Dissertations / Theses on the topic 'Antipsychotic drugs'
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1
Mahmoud, Ahmed Mohamed. "Antipsychotic drugs and sexual function in schizophrenia." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493418.
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Sexual function is an important aspect of human experience and may significantly contribute to quality of life. For patients with schizophrenia, the impact of the antipsychotic drugs on sexual functions is an area to be researched. Most of the newer antipsychotic drugs have a different mood of action which is believed to account for the low incidence of extra pyramidal side effects and hyperprolactinemia.
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Melkersson, Kristina. "Influence of antipsychotic drugs on hormone levels /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4089-4/.
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Duncan, Carlotta Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "Molecular expression analyses of mice treated with antipsychotic drugs." Publisher:University of New South Wales. Clinical School - St Vincent's Hospital, 2008. http://handle.unsw.edu.au/1959.4/41239.
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Schizophrenia is a devastating psychiatric disorder that affects approximately 1% of the population. The main treatments for schizophrenia are antipsychotic drugs that target dopamine receptors, yet the underlying biological mechanisms through which they alleviate the symptoms of schizophrenia remain ill defined. In this study, we used microarray analysis to profile the expression changes of thousands of genes simultaneously, following antipsychotic drug treatment of mice. Mice were treated chronically (28 days), or for a novel intermediate time-point (7 days), with one of three antipsychotic drugs: clozapine, haloperidol or olanzapine. The use of three drugs enabled us to discern antipsychotic-specific effects co-regulated by multiple drugs, rather than the side effects of individual compounds. Transcript profiling and validation by quantitative PCR of whole brain tissue revealed antipsychotic drug regulation of genes in diverse biological pathways, including: dopamine metabolism, neuropeptide and second-messenger signalling, neurogenesis, synaptic plasticity, cell adhesion, myelination, and voltage-gated ion channels. The regulation of voltage-gated channels by antipsychotic drugs has been suggested previously by electrophysiological studies, although thorough analysis has not been undertaken in vivo. Therefore, the second aim of this study was to characterise the regional mRNA and protein expression of two genes altered by multiple APDs, the voltage-gated potassium channel ??-subunit (Kcna1) and voltage-gated potassium channel interacting protein (Kchip3). Regional characterisation and expression analyses were carried out by immunohistochemistry, in situ hybridisation, and Western blot analysis of mouse brain regions of interest to schizophrenia and its treatment. Following 7-day haloperidol treatment we observed up-regulation of Kcna1 in the striatum and dentate gyrus, with increased protein in the striatum, hippocampus and midbrain; and down-regulation of Kchip3 in the striatum, with decreased protein in the cortex, hippocampus and midbrain. These studies implicate voltage-gated potassium channels in the antipsychotic drug regulation of midbrain dopaminergic neuronal activity, adult neurogenesis and/or striatothalamic GABAergic neuronal inhibition. These findings indicate that regulation of potassium channels may underlie some of the mechanisms of action of antipsychotic drugs, and that voltage-gated ion channels may provide alternative drug targets for the treatment of schizophrenia.
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Grottick, Andrew John. "The temporal effects of typical and atypical antipsychotic drugs." Thesis, London Metropolitan University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297507.
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Tuninger, Eva. "Depot neuroleptic maintenance treatment clinical, pharmacological and neuropsychological aspects /." Lund : Dept. of Psychiatry, Lund University, University Hospital MAS, 1997. http://catalog.hathitrust.org/api/volumes/oclc/40281424.html.
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Rudissaar, Ruth. "Neuropharmacology of atypical antipsychotics and an animal model of psychosis /." Online version, 2006. http://dspace.utlib.ee/dspace/bitstream/10062/1294/5/rudissaarruth.pdf.
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王漪雯 and Belinda Wong. "Haloperidol metabolism in man and animals." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1993. http://hub.hku.hk/bib/B3121194X.
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Mobini, Sirous. "Behavioural analysis of the roles of the ascending monoaminergic pathways and the orbitofrontal cortex in impulse control and motivation." Thesis, University of Nottingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368261.
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D'Souza, Ursula M. "Structure of the Dâ†2 dopamine receptor." Thesis, University of Kent, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259680.
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Furmidge, Lesley Jane. "Effects of partial dopamine D2 agonists on d-amphetamine-induced behaviour." Thesis, University of Reading, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280506.
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Wong, Belinda. "Haloperidol metabolism in man and animals /." [Hong Kong] : University of Hong Kong, 1993. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13671546.
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Taylor, Anita Margaret. "The discriminative stimulus properties of the atypical antipsychotic clozapine." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367204.
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López, Muñoz Laura. "Homology modeling and structural analysis of the antipsychotic drugs receptorome." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7228.
