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Antipsychotic pharmacogenetics

Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Kamini Vasudev, Yun-Hee Choi, Ross Norman, Richard B Kim, Ute I Schwarz
OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine. METHOD: Genetic variants of relevance to clozapine metabolism, clearance, and response were assessed through targeted genotyping of cytochrome P450 enzymes CYP1A2 and CYP2C19, the efflux transporter ABCB1, the serotonin receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR)...
September 28, 2016: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Raymond R MacNeil, Daniel J Müller
The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels...
July 2016: Molecular Neuropsychiatry
Trehani M Fonseka, Daniel J Müller, Sidney H Kennedy
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation...
May 2016: Molecular Neuropsychiatry
Murray G Tucker, Sebastian Kekulawala, Michelle Kent, Sam Mostafa, Richard Harvey
BACKGROUND: The high prevalence of comorbid illicit drug use in persons with chronic psychotic illness represents a strong determinant of psychotic relapse and rehospitalization. Epidemiological studies indicate changing patterns of illicit drug use in Australia, which are concerning because of increased use of crystal methamphetamine, also known as "ice." An important complication of habitual use of crystal methamphetamine is the development of a dose-dependent acute psychotic reaction...
2016: Journal of Medical Case Reports
Javier Labad, Lourdes Martorell, Elena Huerta-Ramos, Jesús Cobo, Elisabet Vilella, Elena Rubio-Abadal, Gemma Garcia-Pares, Marta Creus, Cristian Núñez, Laura Ortega, Eva Miquel, Judith Usall
Several double-blind clinical trials have reported improvement in positive, negative and cognitive symptoms of schizophrenia with raloxifene, a selective receptor estrogen modulator. However, there are some inconsistencies in replicating findings between studies of different countries. The failure to replicate these findings may result from genetic factors that could explain some of the variability in the treatment response. However, pharmacogenetic studies exploring this topic in women with schizophrenia are lacking...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
F M Daray, D Rodante, L G Carosella, M E Silva, M Martínez, M V Fernández Busch, D F Faccone, R P Rothlin, P C Maffía
Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated...
July 14, 2016: Pharmacopsychiatry
Vanessa Gonzalez-Covarrubias, José Jaime Martínez-Magaña, Regina Coronado-Sosa, Beatriz Villegas-Torres, Alma D Genis-Mendoza, Pablo Canales-Herrerias, Humberto Nicolini, Xavier Soberón
PURPOSE: Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its association with drug efficacy in individuals receiving either anticoagulants or antipsychotic drugs. METHODS: Natives from three different states and Mestizo patients receiving acenocoumarol or antipsychotics were genotyped using the DMET microarray (Affymetrix)...
November 2016: Pharmaceutical Research
Itaru Miura, Jian-Ping Zhang, Katsuhiko Hagi, Todd Lencz, John M Kane, Hirooki Yabe, Anil K Malhotra, Christoph U Correll
BACKGROUND: Although dopamine D2 receptor antagonists lead to dose-dependent prolactin (PRL) elevations proportionate to their D2 affinity, considerable inter-individual differences exist. We conducted a meta-analytic review of associations between genetic variations in the dopamine D2 receptor gene (DRD2) and PRL levels in antipsychotic-treated subjects. METHODS: Systematic literature search (5/8/2015) was performed to find published studies of pharmacogenetic associations between two DRD2 variants, Taq1A (rs1800497) and -141C Ins/Del (rs1799732), and PRL levels during antipsychotic treatment (excluding aripiprazole)...
October 2016: Psychoneuroendocrinology
S Mas, P Gassó, A Lafuente, M Bioque, A Lobo, A Gonzàlez-Pinto, M S Olmeda, I Corripio, A Llerena, B Cabrera, J Saiz-Ruiz, M Bernardo
This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis...
October 2016: Pharmacogenomics Journal
J P Schacht
The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA...
