scholarly journals Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders

2021 ◽  
Vol 10 (18) ◽  
pp. 4275
Author(s):  
Lorena Carrascal-Laso ◽  
María Isidoro-García ◽  
Ignacio Ramos-Gallego ◽  
Manuel A. Franco-Martín
Keyword(s):  
Second Generation ◽  
Psychotic Disorders ◽  
State Of The Art ◽  
Current Knowledge ◽  
Pharmacokinetic Parameters ◽  
Antipsychotic Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Second Generation Antipsychotics ◽  
Second Generation Antipsychotic

Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.

Atypical (second generation) antipsychotic treatment response in very late-onset schizophrenia-like psychosis

2010 ◽  
Vol 23 (5) ◽  
pp. 742-748 ◽  
Author(s):  
Jamie Scott ◽  
Blaine S. Greenwald ◽  
Elisse Kramer ◽  
Mitchell Shuwall
Keyword(s):  
Treatment Response ◽  
Atypical Antipsychotic ◽  
Second Generation ◽  
Psychotic Disorders ◽  
Age Of Onset ◽  
Late Onset ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Positive Treatment ◽  
Second Generation Antipsychotic

ABSTRACTIntroduction: Symptom amelioration in older patients with very late onset schizophrenia-like psychosis (VLOSLP) is often difficult, with limited psychotropic response reports yielding variable findings. Information about atypical (second generation) antipsychotic use in this population is scant.Methods: A consecutive sample of geriatric psychiatry outpatients and inpatients with psychotic disorders were retrospectively identified over a 31-month period based on systematic information abstraction from an electronic medical record (e-record). After exclusion criteria were applied, 8/138 outpatients and 13/362 inpatients met inclusion criteria for VLOSLP and had been naturalistically treated with an atypical antipsychotic during hospitalization or nine months of outpatient care. Mandatorily completed e-record standardized symptom severity response ratings were converted into positive treatment response thresholds.Results: 38% of outpatients and 77% of inpatients (mean age = 76 years for both groups; mean age of onset of psychosis = 70 years for outpatients and 74 years for inpatients) met criteria for positive treatment response to an atypical antipsychotic (either aripiprazole, olanzapine, quetiapine, or risperidone) with sign/symptom amelioration, rather than eradication.Conclusions: Various atypical antipsychotics at geriatric doses yielded a positive treatment response in nearly two-thirds of VLOSLP patients. Patients with less chronic, more severe symptoms responded at a higher rate. Prospective, double-blind, placebo-controlled trials with representative subject samples are needed to validate these preliminary findings.

scholarly journals First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: Systematic review and meta-analysis

2008 ◽  
Vol 192 (6) ◽  
pp. 406-411 ◽  
Author(s):  
M. Smith ◽  
D. Hopkins ◽  
R. C. Peveler ◽  
R. I. G. Holt ◽  
M. Woodward ◽  
...  
Keyword(s):  
Systematic Review ◽  
First Generation ◽  
Second Generation ◽  
Psychotic Disorders ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Antipsychotic Treatment ◽  
Cross Sectional ◽  
Increased Risk ◽  
Second Generation Antipsychotics

BackgroundThe increased prevalence of diabetes in schizophrenia is partly attributed to antipsychotic treatment, in particular second-generation antipsychotics, but the evidence has not been systematically reviewed.AimsSystematic review and meta-analysis comparing diabetes risk for different antipsychotics in people with schizophrenia.MethodWe searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were eligible for inclusion if the design was cross-sectional, case-control, cohort or a controlled trial in individuals with schizophrenia or related psychotic disorders, where second-generation antipsychotics (defined as clozapine, olanzapine, risperidone and quetiapine) were compared with first-generation antipsychotics and diabetes was an outcome. Data were pooled using random effects inverse variance weighted meta-analysis.ResultsOf the studies that met the inclusion criteria (n=14), 11 had sufficient data to include in the meta-analysis. Four of these were retrospective cohort studies. The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation v. first-generation antipsychotics was 1.32 (95% CI 1.15-1.51). There were insufficient data to include aripiprazole, ziprasidone and amisulpride in this analysis.ConclusionsThere is tentative evidence that the second-generation antipsychotics included in this study are associated with a small increased risk for diabetes compared with firstgeneration antipsychotics in people with schizophrenia. Methodological limitations were found in most studies, leading to heterogeneity and difficulty interpreting data. Regardless of type of antipsychotic, screening for diabetes in all people with schizophrenia should be routine.

Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated with Second-Generation Antipsychotic-Induced Weight Gain

2018 ◽  
Vol 52 (01) ◽  
pp. 16-23 ◽  
Author(s):  
Charlotte Schröder ◽  
Fabian Czerwensky ◽  
Stefan Leucht ◽  
Werner Steimer
Keyword(s):  
Weight Gain ◽  
Fat Mass ◽  
Second Generation ◽  
Nucleotide Polymorphisms ◽  
Fto Gene ◽  
Antipsychotic Therapy ◽  
A Value ◽  
Second Generation Antipsychotics ◽  
Study Population ◽  
Second Generation Antipsychotic

Abstract Introduction Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. Methods We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study. Results After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0.05). In a subpopulation without additional weight-inducing comedication (n=178), G-allele carriers of rs7185735 gained 3.4 times more weight (1.69 kg±3.1 kg, p=0.019) than AA genotypes (0.49 kg±3.1 kg). A-allele carriers of rs9939609 gained 3.1 times more weight (1.65 kg±3.1 kg, p=0.029) than TT genotypes (0.54 kg±3.2 kg). Discussion Our findings confirm the role of the FTO gene as a high-potential risk factor for obesity and indicate a value for predicting a weight gain induced by second-generation antipsychotics. Further, we detected an additive effect of FTO rs7185735 and MC4R rs17782313.

Antipsychotic utilisation and persistence in Australia: A nationwide 5-year study

2021 ◽  
pp. 000486742110516
Author(s):  
Mark Taylor ◽  
Dante Dangelo-Kemp ◽  
Dennis Liu ◽  
Steve Kisely ◽  
Simon Graham ◽  
...  
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Treatment Persistence ◽  
Persistence Time ◽  
Hazard Ratios ◽  
Second Generation Antipsychotics ◽  
Time In Treatment ◽  
Second Generation Antipsychotic ◽  
Long Acting ◽  
Subsequent Relapse

Objectives: To evaluate the utilisation and persistence of antipsychotics for the treatment of schizophrenia in Australia. Methods: A retrospective study using the Australian Pharmaceutical Benefits Scheme database of a representative 10% sample. All adults with schizophrenia who were dispensed three or more supplies of oral (including clozapine) or long-acting injectable antipsychotics between 1 June 2015 and 31 May 2020 were included. Persistence time in treatment was evaluated using survival analysis and Cox hazard ratios. Results: In all, 26,847 adults with schizophrenia were studied. Oral second-generation antipsychotics were more frequently dispensed than the other antipsychotic groups studied. Median treatment persistence times were 18.3 months for second-generation antipsychotic long-acting injectables, 10.7 months for oral second-generation antipsychotics and were significantly lower for both formulations of first-generation antipsychotics at 5.2 months (long-acting injectables) and 3.7 months (oral). The median persistence time for clozapine was significantly longer than all other antipsychotics groups. Conclusions: Oral second-generation antipsychotics and second-generation antipsychotic long-acting injectables accounted for over 75% and 13% of all antipsychotics in Australia, respectively. Concerns over medication adherence and subsequent relapse have not translated into increased long-acting injectable usage despite their significantly longer persistence. Clozapine, the single most ‘persistent’ antipsychotic, was only used in 9% of people, although up to a third of all cases are likely to be treatment-resistant. Our data suggest clinicians should give consideration to the earlier use of second-generation antipsychotic long-acting injectables and clozapine, to ameliorate prognosis in schizophrenia.

scholarly journals Treatment Response of Add-On Esketamine Nasal Spray in Resistant Major Depression in Relation to Add-On Second-Generation Antipsychotic Treatment

2020 ◽  
Vol 23 (7) ◽  
pp. 440-445 ◽  
Author(s):  
Markus Dold ◽  
Lucie Bartova ◽  
Siegfried Kasper
Keyword(s):  
Major Depressive Disorder ◽  
Confidence Interval ◽  
Depressive Disorder ◽  
Nasal Spray ◽  
Second Generation ◽  
Mean Difference ◽  
Inadequate Response ◽  
Major Depressive ◽  
Second Generation Antipsychotics ◽  
Second Generation Antipsychotic

Abstract In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference  = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.