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Classically it was assumed that the compounds with therapeutic effect exert their action interacting with a single receptor. Nowadays it is widely recognized that the pharmacological effect of most drugs is more complex and involves a set of receptors, some associated to their positive effects and some others to the side effects and toxicity. Antipsychotic drugs are an example of effective compounds characterized by a complex pharmacological profile binding to several receptors (mainly G protein-coupled-receptors, GPCR). In this work we will present a detailed study of known antipsychotic drugs and the receptors potentially involved in their binding profile, in order to understand the molecular mechanisms of the antipsychotic pharmacologic effects.The study started with obtaining homology models for all the receptors putatively involved in the antipsychotic drugs receptorome, suitable for building consistent drug-receptor complexes. These complexes were structurally analyzed and compared using multivariate statistical methods, which in turn allowed the identification of the relationship between the pharmacological properties of the antipsychotic drugs and the structural differences in the receptor targets. The results can be exploited for the design of safer and more effective antipsychotic drugs with an optimum binding profile.
Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principalmente a receptores unidos a proteína G, GPCR). El trabajo de la presente tesis se ha centrado en el estudio de los mecanismos moleculares que determinan el perfil de afinidad de unión por múltiples receptores de los fármacos antipsicóticos.
En primer lugar se construyeron modelos de homología para todos los receptores potencialmente implicados en la actividad farmacológica de dichos fármacos, usando una metodología adecuada para construir complejos fármaco-receptor consistentes. La estructura de estos complejos fue analizada y se llevó a cabo una comparación mediante métodos estadísticos multivariantes, que permitió la identificación de asociaciones entre la actividad farmacológica de los fármacos antipsicóticos y diferencias estructurales de los receptores diana. Los resultados obtenidos tienen interés para ser explotados en el diseño de fármacos antipsicóticos con un perfil farmacológico óptimo, más seguros y eficaces.
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Konradsson, Åsa. "Modulation of prefrontal glutamatergic transmission and "atypicality" of antipsychotic drugs /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-344-3/.
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Hertel, Peter. "On the mechanisms of action of atypical antipsychotic drugs : an experimental study /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3634-X/.
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Varty, Geoffrey Brian. "Investigations into prepulse inhibition : a proposed in vivo model for schizophrenia." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309718.
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Bennett, Joanna. "Community psychiatric nurse practice in assessing side effects of antipsychotic drugs." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309696.
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Fathalla, Salem Mehdi. "Cardiotoxic effects of antipsychotic drugs in therapeutic doses and in overdose." Thesis, University of Newcastle upon Tyne, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.547996.
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Shoemaker, Danton L. "Examination of Sexual Differences in the Acute Effects of Haloperidol on Licking." Thesis, University of North Texas, 2015. https://digital.library.unt.edu/ark:/67531/metadc822780/.
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Schizophrenia is a debilitating psychiatric condition affecting almost one percent of the US population. Typical antipsychotics (e.g., haloperidol) have been in use for several decades and are generally very effective in treating the emotional and cognitive effects of schizophrenia, but are used as the last line of treatment due to their severe extrapyramidal motor side effects under chronic exposure. The present study was conducted to investigate the role of sex in determining the oromotor side effects of typical antipsychotics via measuring different behavioral dimensions of male and female Sprague-Dawley rats licking sucrose after haloperidol treatment. The results showed a stronger sensitivity in female rats than male rats within total licking responses and inter-lick intervals. The present results suggest closer attention needs to be paid to the role that sexual hormones play in the motor slowing and behavior-reducing effects of antipsychotics.
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Purcell, Gregory Mark. "Intervention to improve the level of documentation of antipsychotic related adverse drug reactions." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/10340.
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Antipsychotic drugs are the mainstay of treatment for psychotic disorders according to the Standard Treatment Guidelines (2012). However, these drugs are associated with multiple severe adverse drug reactions. In order to limit the effect of adverse drug reactions on patient care, documentation is necessary. Documentation of adverse drug reactions entails recording the reaction experienced, as well as supplementary information. Proper documentation can prevent future occurrences of the same or similar adverse drug reactions. The aim of this study was to determine the effects of an educational intervention targeting increasing documentation of the adverse effects of antipsychotic drugs. The objectives of the study were: to determine the pre-intervention extent and frequency of documentation of antipsychotic-related adverse drug reactions in the patient medical record; to implement an intervention aimed at educating the relevant healthcare professionals, focusing on the adverse drug reactions of antipsychotic drugs and how to record or document these reactions; to assess the post-intervention extent and frequency of documentation of antipsychotic-related adverse drug reactions in the patient medical record; and to assess the attitude of healthcare providers towards the documentation of antipsychotic related adverse drug reactions before and after the intervention.
21
Öhman, Daniel. "Bioanalytical development for application in therapeutic drug monitoring : focus on drugs used in psychiatry /." Linköping : Univ, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med775s.pdf.
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Mustard, Colette J. "The impact of antipsychotic drugs on the expression of genes associated with obesity." Thesis, University of the Highlands and Islands, 2016. https://pure.uhi.ac.uk/portal/en/studentthesis/the-impact-of-antipsychotic-drugs-on-the-expression-of-genes-associated-with-obesity(3e4585b2-4892-4bed-a673-41ab0d83f673).html.
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Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medications. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic variants associated with obesity risk; however the effects of these risk variants on clozapine-induced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling event by which clozapine could induce a change in mRNA expression of the obesity-related genes? The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression of most obesity-related genes tested was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway. In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesity-related genes.
