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Antipsychotic pharmacogenetics

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https://www.readbyqxmd.com/read/28782490/unmet-needs-in-schizophrenia
#1
Maurizio Pompili, Gloria Giordano, Mario Luciano, Valeria Del Vecchio, Gianluca Serafini, Gaia Sampogna, Denise Erbuto, Peter Falkai, Andrea Fiorillo
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
August 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28758583/new-trends-in-the-treatment-of-schizophrenia
#2
Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28673279/pharmacogenetic-evaluation-to-assess-breakthrough-psychosis-with-aripiprazole-long-acting-injection-a-case-report
#3
Seenae Eum, Mark E Schneiderhan, Jacob T Brown, Adam M Lee, Jeffrey R Bishop
BACKGROUND: Given the complex nature of symptom presentation and medication regimens, psychiatric clinics may benefit from additional tools to personalize treatments. Utilizing pharmacogenetic information may be helpful in assessing unique responses to therapy. We report herein a case of wearing-off phenomena during treatment with aripiprazole long-acting injectable (LAI) and a proof of concept strategy of how pharmacogenetic information may be used to assess possible genetic factors and also hypothesize potential mechanisms for further study...
July 3, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#4
REVIEW
Frederick C Nucifora, Marina Mihaljevic, Brian J Lee, Akira Sawa
Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28539103/possible-oxcarbazepine-inductive-effects-on-aripiprazole-metabolism-a-case-report
#5
Ian R McGrane, Joshua G Loveland, Jose de Leon
Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28389049/intuitive-pharmacogenetic-dosing-of-risperidone-according-to-cyp2d6-phenotype-extrapolated-from-genotype-in-a-cohort-of-first-episode-psychosis-patients
#6
Sergi Mas, Patricia Gassó, Mercé Torra, Miquel Bioque, Antonio Lobo, Ana González-Pinto, Maria Soledad Olmeda, Iluminada Corripio, Eduard Vieta, Josefina Castro-Fornieles, Roberto Rodriguez-Jimenez, Julio Bobes, Judith Usall, Adrián Llerena, Jerónimo Saiz-Ruiz, Miguel Bernardo, Amalia Lafuente, PEPs Group
Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an "intuitive pharmacogenetic" process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes...
July 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28277565/pharmacogenetic-analysis-of-functional-glutamate-system-gene-variants-and-clinical-response-to-clozapine
#7
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy
Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27956478/pharmacological-treatment-of-refugees-with-trauma-related-disorders-what-do-we-know-today
#8
REVIEW
Charlotte Sonne, Jessica Carlsson, Per Bech, Erik Lykke Mortensen
There is a dearth of evidence on the effectiveness of pharmacological treatment for refugees with trauma-related disorders. The present paper provides an overview of available literature on the subject and discusses the transferability of results from studies on other groups of patients with post traumatic stress disorder (PTSD). We conducted a systematic review of published treatment outcome studies on PTSD and depression among refugees. Fifteen studies were identified and reviewed. Most studies focused on the use of antidepressants...
December 12, 2016: Transcultural Psychiatry
https://www.readbyqxmd.com/read/27875318/1846g-a-polymorphism-of-cyp2d6-gene-and-extrapyramidal-side-effects-during-antipsychotic-therapy-among-russians-and-tatars-a-pilot-study
#9
Dmitriy A Sychev, Irina S Burashnikova, Ruslan E Kazakov
BACKGROUND: Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups. METHODS: We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. RESULTS: Heterozygous 1846GA genotype frequency among Tatars was lower (23...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27757066/pharmacogenetic-tests-for-antipsychotic-medications-clinical-implications-and-considerations
#10
Seenae Eum, Adam M Lee, Jeffrey R Bishop
Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients...
September 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/27752976/pharmacogenomics-and-pharmacogenetics-for-the-intensive-care-unit-a-narrative-review
#11
REVIEW
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...
January 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/27681143/genetic-determinants-of-clozapine-induced-metabolic-side-effects
#12
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)...
February 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/27606321/genetics-of-common-antipsychotic-induced-adverse-effects
#13
REVIEW
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
https://www.readbyqxmd.com/read/27606316/inflammatory-cytokines-and-antipsychotic-induced-weight-gain-review-and-clinical-implications
#14
REVIEW
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
https://www.readbyqxmd.com/read/27599617/polysubstance-induced-relapse-of-schizoaffective-disorder-refractory-to-high-dose-antipsychotic-medications-a-case-report
#15
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...
September 6, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27546373/pharmacogenetic-study-of-the-effects-of-raloxifene-on-negative-symptoms-of-postmenopausal-women-with-schizophrenia-a-double-blind-randomized-placebo-controlled-trial
#16
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
https://www.readbyqxmd.com/read/27469238/pharmacogenetics-of-tardive-dyskinesia-an-updated-review-of-the-literature
#17
REVIEW
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
https://www.readbyqxmd.com/read/27414739/-759c-t-polymorphism-of-the-htr2c-gene-is-associated-with-second-generation-antipsychotic-induced-weight-gain-in-female-patients-with-schizophrenia
#18
Federico Manuel Daray, Demián Rodante, Laura G Carosella, María Elena Silva, Melina Martínez, María V Fernández Busch, Diego F Faccone, Rodolfo P Rothlin, Paulo 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...
January 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/27387170/exploring-variation-in-known-pharmacogenetic-variants-and-its-association-with-drug-response-in-different-mexican-populations
#19
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
https://www.readbyqxmd.com/read/27333159/variants-in-the-drd2-locus-and-antipsychotic-related-prolactin-levels-a-meta-analysis
#20
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
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