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Review
. 2009;11(4):405-15.
doi: 10.31887/DCNS.2009.11.4/tlencz.

Pharmacogenetics of antipsychotic-induced side effects

Todd Lencz  1 , Anil K Malhotra
Affiliations
Review

Pharmacogenetics of antipsychotic-induced side effects

Todd Lencz et al. Dialogues Clin Neurosci. 2009.

Abstract
in English, Spanish, French

Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.

Actualmente los fármacos antipsicóticos (FAP) disponibles conllevan, con una alta y significativa aunque variable probabilidad, efectos secundarios neurológicos y metabólicos. Las aproximaciones farmacogenéticas ofrecen la posibilidad de identificar biomarcadores específicos para el paciente para predecir el riesgo de estos efectos secundarios. A la fecha, multiples estudios ban convergido en dar sustento a unos pocos polimorfismos de nucleotidos simples (SNPs) de un pequeño grupo de genes. El foco primario ha estado en los SNPs de los genes de los receptores de dopamina y serotonina; estudios de meta-análisis han demostrado una evidencia convincente para el efecto de los genes de los receptores de dopamina D2 y D3 (RDD2 y RDD3) en el riesgo de disquinesia tardía (DT) y para un efecto de variación del gen del receptor 5HT2C (R5HT2C) en la probabilidad de aumento de peso inducido por los FAP. Sin embargo, la magnitud del efecto parece ser modesta y las consideraciones farmacoeconómicas no se han estudiado suficientemente, por lo que la aplicación clínica en este momento es limitada. En este artículo se revisan los efectos de estos y otros genes en los riesgos de DT, efectos secundarios extrapiramidales, hiperprolactinemia y aumento de peso.

Les médicaments antipsychotiques disponibles actuellement sont significativemeni responsables, bien que de façon très variable, d'effets secondaires métaboliques et neurologiques. La pharmacogénétique permet d'identifier des biomarqueurs spécifiques des patients permettant de prédire le risque de survenue de ces effets indésirables. À ce jour, un petit nombre de polymorphismes de nucleotide simple (single nucleotide polymorphism ou SNP) issus d'une poignée de gènes, a été identifié au cours de plusieurs études. Les SNP des gènes du récepteur à la dopamine et à la sêrotonine ont été les premiers à être étudiés: des metaanalyses convaincantes ont montré une implication des gènes DRD2 et DRD3 (récepteur à la dopamine D2 et D3) dans le risque de dyskinésies tardives (DT) et celle d'une variation du gène du récepteur HT2C (5-HTR2C) dans la prise de poids due aux antipsychotiques. L'importance de ces effets semble néanmoins modeste et, les considérations pharmacoéconomiques étant insuffisamment étudiées, les applications cliniques restent aujourd'hui limitées. Cet article analyse les effets de ces gènes ainsi que d'autres sur le risque de DT, d'effets extrapyramidaux, d'hyperprolactinémie et de prise de poids.

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Figures

Figure 1.
Figure 1.. Location of the Taq1A polymorphism in the context of ANKK1 and DRD2 at chromosome 11q22. Red triangles represent areas of high linkage equilibrium (D').
See this image and copyright information in PMC

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