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East, Simon Zachary. "5-htâ†6 and 5-HTâ†7 receptor gene expression in schizophrenia." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343531.
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Lam, Yee-wa, and 林義華. "Prevalence of and factors associated with antipsychotic drug use in private old aged homes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46053141.
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Zhang, Zhi Jun. "Investigation into membrane lipid peroxidation and antioxidant defence enzymes in schizophrenia." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310764.
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Avalos, Melva Nidia. "Partial agonist interactions with dopamine in clonal cell lines expressing recombinant receptors : towards a molecular model of antipsychotic drug action /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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Gruber, Susanne H. M. "Novel mechanism of action of antipsychotic drugs : effects on neuropeptides in rat brain /." Stockholm : [Karolinska institutets bibliotek], 2002. http://diss.kib.ki.se/2002/91-7349-229-9.
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Håkansson, Kerstin. "Regulation of signal transduction in the striatum by typical and atypical antipsychotic drugs /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-360-4/.
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Bantick, Ralph Alexander. "The 5-HTâ‚A receptor in schizophrenia and its occupancy by antipsychotic drugs." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409342.
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Chandratre, Chaitanya. "Medicare drug plan formulary response to the patent expiration of atypical antipsychotics in the State of Washington for fiscal year 2010." Pullman, Wash. : Washington State University, 2010. http://www.dissertations.wsu.edu/Thesis/Spring2010/C_Chandratre_042310.pdf.
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Thesis (M.H.P.A.)--Washington State University, May 2010.Title from PDF title page (viewed on July 20, 2010). "Department of Health Policy and Administration." Includes bibliographical references (p. 30-35).
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Lau, Chuk-ping, and 劉祝屏. "The effect of antipsychotics on blood glucose level/lipid level of patients with mental illness." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206545.
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Objective
The study is to explore the relationship between antipsychotics and blood glucose level or lipid level of patients with mental illness in psychiatric outpatient clinic of Queen Mary Hospital.
Participants and Methods
Case reviews through Clinical Management System were carried out. Total 108 psychotic cases involved in the study. 24 were excluded as the patients did not have any treatment of antipsychotics. 84 patients were qualified for review. 40 females and 68 males involved. Their ages are between 13 and 68.
Patients’ demographics information, blood glucose level or lipid level were retrieved. Some important findings are also noted. Data collection carried in May 2014.
Results
There are no significant changes in fasting blood glucose or lipid level for either typical or atypical antipsychotics. We found that the frequency of checking blood glucose or lipid level was too low and not regular.
Risperidone and Olanzapine are the most commonly used in this psychiatric outpatient clinic. Moreover, 9 cases change from psychosis to Paranoid type schizophrenia. The most frequent diagnosis in the clinic is Paranoid type schizophrenia. 36 cases, one third of the samples, are diagnosed as Paranoid type schizophrenia.
Conclusions
Although we cannot conclude the effect of antipsychotics on blood glucose level or lipid level of patients with mental illness, there is an increasing concern about antipsychotics leading to metabolic problems through the case reviews. We suggest that routine physical health screening, guidelines setting up, predictors should be carried out in the clinic.published_or_final_version
Psychological Medicine
Master
Master of Psychological Medicine
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Tien, Yu-Yu. "Factors associated with the prescription of antipsychotics : Medicare utilization and costs in 2004." Pullman, Wash. : Washington State University, 2009. http://www.dissertations.wsu.edu/Thesis/Spring2009/Y_Tien_042109.pdf.
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Thesis (M.H.P.A.)--Washington State University, May 2009.Title from PDF title page (viewed on Apr. 13, 2010). "Department of Health Policy and Administration." Includes bibliographical references (p. 37-46).
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Duncan, Julianne Christine. "Correlates and Predictors of Medication Noncompliance in Patients with Schizophrenia." Thesis, University of North Texas, 1995. https://digital.library.unt.edu/ark:/67531/metadc277730/.
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The treatment of schizophrenia today consists of a multi-component system of services. Mental health professionals generally agree that anti-psychotic medications are an essential treatment for schizophrenia. However, adherence to medication regimens by patients with schizophrenia is notoriously poor. To identify correlates and predictors of medication compliance, the Schedule for Affective Disorders and Schizophrenia (SADS), a semi-structured diagnostic interview, was administered to 90 outpatients with schizophrenia. The results suggest that there are specific variables (i.e., mood symptoms, psychotic symptoms, and socio-demographic variables) that predict medication compliance. In addition, the confirmation of these variables was effective (90.0%) at identifying non-compliant patients. The results suggest that schizophrenia is a complex disorder composed of heterogeneous symptoms. However, a specific group of symptoms is proposed which may provide a screening measure for predicting patients who are likely to be non-compliant with their medications.
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Barrett, S. L. "Aspects of cognitive function in healthy volunteers administered antipsychotic drugs and in patients with bipolar disorder." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395452.
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Davis, Benjamin. "Glutamatergic regulation of dopamine in the rat frontal cortex : intermediary mechanisms and the effects of antipsychotic drugs." Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242204.
