, Roxana Folescu⁶, Carmen Lacramioara Zamfir⁷, Laura Alexandra Nussbaum¹

Affiliations

¹ Department of Neurosciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
² Doctoral School, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
³ Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
⁴ Department of Microscopic Morphology, Discipline of Genetics, Genomic Medicine Centre, "Victor Babeș" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
⁵ Mental Health Department for Children and Adolescents, "Louis Turcanu" Children's Emergency Hospital, 2 Doctor Iosif Nemoianu, 300011 Timisoara, Romania.
⁶ Department of Balneology, Medical Recovery and Rheumatology, Family Medicine Discipline, Center for Preventive Medicine, Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
⁷ Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.

PMID: 38540107
PMCID: PMC10968582
DOI: 10.3390/biomedicines12030494

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study

Adriana Cojocaru et al. Biomedicines. 2024.

. 2024 Feb 22;12(3):494.

doi: 10.3390/biomedicines12030494.

Authors

Adriana Cojocaru^{1

2}, Adina Braha³, Roxana Jeleriu⁴, Nicoleta Ioana Andreescu⁴, Maria Puiu⁴, Luminita Ageu⁵, Roxana Folescu⁶, Carmen Lacramioara Zamfir⁷, Laura Alexandra Nussbaum¹

Affiliations

¹ Department of Neurosciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
² Doctoral School, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
³ Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
⁴ Department of Microscopic Morphology, Discipline of Genetics, Genomic Medicine Centre, "Victor Babeș" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
⁵ Mental Health Department for Children and Adolescents, "Louis Turcanu" Children's Emergency Hospital, 2 Doctor Iosif Nemoianu, 300011 Timisoara, Romania.
⁶ Department of Balneology, Medical Recovery and Rheumatology, Family Medicine Discipline, Center for Preventive Medicine, Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
⁷ Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.

PMID: 38540107
PMCID: PMC10968582
DOI: 10.3390/biomedicines12030494

Abstract

Background: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme.

Methods: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan^® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment.

Results: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups.

Conclusions: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.

Keywords: PANSS score; adolescents; adverse reaction; atypical antipsychotics; cytochrome CYP2D6.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
Comparison of PANSS score dynamics according to antipsychotic therapy.

**Figure 2**
The dynamics of PANSS score during the 12-month follow-up according to genotype.

See this image and copyright information in PMC

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[1] Jody L., Brown D.A.B., Laurence M., Angela S. Psychosis in Children and Adolescents: Psych TLC Department of Psychiatry Division of Child & Adolescent Psychiatry University of Arkansas for Medical Sciences Psychiatric Research Institute. 2014. [(accessed on 6 August 2023)]. Available online: https://psychiatry.uams.edu/wp-content/uploads/2022/07/psychosis.pdf.

[2] Jody L., Brown D.A.B., Laurence M., Angela S. Psychosis in Children and Adolescents: Psych TLC Department of Psychiatry Division of Child & Adolescent Psychiatry University of Arkansas for Medical Sciences Psychiatric Research Institute. 2014. [(accessed on 6 August 2023)]. Available online: https://psychiatry.uams.edu/wp-content/uploads/2022/07/psychosis.pdf.

[3] McClellan J. Psychosis in Children and Adolescents. J. Am. Acad. Child Adolesc. Psychiatry. 2018;57:308–312. doi: 10.1016/j.jaac.2018.01.021. - DOI - PubMed

[4] McClellan J. Psychosis in Children and Adolescents. J. Am. Acad. Child Adolesc. Psychiatry. 2018;57:308–312. doi: 10.1016/j.jaac.2018.01.021. - DOI - PubMed

[5] Schulz S.C., Green M.F., Nelson K.J. Schizophrenia and Psychotic Spectrum Disorders. Volume XII. Oxford University Press; Oxford, NY, USA: 2016. 382p

[6] Schulz S.C., Green M.F., Nelson K.J. Schizophrenia and Psychotic Spectrum Disorders. Volume XII. Oxford University Press; Oxford, NY, USA: 2016. 382p

[7] Altamura C.A., Fagiolini A., Galderisi S., Rocca P., Rossi A. Schizophrenia today: Epidemiology, diagnosis, course and models of care. Off. J. Ital. Soc. Psychopathol. 2014;20:223–243.

[8] Altamura C.A., Fagiolini A., Galderisi S., Rocca P., Rossi A. Schizophrenia today: Epidemiology, diagnosis, course and models of care. Off. J. Ital. Soc. Psychopathol. 2014;20:223–243.

[9] Courvoisie H., Labellarte M.J., Riddle M.A. Psychosis in children: Diagnosis and treatment. Dialog. Clin. Neurosci. 2001;3:79–92. doi: 10.31887/DCNS.2001.3.2/hcourvoisie. - DOI - PMC - PubMed

[10] Courvoisie H., Labellarte M.J., Riddle M.A. Psychosis in children: Diagnosis and treatment. Dialog. Clin. Neurosci. 2001;3:79–92. doi: 10.31887/DCNS.2001.3.2/hcourvoisie. - DOI - PMC - PubMed

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The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study

Affiliations

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study

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Conflict of interest statement

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Abstract

Conflict of interest statement

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