THE COMBINED EFFECT OF CYP2D6 AND DRD2 Taq1A POLYMORPHISMS ON THE ANTIPSYCHOTICS DAILY DOSES AND HOSPITAL STAY DURATION IN SCHIZOPHRENIA INPATIENTS (OBSERVATIONAL NATURALISTIC STUDY)

Курылев, А. А.; Brodyansky, V. M.; Andreev, B. V.; Кибитов, А.О.; Лиманкин, О. В.; Mosolov, S.

doi:10.24869/psyd.2018.157

Cited by 13 publications

(6 citation statements)

References 7 publications

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“…Interestingly, CYP2D6 metabolic activity affects mean antipsychotics daily dose only in the presence of DRD2 Taq1A polymorphic allele. Subpopulation of schizophrenia inpatients with altered CYP2D6 activity (poor and ultra rapid metabolizers) and when carriers of Taq1A polymorphisms needs special attention of clinicians in aligning of antipsychotic treatment (Kurylev et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

CLASH-VLT: a full dynamical reconstruction of the mass profile of Abell S1063 from 1 kpc out to the virial radius

Sartoris

Biviano

Rosati

et al. 2020

A&A

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Context. The shape of the mass density profiles of cosmological halos informs us of the nature of dark matter (DM) and DM-baryons interactions. Previous estimates of the inner slope of the mass density profiles of clusters of galaxies are in opposition to predictions derived from numerical simulations of cold dark matter (CDM). Aims. We determine the inner slope of the DM density profile of a massive cluster of galaxies, Abell S1063 (RXC J2248.7−4431) at z = 0.35, with a dynamical analysis based on an extensive spectroscopic campaign carried out with the VIMOS and MUSE spectrographs at the ESO VLT. This new data set provides an unprecedented sample of 1234 spectroscopic members, 104 of which are located in the cluster core (R ≲ 200 kpc), extracted from the MUSE integral field spectroscopy. The latter also allows the stellar velocity dispersion profile of the brightest cluster galaxy (BCG) to be measured out to 40 kpc. Methods. We used an upgraded version of the MAMPOSSt technique to perform a joint maximum likelihood fit to the velocity dispersion profile of the BCG and to the velocity distribution of cluster member galaxies over a radial range from 1 kpc to the virial radius (r200 ≈ 2.7 Mpc). Results. We find a value of γDM = 0.99 ± 0.04 for the inner logarithmic slope of the DM density profile after marginalizing over all the other parameters of the mass and velocity anisotropy models. Moreover, the newly determined dynamical mass profile is found to be in excellent agreement with the mass density profiles obtained from the independent X-ray hydrostatic analysis based on deep Chandra data, as well as the strong and weak lensing analyses. Conclusions. Our value of the inner logarithmic slope of the DM density profile γDM is in very good agreement with predictions from cosmological CDM simulations. We will extend our analysis to more clusters in future works. If confirmed on a larger cluster sample, our result makes this DM model more appealing than alternative models.

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Section: Introductionmentioning

confidence: 99%

CLASH-VLT: a full dynamical reconstruction of the mass profile of Abell S1063 from 1 kpc out to the virial radius

Sartoris

Biviano

Rosati

et al. 2020

A&A

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“…These processes include transport across biological membranes, such as absorption and excretion, and metabolism. Individuals with greater metabolism may require higher doses, while those with lower metabolic rates might be more prone to the drugs' adverse effects and need dose reduction [3][4][5][6][7] . With all these variables potential predictors of drug response, which of them, or combination of, is the best predictor of clinical endpoints, if at all.…”

Section: Introductionmentioning

confidence: 99%

The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

Cendrós¹,

Arranz²,

Torra³

et al. 2020

JTGG

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Aim: Genetic variants on metabolic and transport enzymes are good candidates to explain inter-individual differences in response to antipsychotics. The aim of this study is to evaluate and compare the influence of the CYP2D6 , CYPC19, CYP1A2 and ABCB1 variants on plasma levels, treatment response and side effects of antipsychotics. Methods: Twenty polymorphisms in selected genes were genotyped in 318 patients diagnosed with schizophrenia, schizoaffective or delusional disorder treated with antipsychotics (clozapine, olanzapine, paliperidone, risperidone, aripiprazole and quetiapine). Plasma drug levels were determined after 6 weeks of treatment. The Positive and Negative Symptoms Scale (PANSS) and UKU scale of side effects were recorded at baseline and after 12 weeks of treatment. The effect of gene variants on plasma drug levels, treatment response and adverse effects were examined by multinomial regression. Results: CYP1A2 was found to be associated with psychic side effects (P = 0.02), with variants predicting higher enzyme activity associated with lower adverse effects, and was the strongest predictor for this adverse effect of all the studied factors. Functional variants in CYP genes were associated with plasma level differences, with higher activity variants associated with lower plasma levels. No association with improvement of the condition, as measured by the PANSS score, was found in this study. Conclusion: The results suggest that increased CYP1A2 activity protects against psychic side effects. Few studies have evaluated the impact of genetic factors on treatment response or side effects, and only in relation to a selection of adverse reactions. These results are a step towards better understanding of the factors behind the different aspects of clinical outcomes, such as various adverse effects.

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“…A study performed in patients with psychiatric conditions taking drugs not recommended based on genetic information showed that they have 69% more total health care visits, 67% more medical visits and three times more medical absence days compared to patients taking drugs recommended based on their genotypes [ 122 ]. Another study associated CYP2D6 PMs and UMs to longer hospital stay duration compared to EMs [ 123 ]. In 2013, Herbild et al [ 124 ] demonstrated cost-effectiveness of preemptive CYP2D6 or CYP2C19 genotyping in patients with schizophrenia.…”

Section: Pharmacokinetics/pharmacogenetics Implementationmentioning

confidence: 99%

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

et al. 2021

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Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of life.

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THE COMBINED EFFECT OF CYP2D6 AND DRD2 Taq1A POLYMORPHISMS ON THE ANTIPSYCHOTICS DAILY DOSES AND HOSPITAL STAY DURATION IN SCHIZOPHRENIA INPATIENTS (OBSERVATIONAL NATURALISTIC STUDY)

Cited by 13 publications

References 7 publications

CLASH-VLT: a full dynamical reconstruction of the mass profile of Abell S1063 from 1 kpc out to the virial radius

CLASH-VLT: a full dynamical reconstruction of the mass profile of Abell S1063 from 1 kpc out to the virial radius

The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

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