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Lynch, G. M. "The psychopharmacology of antipsychotic drugs : studies of their effects on measures of attention in patients and healthy volunteers." Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268999.
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Marcus, Monica M. "Mechanism of action of antipsychotic drugs: focus on the nucleus accumbens and the prefrontal cortex : an experimental study /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-284-5/.
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Smith, Samantha Jane. "Amino acid neurotransmitter function in the prefrontal cortex : neurochemical basis for modulation via potential targets for antipsychotic drugs." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401170.
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Schmidt, Karl F. "Development of Pharmacological Magnetic Resonance Imaging Methods and their Application to the Investigation of Antipsychotic Drugs: a Dissertation." eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/114.
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Pharmacological magnetic resonance imaging (phMRI) is the use of functional MRI techniques to elucidate the effects that psychotropic drugs have on neural activity within the brain; it is an emerging field of research that holds great potential for the investigation of drugs that act on the central nervous system by revealing the changes in neural activity that mediate observable changes in behavior, cognition, and perception. However, the realization of this potential is hampered by several unanswered questions: Are the MRI measurements reliable surrogates of changing neural activity in the presence of pharmacological agents? Is it relevant to investigate psychiatric phenomena such as reward or anxiolysis in anesthetized, rather than conscious animals? What are the methods that yield reproducible and meaningful results from phMRI experiments, and are they consistent in the investigations of different drugs?
The research presented herein addresses many of these questions with the specific aims of
1) Developing pharmacological MRI methodologies that can be used in the conscious animal,
2) Validating these methodologies with the investigation of a non-stimulant, psychoactive compound, and
3) Applying these methodologies to the investigation of typical and atypical antipsychotic drugs, classes of compounds with unknown mechanisms of therapeutic action
Building on recent developments in the field of functional MRI research, we developed new techniques that enable the investigator to measure localized changes in metabolism commensurate with changing neural activity. We tested the hypothesis that metabolic changes are a more reliable surrogate of changes in neural activity in response to a cocaine challenge, than changes observed in the blood-oxygen-level-dependent (BOLD) signal alone. We developed a system capable of multi-modal imaging in the conscious rat, and we tested the hypothesis that the conscious brain exhibits a markedly different response to systemic morphine challenge than the anesthetized brain. We identified and elucidated several fundamental limitations of the imaging and analysis protocols used in phMRI investigations, and developed new tools that enable the investigator to avoid common pitfalls. Finally, we applied these phMRI techniques to the investigation of neuroleptic compounds by asking the question: does treatment with typical or atypical antipsychotic drugs modulate the systems in the brain which are direct or indirect (i.e. downstream) substrates for a dopaminergic agonist?
The execution of this research has generated several new tools for the neuroscience and drug discovery communities that can be used in neuropsychiatric investigations into the action of psychotropic drugs, while the results of this research provide evidence that supports several answers to the questions that currently limit the utility of phMRI investigations. Specifically, we observed that metabolic change can be measured to resolve discrepancies between anomalous BOLD signal changes and underlying changes in neural activity in the case of systemically administered cocaine. We found clear differences in the response to systemically administered morphine between conscious and anesthetized rats, and observed that only conscious animals exhibit a phMRI response that can be explained by the pharmacodynamics of morphine and corroborated by behavioral observations. We identified fundamental and drug-dependent limitations in the protocols used to perform phMRI investigations, and designed tools and alternate methods to facilitate protocol development.
By applying these techniques to the investigation of neuroleptic compounds, we have gained a new perspective of the alterations in dopaminergic signaling induced by treatment with antipsychotic medications, and have found effects in many nuclei outside of the pathways that act as direct substrates for dopamine. A clearer picture of how neuroleptics alter the intercommunication of brain nuclei would be an invaluable resource for the classification of investigational antipsychotic drugs, and would provide the basis for future studies that examine the neuroplastic changes that confer therapeutic efficacy following chronic treatment with antipsychotic medications.
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Chou, Yuan-Hwa. "A PET study on dopamine and serotonin receptor binding in the primate brain : challenges with antipsychotic drugs and amphetamine /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4639-6/.
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Delgado, Sallent Cristina 1994. "Neural substrates of psychotic-like states and cognitive impairment in a mouse model of schizophrenia and subsequent rescue by antipsychotic drugs." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2021. http://hdl.handle.net/10803/672990.
