The effect of the Taq1A variant in the dopamine D2 receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys

Roke, Yvette; Harten, Peter N. van; Franke, Barbara; Galesloot, Tessel E.; Boot, Annemieke M.; Buitelaar, Jan K.

doi:10.1097/fpc.0b013e3283647c33

Cited by 34 publications

(42 citation statements)

References 42 publications

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“…A study by Roke et al [25] aimed to better understand the hyperprolactinemia associated with risperidone use, which affects 50 % of children on long-term treatment. Based on the role of dopamine 2 antagonism and association between the A1 allele of the dopamine D2 receptor (DRD2) Taq1A polymorphism in adults, the authors investigated whether variation in the DRD2 gene may modify the effects of risperidone on prolactin levels.…”

Section: Atypical Antipsychoticsmentioning

confidence: 99%

Pharmacogenomic Medicine in Autism: Challenges and Opportunities

2014

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Autism spectrum disorder (ASD) affects 1 in 68 children in the US and is distinguished by core deficits in social interactions. Developing pharmacologic treatments for ASD is complicated by clinical and genetic heterogeneity. Although pharmacological treatments have not been shown to be effective in treating the core symptoms of ASD (i.e., social deficits), there is evidence that the burden of emotional and behavioral problems can be reduced with pharmacotherapy. Numerous randomized clinical trials of treatments for the core ASD deficits have been conducted; however, most have provided inconclusive results due to the substantial variation in treatment response. Variation also exists in the considerable metabolic side effects of many of the current treatments. Some of this variation may be explained by differences in the underlying genetic pathways. Exploiting the link between genetic heterogeneity and clinical variation associated with behavioral problems may provide an opportunity for targeted treatment of ASD. In this review, we summarize the recent findings from pharmacogenomics studies of ASD and suggest further how understanding how genetic liability modifies the effect of drugs may present an opportunity to address the challenges of personalized medicine in autism.

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Section: Atypical Antipsychoticsmentioning

confidence: 99%

Pharmacogenomic Medicine in Autism: Challenges and Opportunities

2014

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“…It should also be noted that lower doses could also cause serious adverse events [29]. It is important to keep in mind that hyperprolactinaemia may be present without these adverse events [13,30,31].…”

Section: Discussionmentioning

confidence: 99%

“…Elevation of prolactin concentration corresponds to dopamine D2 receptor blockade [9,10]. Most studies report that children and adolescents treated with risperidone have 38-50% incidence of hyperprolactinaemia [4,[11][12][13][14][15][16].Early studies reported adverse effects associated with prolactin elevation because hyperprolactinaemia is one of the most common endocrinological disorders of the hypothalamic-pituitary axis [8]. Hyperprolactinaemia in female patients can result in amenorrhoea, galactorrhoea, anovulation and irregular menses, and in male patients, it can lead to azoospermia, impotence, gynaecomastia and galactorrhoea [17].…”

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confidence: 99%

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9‐Hydroxyrisperidone‐Induced Hyperprolactinaemia in Thai Children and Adolescents with Autism Spectrum Disorder

Ngamsamut

Hongkaew

Vanwong

et al. 2016

Basic Clin Pharma Tox

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Although our previous study revealed an association between prolactin level and risperidone dosage, data regarding the plasma concentration of risperidone are lacking. Therefore, this study aimed to investigate the association between plasma drug concentrations of risperidone, 9-hydroxyrisperidone and serum prolactin level in Thai children and adolescents with autism spectrum disorder (ASD). The individuals for this study were 103 children and adolescents with ASD (90 males and 13 females). In the 12th hour after the last risperidone dose, blood samples were collected for analysis. Serum prolactin, plasma risperidone and 9-hydroxyrisperidone levels were measured. Patients' clinical data were collected from medical records -age, weight, height, body mass index, dose of risperidone and duration of treatment. Serum prolactin level was significantly positively correlated with plasma 9-hydroxyrisperidone level (r s = 0.355, p < 0.001). The median concentration of 9-hydroxyrisperidone in individuals with hyperprolactinaemia (7.59 ng/ml; IQR 4.86-15.55) was significantly higher than non-hyperprolactinaemic individuals (5.18 ng/ml; IQR 2.10-8.99) after risperidone treatment (p = 0.006). By multivariate analysis, high prolactin level was correlated to high 9-hydroxyrisperidone level (p = 0.010). The results of this study showed that serum prolactin levels, especially in autistic individuals with hyperprolactinaemia during risperidone treatment, were significantly correlated with the level of 9-hydroxyrisperidone. These results suggest that hyperprolactinaemia may develop during risperidone treatment.Risperidone is the most used pharmacotherapy for irritability in autism spectrum disorder (ASD) and is currently approved by the US Food and Drug Administration (FDA) [1,2]. Moreover, risperidone has been demonstrated to have moderate and clinically significant benefits [3] in treatment of behavioural disturbances, including attention deficit hyperactivity disorder, anxiety disorders and obsessive-compulsive disorder [4].Primarily, risperidone is metabolized in the liver by the CYP2D6 enzyme. The main metabolite of risperidone, 9-hydroxyrisperidone, has similar pharmacological activity as its parent compound, and the serum concentration of the active moiety is thus the sum of the serum concentrations of risperidone and 9-hydroxyrisperidone [5]. Risperidone has high susceptibility to elevate prolactin levels compared with other atypical antipsychotic therapies [6] because these medications are known to have a potent antagonistic activity against serotonin 5HT2, but mild dopamine D2 antagonistic activity [7,8]. Elevation of prolactin concentration corresponds to dopamine D2 receptor blockade [9,10]. Most studies report that children and adolescents treated with risperidone have 38-50% incidence of hyperprolactinaemia [4,[11][12][13][14][15][16].Early studies reported adverse effects associated with prolactin elevation because hyperprolactinaemia is one of the most common endocrinological disorders of the hypothalamic-...

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“…A well-known side effect associated with risperidone is the elevation of prolactin levels. 1 This elevation occurs because risperidone antagonizes D2 receptors on lactotroph cells of the anterior pituitary gland, which serves a main inhibitory role in prolactin secretion. Risperidone causes higher levels of prolactin elevation compared to other atypical antipsychotics.…”

mentioning

confidence: 99%