Risperidone plasma levels, clinical response and side–effects

Riedel, Michael; Schwarz, Markus J.; Strassnig, Martin; Spellmann, Ilja; Müller-Arends, A; Weber, Kim S.C.; Zach, J.; Müller, Norbert; Möller, Hans‐Jürgen

doi:10.1007/s00406-004-0556-4

Cited by 116 publications

(90 citation statements)

References 48 publications

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“…In recent studies, it was observed that CYP2D6 did not predict response to risperidone, but predicted metabolic ratios and side effects. [62][63][64] No association was found between CYP2D6 PM variants and clozapine response. 65 However, small adjustments of therapeutic doses of clozapine are recommended according to CYP2D6 genotypes, suggesting that these enzymes are only minor pathways for clozapine metabolism.…”

Section: Pharmacokinetic Factorsmentioning

confidence: 97%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

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Section: Pharmacokinetic Factorsmentioning

confidence: 97%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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“…Ten studies were interested in the relationship between efficacy and CYP2D6 [90][91][92][93][95][96][97][98][99] or CYP1A2. 94 A wide variety of outcomes were considered across the studies but no two studies measured outcomes in exactly the same way.…”

Section: Clinical Validitymentioning

confidence: 99%

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

et al. 2010

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There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and metaanalyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.

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“…This gene is considered to be highly polymorphic. We discussed four genetic variants involved in differences in treatment responses in various populations ( • PMs tend to accumulate higher drug levels in blood, and theoretically, require lower doses to achieve therapeutic effects (Kakihara et al [21], n=136; Riedel et al [22], n=82)…”

Section: Cyp2d6mentioning

confidence: 99%

“…Thus, there is a lower dose requirement to attain a therapeutic effect for PMs [21,22]. In contrast, ultra rapid metabolizers (UMs) are needed in higher doses to produce a therapeutic effect [23].…”

Section: Cyp2d6mentioning

confidence: 99%

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

Cho¹,

Contreras²,

Garza³

et al. 2017

Bipolar Disord

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Objective: Schizophrenia, a neuropsychiatric disorder, is known to be neurodevelopmentally progressive. Due to the extensive interindividual variability found in the responses of patients, management of schizophrenia has proven to be challenging. This interindividual variability to treatment could be justified by the variation of the enzymes in charge of metabolizing medications, especially those associated with cytochrome P450. Since genetic factors influence the phenotypic responses to drugs, researchers are involved in identifying schizophrenic genetic factors, which could impact responses and severe effects for commonly known neuroleptic drugs known as pharmacogenetics. In order to predict drug response at the personal level, genetic variants that determine drug effects need to be identified. Methods:We have chosen to investigate gene targets for risperidone and clozapine, two commonly administered drugs for the treatment of schizophrenia. The aim of this review is to contribute in the understanding of genetic influences on drug responses of risperidone and clozapine in schizophrenia. We reviewed original primary research articles, meta-analysis, and review publications on drug and gene interaction on the treatment of schizophrenia. Our main findings focused on schizophrenia, pharmacogenetics and cytochrome P450. Results and conclusion:After filtering our results to human species and English language, a total of 45 scientific articles were used for this review. A promising direction for future research in schizophrenia treatment lies behind the identification of the specific genetic contributors that affect drug response.

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Risperidone plasma levels, clinical response and side–effects

Cited by 116 publications

References 48 publications

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

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