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Disruption of communication in brain circuits involving the prefrontal cortex (PFC) and the hippocampus (HPC) has been suggested to be a hallmark characteristic of schizophrenia. Therefore, a better understanding of the prefrontal-hippocampal neural basis of schizophrenia’s symptoms is essential for the development of new treatments. In the present thesis, we investigated the alterations of prefrontal-hippocampal circuits in the phencyclidine, acute and subchronic (sPCP), mouse model of schizophrenia and how some of these alterations can be recovered by antipsychotic drugs. We recorded neural activity in the PFC and HPC of C57BL/6J mice. Acute administration of PCP produces hypersynchronization and disrupted communication of PFC-HPC pathways that are recovered by atypical antipsychotic drugs. Furthermore, the sPCP-treated mice showed brain state alterations in gamma oscillations and theta-gamma cross-frequency coupling. Notably, auditory perception, working memory and long-term memory were profoundly impaired in sPCP-treated mice and were accompanied by disrupted prefrontal-hippocampal functional connectivity. Finally, the subchronic risperidone treatment was able to recover memory deficits, but was unable to restore the basal circuit dynamics.Una de las características distintivas la esquizofrenia, es la perturbación de la comunicación de los circuitos cerebrales que incluyen la corteza prefrontal (CPF) y el hipocampo (HPC). Por lo tanto, un mejor entendimiento de las bases neurales de los circuitos prefronto-hipocampales durante los síntomas de la esquizofrenia es esencial para el desarrollo de nuevos tratamientos. En esta tesis, hemos investigado las alteraciones en los circuitos prefrontal-hipocampales en un modelo de esquizofrenia en ratones basado en el tratamiento de fenciclidina, agudo o subcrónico (sPCP), y cómo estas alteraciones pueden ser recuperadas por antipsicóticos Para poder llevar esto a cabo, hemos registrado actividad neural simultáneamente en la CPF y HPC de ratones C57BL/6J. La administración aguda de PCP produce híper sincronización y perturba la comunicación de los circuitos prefronto-hippocampales. Estas alteraciones pueden ser recuperadas por antipsicóticos atípicos. Además, los ratones tratados con sPCP muestran alteraciones de circuito en las oscilaciones gamma y en el acoplamiento cross-frecuencia theta-gamma. Particularmente, el tratamiento sPCP perjudica la percepción auditiva, la memoria de trabajo y la memoria a largo plazo. Todas estas alteraciones van acompañadas de alteraciones en la conectividad funcional de los circuitos prefronto-hipocampales. Finalmente, el tratamiento subcrónico de risperidona es capaz de recuperar los déficits de memoria, pero es incapaz de restaurar las dinámicas prefronto-hipocampales basales.
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Valiente, Gómez Alicia. "Caracterización clínica y biológica de la esquizofrenia con predominio de síntomas negativos." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/401870.
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La esquizofrenia es un trastorno que ha sido ampliamente estudiado y en el que la aparición de los primeros fármacos antipsicóticos, a partir de la década de los 50, resultó una gran revolución en el control de muchos de los síntomas que comporta, como son los delirios y las alucinaciones, conocidos también como síntomas positivos. Pero el papel de los fármacos antipsicóticos sobre los llamados síntomas negativos de la esquizofrenia (apatía, abulia, escasa implicación en actividades sociales y disminución de la expresividad emocional) ha sido mucho más limitado, teniendo escaso impacto sobre ellos. Esto ha hecho que grandes esfuerzos se hayan dirigido a la búsqueda de nuevas dianas de tratamiento y nuevas estrategias terapéuticas orientadas a la mejoría de los síntomas negativos. La correcta tipificación de los síntomas negativos resulta un aspecto clave a la hora de buscar nuevas estrategias de tratamiento. En las últimas décadas se han desarrollado diversas escalas clínicas para su cuantificación y medida, pero su uso ha evidenciado claras limitaciones psicométricas. Ante este panorama, recientemente se han elaborado nuevas escalas clínicas que, sin estas limitaciones, nos permiten cuantificar de manera más eficaz estos síntomas. Entre ellas, la versión inglesa de la escala CAINS (Entrevista Clínica de Evaluación de Síntomas Negativos) ha demostrado unas características óptimas en la cuantificación de los síntomas negativos. Por otro lado, la búsqueda de marcadores biológicos periféricos con el objetivo de predecir el pronóstico, evolución, respuesta al tratamiento y clasificar mejor los trastornos psiquiátricos también ha sido un foco para la investigación en psiquiatría. Marcadores inflamatorios, inmunológicos o neurotróficos han sido objeto de estudio con este propósito. Se ha evidenciado que algunos factores neurotróficos, como el factor neurotrófico derivado del cerebro (BDNF), podrían tener un papel clave en la etiología y/o fisiopatología de las enfermedades mentales, y en concreto en la esquizofrenia. En este contexto, se considera que establecer una tipificación más exhaustiva de los síntomas negativos de la esquizofrenia es un tema de elevado interés en el campo de la esquizofrenia. Por ello, los esfuerzos de esta tesis doctoral se han centrado en la tipificación de los síntomas negativos de la esquizofrenia; por un lado en la tipificación clínica, a través de la traducción al español y validación de la versión española de la escala CAINS para la medida de los síntomas negativos de la esquizofrenia, presentada en el experimento 1, y la tipificación biológica, a través de la búsqueda de un biomarcador sanguíneo periférico (BDNF) que se asocie a los síntomas negativos en pacientes con esquizofrenia, presentada en el experimento 2 de esta tesis doctoral.Schizophrenia is a disorder that has been extensively studied but the role of antipsychotic drugs on the so-called negative symptoms of schizophrenia (apathy, abulia, poor involvement in social activities, and decreased emotional expressiveness) has been much more limited, with little impact on them. Great efforts have been directed to the search for new targets of treatment and new therapeutic strategies oriented to the improvement of negative symptoms. In the last decades, several clinical scales have been developed for quantification and measurement, but their use has evidenced clear psychometric limitations. Given this scenario, new clinical scales have recently been developed that, without these limitations, allow us to quantify these symptoms more effectively. Among them, the English version of the CAINS (Clinical Interview for the Evaluation of Negative Symptoms) scale has demonstrated optimal characteristics in the quantification of negative symptoms. On the other hand, the search for peripheral biological markers with the aim of predicting prognosis, evolution, response to treatment and better classifying psychiatric disorders has also been a focus for research in psychiatry. It has been shown that some neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), may play a key role in the etiology and / or pathophysiology of mental illness, particularly schizophrenia. In this context, it is considered that establishing a more comprehensive classification of the negative symptoms of schizophrenia is a subject of high interest in the field of schizophrenia. For this reason, the efforts of this doctoral thesis have focused on the typification of the negative symptoms of schizophrenia. So the objectives of this thesis are: the clinical typification, through the translation into Spanish and validation of the Spanish version of the CAINS scale for the measurement of negative symptoms of schizophrenia, and biological typing, through the search for a biomarker (BDNF) that is associated with negative symptoms in patients with schizophrenia.
