Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD

2021 ◽  
pp. 026988112110152
Author(s):  
Melike Kevser Gul ◽  
Elif Funda Sener ◽  
Muge Gulcihan Onal ◽  
Esra Demirci

Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter ( NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD. Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at −80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR). Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity. Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

2008 ◽  
Vol 66 (3a) ◽  
pp. 477-481 ◽  
Author(s):  
Karen P. Grisotto ◽  
Isac Bruck ◽  
Sérgio A. Antoniuk ◽  
Lúcia H.C. Santos

OBJECTIVE: To evaluate the efficacy or eventual side-effects of the association of lamotrigine and sodium valproate in the control of refractory epilepsies. METHOD: A retrospective analysis of 37 children with a mean age of 12 years taking exclusivelly lamotrigine and sodium valproate. Efficacy of seizure control was considered satisfactory if there was a reduction in seizures >50% or total control. RESULTS: The association of lamotrigine and sodium valproate was considered satisfactory in 65% of the studied children, independent of seizure type. Total seizure control was obtained in 33% and 35% had an unsatisfactory response or remained unchanged. Primary generalized tonic clonic seizures were the most common type with 84% of day-time seizures having a good response to treatment. Side-effects were seen in 11% of patients and the most common was tremor. CONCLUSION: Total or satisfactory control of seizures was seen in the majority of patients and side-effects were uncommon.


Author(s):  
C.H. Waters

Abstract:The use of the combination of fluoxetine, an anti-depressant serotonin uptake inhibitor, and selegiline, a monoamine oxidase -B inhibitor, was reviewed in a large population of patients with Parkinson’s disease. All records were reviewed from a Parkinson’s disease clinic to determine how many patients were treated simultaneously with selegiline and fluoxetine. Patient characteristics, duration and dose of treatment, side effects and reasons for discontinuation were noted. Twenty-three patients received both medications at the same time. No additional side effects were noted with the combination therapy that had not already been reported with each medication alone. No serious side effects were found. In this clinic population, fluoxetine and selegiline were used in combination without major side effects, but further observation is warranted.


2016 ◽  
pp. 25-29
Author(s):  
Van Huy Tran ◽  
Thi Huyen Thuong Nguyen

Background: Data about efficacy of Tenofovir in patients of HBV –related cirrhosis in Vietnam was still limited. This study is aimed at: - evaluating the clinical, biochemical, virological and Child-Pugh score responses 3,6,9 months after Tenofovir therapy; - assessing possible side effects of tenofovir. Patients and methods: 40 patients with HBV-related cirrhosis were enrolled. All has received Tenofovir disoproxil fumarate 300mg/day. Follow-up after 3,6 and 9 months. Results: Anorexia, oedema and ascites were significantly improved after treatment. HBV DNA became undetectable in 92.5%, 94.55 and 100% after 3,6 and 9 months, respectively. Child- Pugh score was improved after treatment (5.94±0.22 after treatment vs 7.47±0.28 before treatment). Side effects were minors (nausea, vomiting). No case of increase in serum creatinine was found. Conclusion: Tenofovir showed effective and safe in patients of HBV-related cirrhosis. Key words: Cirrhosis, tenofovir, HBV. Key words: cirrhosis, tenofovir, HBV


2021 ◽  
Vol 13 ◽  
pp. 1759720X2110140
Author(s):  
Conor Magee ◽  
Hannah Jethwa ◽  
Oliver M. FitzGerald ◽  
Deepak R. Jadon

Aims: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). Methods: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included. Results: A total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review’s eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA. Conclusion: Several studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice.


CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 173-173
Author(s):  
Amir Levine ◽  
Kelly Clemenza ◽  
Shira Weiss ◽  
Adam Bisaga ◽  
Erez Eitan ◽  
...  

AbstractBackgroundOpioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rana Harhay ◽  
Wajiha Jeelani ◽  
Barbine Tchamba Agbor Agbor ◽  
Teresa Hennon ◽  
Brian H. Wrotniak ◽  
...  

Abstract Background Oligo-articular juvenile idiopathic arthritis (Oligo JIA) is the most common subtype of juvenile idiopathic arthritis. Intra-articular corticosteroid (IAC) injection is a mainstay treatment of oligo JIA providing pain relief, improving mobility and preventing further joint destruction in the majority of patients. In 2015, production of triamcinolone hexacetonide (TH) an intra-articular corticosteroid was discontinued in the United States leading to use of triamcinolone acetonide (TA) as an alternative. In this study, we compared response to treatment in children with oligo JIA who underwent therapy with intra-articular TA and TH injection. Methods Our study is a retrospective chart review of children with oligo JIA who were treated with IAC injections with TH between January 2012 and June 2015 and TA between J uly 2015 and December 2018. The two groups were followed at John R. Oishei Children’s Hospital of Buffalo and were evaluated for response to treatment, side effects and predictors of response including duration of disease before treatment, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Response to treatment was defined as at least 6 months follow up without evidence of active arthritis in injected joints. Patients were considered to be non-responders if they continued to show active arthritis during their first follow up after joint injection. The primary objective was to evaluate whether there was a significant difference in rate of response between TH and TA. Results Forty-nine patients, 38 female and 11 male with oligo JIA were included in the study. The average age was 6.7 years. A total of 111 joints were injected includin g 78 knees, 13 ankles, 9 wrists, 4 hips, 4 elbows, 2 TMJ and one subtalar joint. In the TA group, 49% (29/59) did not show response to injection compared to 27% (14/52) in the TH group. After 6 months, response rates were better for individuals injected with TH compared to TA (73% vs. 51%). In general, response to intra-articular TH was superior to TA with P = .016 using chi-square test of independence. This difference in outcome was not influenced by other variables such as duration of illness before treatment (P value 0.784) or elevated ESR and CRP. No difference in side effects between the two groups were noted. Conclusion Our results in conjunction with prior published data suggests that TH intra-articular joint injection in oligo JIA is superior to TA, although future controlled trials are necessary for confirmation. An effective, long lasting treatment can have a great impact on the outcome of these children.


Author(s):  
Weam Fageera ◽  
Boris Chaumette ◽  
Marie-Ève Fortier ◽  
Natalie Grizenko ◽  
Aurelie Labbe ◽  
...  

2013 ◽  
Vol 6 (1) ◽  
pp. 342 ◽  
Author(s):  
Katie Butcher ◽  
Beverley-Ann Biggs ◽  
Karin Leder ◽  
Chris Lemoh ◽  
Daniel O’Brien ◽  
...  

2021 ◽  
Vol 11 (5) ◽  
pp. 335
Author(s):  
María José Zarzuelo Romero ◽  
Cristina Pérez Ramírez ◽  
María Isabel Carrasco Campos ◽  
Almudena Sánchez Martín ◽  
Miguel Ángel Calleja Hernández ◽  
...  

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.


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