October 2016: Pharmacogenomics Journal
Jian-Ping Zhang, Todd Lencz, Ryan X Zhang, Masahiro Nitta, Lawrence Maayan, Majnu John, Delbert G Robinson, W Wolfgang Fleischhacker, Rene S Kahn, Roel A Ophoff, John M Kane, Anil K Malhotra, Christoph U Correll
Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome)...
November 2016: Schizophrenia Bulletin
Stefano Porcelli, Beatrice Balzarro, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Chi-Un Pae, Alessandro Serretti
BACKGROUND: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. METHODS: Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the x03C7;2 statistics...
2016: Neuropsychobiology
E Sacchetti, C Magri, A Minelli, P Valsecchi, M Traversa, S Calza, A Vita, M Gennarelli
The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia...
February 9, 2016: Pharmacogenomics Journal
Florence Gressier, Stefano Porcelli, Raffaella Calati, Alessandro Serretti
Clozapine (CLZ) is the prototype atypical antipsychotic and it has many advantages over other antipsychotic drugs. Several data suggest that both CLZ response and induced weight gain are strongly determined by genetic variability. However, results remain mainly inconclusive. We aim to review the literature data about pharmacogenetics studies on CLZ efficacy, focusing on pharmacodynamic genes. Further, we performed meta-analyses on response when at least three studies for each polymorphism were available. Sensitivity analyses were conducted on Caucasian population when feasible...
February 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Nuwan C Hettige, Gustavo H F de Moraes, James L Kennedy, Vincenzo De Luca
AIM: In order to administer antipsychotic medication with the most beneficial outcome, the appropriate drug and dose needs to be identified. Though often not considered in pharmacogenetic studies, dosage plays an important role in treatment outcome. This study set out to analyze the association between 109 SNPs and antipsychotic dosage among schizophrenia patients. In a previous study, we tested 134 SNPs in regards to antipsychotic dosage. In the current study, we tested additional markers in the same candidate genes that we investigated in the previous study to confirm our previous findings...
February 2016: Pharmacogenomics
A E Gareeva, K O Kinyasheva, D Yu Galaktionova, E T Sabirov, R G Valinourov, A V Chudinov, A S Zasedatelev, T V Nasedkina, E K Khusnutdinova
Antipsychotics are the main drugs for the treatment of severe mental illness--schizophrenia affects about 1% of the population. The mechanism of action of neuroleptics is still up to the end. Several studies in the field of pharmacogenetics confirm enourmous influence of several neurotransmitter systems in the brain on the efficiency and the development of side effects. In this paper, we analyzed the association of nine polymorphic variants of five genes of dopaminergic and serotonergic systems DRD4, HTR2A, TPH1, SLC18A1, COMT in Russian and Tatars patients living in the Republic of Bashkortostan (RB) with the efficiency of a typical antipsychotic haloperidol on the scale of positive and negative systems of PANSS...
November 2015: Molekuliarnaia Biologiia
Georgia Ragia, Marja-Liisa Dahl, Vangelis G Manolopoulos
BACKGROUND: The contribution of the CYP3A5 enzyme to the metabolism of clinically used drugs has been established only for a few CYP3A substrates, such as the immunosuppressant tacrolimus, while for drugs used in the field of psychiatry its role is still vague. METHODS: We herein discuss all published data on the contribution of CYP3A5 and its polymorphisms to the metabolism of antipsychotics and antidepressants that are known to be metabolized by CYP3A enzymes, as well as of carbamazepine, an antiepileptic drug used as mood stabilizer...
2016: Current Drug Metabolism
Sergi Mas, Patricia Gassó, Amelia Lafuente
Pharmacogenetics has been driven by a candidate gene approach. The disadvantage of this approach is that is limited by our current understanding of the mechanisms by which drugs act. Gene expression could help to elucidate the molecular signatures of antipsychotic treatments searching for dysregulated molecular pathways and the relationships between gene products, especially protein-protein interactions. To embrace the complexity of drug response, machine learning methods could help to identify gene-gene interactions and develop pharmacogenetic predictors of drug response...
November 2015: Pharmacogenomics
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