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Joubert, Andre Francois. "Implementation of international treatment guidelines in the treatment of schizophrenia : a study of the effects of an evidence-based seminar on the knowledge and treatment habits of a sample of international psychiatrists." Thesis, Stellenbosch : University of Stellenbosch, 2007. http://hdl.handle.net/10019.1/1322.
Full textAbstract:
Thesis (DMed (Psychiatry))--University of Stellenbosch, 2007.This study reports on the effect of seminar education by studying changes in knowledge, attitude and behaviour to haloperidol prescribing patterns of psychiatrists who In summary, this study demonstrated a direct relationship between seminar attendance and changes to selected minimum effective haloperidol dose and duration of treatment. However, seminar attendance did not appear to be a significant factor in changes to antipsychotic class used for treatment and changes in optimal effective haloperidol dose: rather a change in the level of “background” knowledge of participants was most likely responsible. This study also found individual participant characteristic differences in those who did change treatment duration and minimum effective dose. In conclusion, this study showed that the successful integration of international treatment recommendations into daily psychiatric practise could be facilitated by the use of appropriate educational seminars. Not all attendees benefit i.e. “learn”, but those needing to “learn” most do - i.e. those who need to change their prescribing habits most to meet internationally accepted guidelines. The peer exposure provided allows a format for informed discussion and the practise of evidence-based medicine. The judicious use of such seminars should result in better treatment options and outcomes for patients.attended evidence-based schizophrenia seminars presented by the Lundbeck Institute in Denmark. The objectives of the study were two-fold. Firstly, it set out to determine whether changes actually occurred in the post-seminar haloperidol prescribing behaviour of participants. This was done by analysing changes in choice of optimal haloperidol dose (both in acute treatment i.e. most effective dose and maintenance treatment i.e. minimum effective dose), selected duration of treatment (for first- and multi-episode schizophrenia patients) and drug-class used (conventional versus new generation antipsychotic). The study then investigated whether these changes (if they occurred) could be ascribed wholly or in part to the effect of schizophrenia seminar attendance, or whether other factors e.g. scientific progress over time in understanding schizophrenia and its treatment (“background” knowledge) and differences between participant datasets studied (only paired pre- and post-seminar data were used in this study) also played a role. Secondly, it attempted to identify factors predictive of seminar participants changing their haloperidol prescribing behaviour post-seminar i.e. what were the factors that predisposed some attendees to change their prescribing behaviour? This was done by analysing the effect that pre-seminar prescribing behaviour, participant nationality, patient caseload, work experience and workplace environment had on post-seminar behaviour. Results show that changes did occur in post-seminar haloperidol prescribing behaviour, but that they were not always due to an effect of seminar attendance. Only the changes in the minimum effective haloperidol dose and duration of treatment for first- and multi-episode schizophrenia patients could validly be ascribed to the effects of schizophrenia seminar attendance. Furthermore, multivariate analysis of the factors relating to these changes found that a participant was most likely to change their selected minimum effective haloperidol dose to be more in line with internationally accepted standards if they i) selected above the target dose pre-seminar, ii) had a relatively low caseload comprised mainly of schizophrenia patients and iii) came from either Greece, Germany, Britain, Spain, Italy or some other Eastern European country. The single most important factor related to changes in duration of treatment was found to be pre-seminar behaviour: respondents below the recommended duration of treatment increased their duration of treatment significantly.
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Dezi, Cristina. "Modeling of 5-HT2A and 5-HT2C receptors and of theirs complexes with actual and potential antypsichotic drugs." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7127.
