Browsing by Subject "pharmacotherapy"

Now showing 1 - 5 of 5
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    The association of COMT genotype with buproprion treatment response in the treatment of major depressive disorder
    (Wiley, 2020-05-27) Fawver, Jay; Flanagan, Mindy; Smith, Thomas; Drouin, Michelle; Mirro, Michael; BioHealth Informatics, School of Informatics and Computing
    Background Pharmacodynamics and pharmacogenetics are being explored in pharmacological treatment response for major depressive disorder (MDD). Interactions between genotype and treatment response may be dose dependent. In this study, we examined whether MDD patients with Met/Met, Met/Val, and Val/Val COMT genotypes differed in their response to bupropion in terms of depression scores. Methods This study utilized a convenience sample of 241 adult outpatients (≥18 years) who met DSM‐5 criteria for MDD and had visits at a Midwest psychopharmacology clinic between February 2016 and January 2017. Exclusion criteria included various comorbid medical, neurological, and psychiatric conditions and current use of benzodiazepines or narcotics. Participants completed genetic testing and the 9 question patient‐rated Patient Health Questionnaire (PHQ‐9) at each clinic visit (M = 3.8 visits, SD = 1.5) and were prescribed bupropion or another antidepressant drug. All participants were adherent to pharmacotherapy treatment recommendations for >2 months following genetic testing. Results Participants were mostly Caucasian (85.9%) outpatients (154 female and 87 male) who were 44.5 years old, on average (SD = 17.9). For Val carriers, high bupropion doses resulted in significantly lower PHQ‐9 scores than no bupropion (t(868) = 5.04, p < .001) or low dose bupropion (t(868) = 3.29, p = .001). Val carriers differed significantly from Met/Met patients in response to high dose bupropion (t(868) = −2.03, p = .04), but not to low dose bupropion. Conclusion High‐dose bupropion is beneficial for MDD patients with Met/Val or Val/Val COMT genotypes, but not for patients with Met/Met genotype. Prospective studies are necessary to replicate this pharmacodynamic relationship between bupropion and COMT genotypes and explore economic and clinical outcomes.
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    MOLECULAR AND CELLULAR MECHANISMS LEADING TO SIMILAR PHENOTYPES IN DOWN AND FETAL ALCOHOL SYNDROMES
    (Office of the Vice Chancellor for Research, 2011-04-08) Solzak, Jeffrey P.; Zhou, Feng; Roper, Randall J.
    Down syndrome (DS) and Fetal Alcohol Syndrome (FAS) are two leading causes of birth defects with phenotypes ranging from cognitive impairment to craniofacial abnormalities. These syndromes have an estimated occurrence of 1/750 and 1/1000 live births, respectively. While DS originates from the trisomy of human chromosome 21 and FAS from excess alcohol consumption, many of the defining characteristics for these two disorders are stunningly similar. Our research of the published literature has identified more than 20 similarities in DS and FAS phenotypes including precise craniofacial and neurological abnormalities. We hypothesize that the similar phenotypes in these two syndromes are caused by disruptions in common molecular and cellular pathways. To test our hypothesis we are examining morphometric, genetic, and cellular phenotypes during development of DS and FAS mouse models. Our preliminary evidence indicates that during early development, expression of Dyrk1a and Rcan1 (two genes found in three copies in individuals with DS) is dysregulated in the craniofacial and neurological precursors of both DS and FAS as compared to normal control embryos. Using immuocytochemistry, we are analyzing cellular properties of neurological development in DS embryos and comparing deficiencies found between trisomic and normal mice to those found in FAS embryos at similar stages. These results will further define molecular and cellular alterations leading to DS and FAS phenotypes and provide mechanisms to target for potential pharmacotherapy.
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    Pharmacotherapy of Hypertension in Chronic Dialysis Patients
    (American Society of Nephrology, 2016-11-07) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of Medicine
    Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.
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    PREGMED: Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health
    (Office of the Vice Chancellor for Research, 2010-04-09) Haas, D.M.; Denne, S.C.; Flockhart, D.F.; Haneline, L.S.; Renbarger, J.L.
    Many illnesses occur in pregnant women and children that can significantly impact health. These conditions require drug therapy but the clinical pharmacology and pharmacogenomics of most medications used during pregnancy and childhood are poorly characterized. This compromises the effective and individualized treatment of multiple conditions specific to these populations such as nausea and vomiting of pregnancy, preterm labor, diabetes, and depression in pregnant women and childhood cancers in pediatric patients. Furthermore, drug disposition in these populations is known to be different from that observed in non-pregnant adults. We have developed PREGMED a unique center whose central mission is to improve the pharmacotherapy for women and children using a personalized medicine approach that builds on the strengths of Indiana University in the areas of pharmacogenomics and clinical obstetrics and pediatrics. The center’s multidisciplinary activities focus on developing new paradigms for the treatment of the multiple important conditions that affect pregnant women and children.
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    Rat Animal Models for Screening Medications to Treat Alcohol Use Disorders
    (Elsevier, 2017) Bell, Richard L.; Hauser, Sheketha R.; Liang, Tiebing; Sari, Youssef; Maldonado-Devincci, Antoinette; Rodd, Zachary A.; Department of Psychiatry, IU School of Medicine
    The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs. Next, common behavioral tests for drug efficacy will be discussed particularly as they relate to stages in the addiction cycle. Tables highlighting studies that have tested the effects of compounds using the respective techniques are included. Wherever possible the Tables are organized chronologically in ascending order to describe changes in the focus of research on AUDs over time. In general, high ethanol-consuming selectively bred rats have been used to test a wide range of compounds. Older studies usually followed neurobiological findings in the selected lines that supported an association with a propensity for high ethanol intake. Most of these tests evaluated the compound's effects on the maintenance of ethanol drinking. Very few compounds have been tested during ethanol-seeking and/or relapse and fewer still have assessed their effects during the acquisition of AUDs. Overall, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed; the roles of sex- and age-of-animal, as well as the acquisition of AUDs, ethanol-seeking and relapse continue to be factors and behaviors needing further study.