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Impact of the CYP2D6 phenotype on hyperprolactinemia development as an adverse event of treatment with atypical antipsychotic agents in pediatric patients

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Abstract

Background

Treatment with atypical antipsychotics is today the election therapy for different types of psychosis, but there is a high incidence of endocrine and metabolic disturbances. One of the major enzymes involved in the metabolism of antipsychotics is CYP2D6. Depending on the existing CYP2D6 alleles, the metabolic capacity of the enzyme may vary from very low to very high, so that patients can be grouped into four phenotypic groups: slow, intermediate, extensive (normal), and fast metabolizers.

Aim of the study

The aim of the study is to find a relationship between the individual intervariability of CYP2D6 and the incidence of hyperprolactinemia as side effect of atypical antipsychotics.

Results

A total of 81 patients with schizophrenia or bipolar disorders, median age 15.74 ± 4 years, were enrolled in the study and prescribed the following atypical antipsychotics: risperidone, aripiprazole, and olanzapine. They were evaluated at 6, 12, and 18 months after the initiation of treatment. Using the TaqMan Genotyping Assay, it has been identified the presence of the CYP2D6*4 allele in 28 patients, representing 34.56% of the total of 81 patients in the study, and CYP2D6*3 allele was identified in 15 patients and the presence of CYP2D6*41 to 11 patients. The allele CYP2D6*5 has not been present to the study patients. The study group has 44 patients which are extensive metabolizers (54%), 34 intermediate metabolizers (42%), and 3 poor (slow) metabolizers (4%).

Conclusions

For the slow and intermediate metabolizers, atypical antipsychotics determined a significant increase of prolactinemia with high risk of adverse events.

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Acknowledgments

We thank Arshad Makhdum, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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Author notes

  1. Raluca Grădinaru and Nicoleta Andreescu contributed equally and thus share first authorship.

Authors and Affiliations

  1. Discipline of Medical Genetics, Department of Microscopic Morphology, Victor Babeş University of Medicine and Pharmacy Timișoara, Timișoara, Romania

    Raluca Grădinaru, Nicoleta Andreescu & Maria Puiu

  2. Discipline of Pedopsychiatry, Department of Neurosciences, Victor Babeş University of Medicine and Pharmacy Timișoara, Timișoara, Romania

    Laura Nussbaum

  3. Discipline of Pharmacology-Clinical Pharmacy, Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy Timișoara, Timișoara, Romania

    Liana Suciu

Authors
  1. Raluca Grădinaru
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  2. Nicoleta Andreescu
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  3. Laura Nussbaum
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  4. Liana Suciu
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  5. Maria Puiu
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Corresponding author

Correspondence to Liana Suciu.

Ethics declarations

The study protocol was approved by the Ethics Committee of Victor Babeș University of Medicine and Pharmacy Timișoara (Timișoara, Romania). For patients under 18 years of age, written informed consent was provided by parents or legal guardians.

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The authors declare that they have no conflict of interest.

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Grădinaru, R., Andreescu, N., Nussbaum, L. et al. Impact of the CYP2D6 phenotype on hyperprolactinemia development as an adverse event of treatment with atypical antipsychotic agents in pediatric patients. Ir J Med Sci 188, 1417–1422 (2019). https://doi.org/10.1007/s11845-019-01985-x

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  • DOI: https://doi.org/10.1007/s11845-019-01985-x

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