Full textAbstract:
La presente tesis "Modelling of 5-HT2A and 5-HT2C receptors and of their complexes with actual and potential antipsychotic drugs" tiene como objetivo de profundizar los conocimientos actuales sobre el mecanismo de acción de los fármacos antipsicóticos. En este proyecto de larga duración, se han construidos modelos computacionales de los receptores 5-HT2A y 5-HT2C, utilizando un nuevo protocolo de modelización basado sobre los datos experimentales de otras proteínas GPCR de la misma familia. Las estructuras 3D se han validado e utilizado en estudios de acoplamiento ligando-receptor, simulaciones de dinámica molecular, y estudios 3D-QSAR con el ligando natural (serotonina), un agonista inverso bien conocido (ketanserina) y una serie de butyrofenonas con afinidad para ambos subtipos receptoriales. Las metodologías directas e indirectas utilizadas, han permitido de comprender mejor los elementos claves que gobiernan el acoplamiento ligando - receptor, mediante la identificación de los residuos más involucrados en esta interacción, el rol de la quiralidad de los ligandos y también las posiciones alternativas de acoplamiento que algunos ligandos pueden asumir en el sitio de unión de los receptores.Los resultados son coherentes con los datos experimentales y su interpretación ha proporcionado información valiosa, difícilmente obtenible con la simple inspección visual de las estructuras de los ligandos y de los receptores.This thesis "Modelling of 5-HT2A and 5-HT2C receptors and of their complexes with actual and potential antipsychotic drugs" has the objective of investigate the mechanism of action of antipsychotic drugs. During the development of this project, computational models of 5-HT2A and 5-HT2C receptors have been built, by means of a new modeling protocol based on experimental data from other GPCR of the same family. 3D structures have been validated by means of docking, molecular dynamic simulations and 3D-QSAR studies, using the natural ligand (serotonin), a well known inverse agonist (ketanserin) and a series of butyrophenones with affinity for both receptor subtypes. Direct and indirect methodologies have been applied, allowing a better comprehension of the key elements governing the ligand-receptor docking, thanks to the identification of the most important residues that stabilize such interaction, role of chirality and alternative positions within the binding site. The results are coherent with experimental data and its interpretation provided valuable information, not available at a simple visual inspection of ligand - receptor structures.
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Oliveira, Nícolas Gustavo Matias de. "Soroprevalência de toxoplasmose e avaliação de genotoxicidade em indivíduos diagnosticados com esquizofrenia expostos a xenobióticos." Universidade Federal de Goiás, 2018. http://repositorio.bc.ufg.br/tede/handle/tede/8295.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Schizophrenia (EQZ) is a chronic mental illness that affects about 1% of the world population and is characterized by behavioral domains such as positive symptoms characterized by hallucinations and delusions and negative symptoms that involve apathy, anhedonia and social blunting. The cause of EQZ remains unknown, but it is known to be a disease whose etiology involves environmental and genetic factors. Several studies seek to identify factors that clarify the etiology of the disease. The agent that causes toxoplasmosis, Toxoplasma gondii, seems to be related to the development and progression of the disease, evidenced by studies that argue that T. gondii infection may be a triggering factor for psychosis in some individuals, since the parasite has a certain tropism by the central nervous system. Furthermore, studies have reported parasite infection as a factor related to genotoxicity, including toxoplasma infection in an animal model. Based on the foregoing, the present study aimed to evaluate the seropositivity to T. gondii (IgM or IgG) and the avidity of IgG in a group of individuals diagnosed with EQZ in the city of Goiânia and to evaluate the occurrence of genotoxicity in these, of genotoxicity with exposure to xenobiotics such as tobacco, alcohol, especially drugs, and / or T. gondii infection. Seropositivity was observed above 70% among individuals diagnosed with EQZ in relation to the controls, with avidity above 50%, indicating that individuals had contact with T. gondii at some time prior to the survey. Despite the genotoxic damage found, there was no significant difference in genotoxic damage among the infected individuals evaluated. The present study did not demonstrate that T. gondii may be a contributing factor to the occurrence of DNA damage, and the use of antipsychotic drugs, tobacco and alcohol, despite being a risk factor for genotoxicity, did not demonstrate an influence significant difference in the present study. However, it is necessary to carry out other analyzes and investigate parameters such as the time of drug use and exposure to other xenobiotics. In order to know better the life habits of individuals, it may help to provide more information about this relationship between T. gondii and EQZ.