Genetics of Schizophrenia and Bipolar Disorder

2017 ◽  
Author(s):  
Alexander Charney ◽  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

scholarly journals FUT2, Secretor Status and FUT3 Polymorphisms of Children with Acute Diarrhea Infected with Rotavirus and Norovirus in Brazil

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1084
Author(s):  
Marco André Loureiro Tonini ◽  
Débora Maria Pires Gonçalves Barreira ◽  
Luciana Bueno de Freitas Santolin ◽  
Lays Paula Bondi Volpini ◽  
José Paulo Gagliardi Leite ◽  
...  
Keyword(s):  
Acute Diarrhea ◽  
Current Knowledge ◽  
Host Susceptibility ◽  
High Rate ◽  
Southeastern Brazil ◽  
Blood Group Antigens ◽  
Nucleotide Polymorphisms ◽  
Symptomatic Infection ◽  
Single Nucleotide ◽  
Secretor Status

Host susceptibility according to human histo-blood group antigens (HBGAs) is widely known for norovirus infection, but is less described for rotavirus. Due to the variable HBGA polymorphism among populations, we aimed to evaluate the association between HBGA phenotypes (ABH, Lewis and secretor status) and susceptibility to rotavirus and norovirus symptomatic infection, and the polymorphisms of FUT2 and FUT3, of children from southeastern Brazil. Paired fecal-buccal specimens from 272 children with acute diarrhea were used to determine rotavirus/norovirus genotypes and HBGAs phenotypes/genotypes, respectively. Altogether, 100 (36.8%) children were infected with rotavirus and norovirus. The rotavirus P[8] genotype predominates (85.7%). Most of the noroviruses (93.8%) belonged to genogroup II (GII). GII.4 Sydney represented 76% (35/46) amongst five other genotypes. Rotavirus and noroviruses infected predominantly children with secretor status (97% and 98.5%, respectively). However, fewer rotavirus-infected children were Lewis-negative (8.6%) than the norovirus-infected ones (18.5%). FUT3 single nucleotide polymorphisms (SNP) occurred mostly at the T59G > G508A > T202C > C314T positions. Our results reinforce the current knowledge that secretors are more susceptible to infection by both rotavirus and norovirus than non-secretors. The high rate for Lewis negative (17.1%) and the combination of SNPs, beyond the secretor status, may reflect the highly mixed population in Brazil.

scholarly journals Second Generation Antipsychotics (SGAs) in Schizophrenic Patients and Bipolar Disorder: Correlation With Metabolic Syndrome (NCEP ATP III(a))

2018 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Consuelo Roldan Menco ◽  
Anderson Díaz-Pérez ◽  
Zoraida Barrios Puerta
Keyword(s):  
Metabolic Syndrome ◽  
Bipolar Disorder ◽  
Second Generation ◽  
Mental Illnesses ◽  
Abdominal Circumference ◽  
High Density Lipoproteins ◽  
P Value ◽  
Antipsychotic Treatment ◽  
The Metabolic Syndrome ◽  
Second Generation Antipsychotics

INTRODUCTION: The Metabolic Syndrome is a set of diverse clinical situations such as diabetes mellitus, hypertension and dyslipidemia. Patients with mental illnesses such as schizophrenia or bipolar disorder have a higher mortality than the general population attributable in 60% to somatic diseases and metabolic syndrome, where second generation antipsychotics increase the risk of weight gain and insulin resistance. Objectives. Correlate the treatment with second generation antipsychotics (SGAs) as a possible predictor for Metabolic Syndrome according to the NCEP ATP III (a) classification. METHODS: Descriptive, cross-sectional correlational study. The sample was of 92 patients, applying an open and convenience sampling due to the mental state of the patients in order to determine their degree of acceptance to the study (Informed Assent) and consent to the legal guardian as the main inclusion criterion. For the analysis, the following variables were considered: blood pressure, weight, height, abdominal circumference, serum levels of triglycerides, glucose and high density lipoproteins. The SPSS 20.0 ® program was used logistic regression analysis with a p-value <0.05 and a confidence level of 95%. RESULTS: SGAs most used was clozapine (54.3%). The correlation analysis showed that sociodemographic aspects such as personal history, habits, physical activity and paraclinical and anthropometric records correlated with the possible diagnosis of metabolic syndrome (p <0.05), but not with SGAs (p> 0.05). ). CONCLUSION: No correlation was found between the presence of the metabolic syndrome and the type of antipsychotic treatment.

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