A esquizofrenia (EQZ) é uma doença mental crônica que afeta cerca de 1% da população mundial e se caracteriza por domínios comportamentais, como sintomas positivos, caracterizados por alucinações e delírios e sintomas negativos, que envolvem apatia, anedonia e embotamento social. A causa da EQZ ainda permanece desconhecida, mas sabe-se que se trata de uma doença que cuja etiologia envolve fatores ambientais e genéticos. Vários estudos buscam identificar fatores que esclareçam a etiologia da doença. O agente causador da toxoplasmose, Toxoplasma gondii, parece ter relação com o desenvolvimento e progressão da doença, evidenciado por estudos que defendem que a infecção por T. gondii pode ser um fator desencadeante de psicoses em alguns indivíduos, já que o parasito apresenta um certo tropismo pelo sistema nervoso central. Ainda, estudos tem reportado a infecção por parasitos como fator relacionado a genotoxicidade, incluindo a infecção pelo toxoplasma em um modelo animal. Com base no exposto, o presente trabalho teve por objetivo avaliar a soropositividade para T. gondii (IgM ou IgG) e a avidez da IgG em um grupo de indivíduos diagnosticados com EQZ do município de Goiânia e avaliar a ocorrência de genotoxicidade nestes, procurando relação da genotoxicidade com a exposição a xenobióticos como tabaco, álcool, especialmente medicamentos, e/ou com a infecção pelo T. gondii. Observou- se soropositividade acima de 70% entre os indivíduos diagnosticados com EQZ em relação aos controles, com avidez acima de 50%, indicando que os indivíduos tiveram contato com o T. gondii em algum momento anterior a pesquisa. Apesar do dano genotóxico encontrado, não houve diferença significativa no dano genotóxico entre os indivíduos infectados avaliados. O presente estudo não demonstrou que T. gondii pode ser um fator contribuinte para a ocorrência de danos ao DNA, e o uso de fármacos antipsicóticos, o fumo e o álcool, apesar de serem um fator de risco para a genotoxicidade, não demonstraram uma influência significativa no presente estudo. Entretanto, há a necessidade de realizar outras análises e investigar parâmetros como o tempo de uso dos fármacos, e de exposição a outros xenobióticos, enfim, o melhor conhecimento dos hábitos de vida dos indivíduos pode ajudar a trazer mais informações acerca dessa relação entre T. gondii e a EQZ.
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Oosthuizen, P. P. (Petrus Paulus). "Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa." Thesis, Stellenbosch : Stellenbosch University, 2003. http://hdl.handle.net/10019.1/49804.
Full textAbstract:
Dissertation (PhD)--Stellenbosch University, 2003.ENGLISH ABSTRACT: Although schizophrenia is traditionally viewed as an illness with a very poor prognosis, research over the last few years indicates that early intervention may substantially improve the long-term outcome of this disorder. Several studies suggest that patients with first-episode psychosis (FEP) are more sensitive to, and require lower doses of antipsychotic medications than patients with more chronic forms of illness. However, the optimal dose of first-generation anti psychotics in patients with FEP has not been explored extensively and continues to be a controversial subject. This study evaluated the efficacy and safety of low-dose haloperidol in a South African cohort with FEP. The study was conducted in two phases: Phase 1 was an open-label, naturalistic study of 57 subjects with FEP who were commenced on 1mg of haloperidol for 4 weeks, after which gradual escalation of doses were allowed, if required. Subjects who failed to respond at haloperidol 10mg per day were switched to thioridazine. Failure to respond to thioridazine 600mg per day was interpreted to indicate treatment resistance. These subjects were then commenced on clozapine. The principal finding of this phase of the study was that the majority of subjects could be stabilized and maintained on very low doses of haloperidol (1.7 ± 1.0 mg/day at 12 months and 1.3 ±0.8 mg/day at 24 months). Ratings for extra-pyramidal side-effects did not increase significantly from baseline over the duration of the study, except in the case of tardive dyskinesia (TD), where a substantial number of subjects (12.3%) developed TD within 12 months of starting treatment. Phase 2 of the study was a double-blind, randomized controlled trial of low-dose (2mg/day) versus "standard dose" (8mg Iday) haloperidol. Forty subjects were included in this phase of the study; 20 in each treatment arm. The main finding was that there were no significant differences in treatment reponse between the two treatment groups. There were, however, significant differences between the two treatment groups in extrapyramidal side effects (EPSE), with the 8mg per day group exhibiting significantly higher levels of EPSE than the 2mg per day group. This was manifested by significant differences in scores on the Extrapyramidal Symptom Rating Scale (ESRS) and the Simpson-Angus Rating Scale. Furthermore, subjects in the 8mg haloperidol per day group required significantly higher doses of anticholinergic medication and had significantly higher mean levels of prolactin at the end of the study period. This study indicates that a majority of subjects with first-episode psychosis can be treated and maintained successfully with very low doses of haloperidol. It also shows that low-dose treatment is as effective as, and better tolerated than, "standard" doses. Despite the success with the low-dose treatment, however, there was still a much higher than expected incidence of tardive dyskinesia, a serious and potentially irreversible side-effect of neuroleptic treatment.
AFRIKAANSE OPSOMMING: Hoewel skisofrenie tradisioneel gesien is as 'n siekte met 'n uiters swak prognose, dui navorsing oor die afgelope jare daarop dat vroeë ingryping die langtermynuitkoms van hierdie toestand drasties mag verbeter. Resultate van verskeie studies dui daarop dat pasiënte met eerste-episode psigose (EEP) nie net meer sensitief is vir antipsigotiese middels nie, maar ook laer dosisse daarvan benodig tydens behandeling as pasiënte met meer kroniese vorms van psigotiese siekte. Desondanks is die kwessie van die korrekte dosis van eerste generasie antipsigotika in hierdie groep nog onvolledig nagevors en bly dit 'n omstrede onderwerp. Hierdie studie het ten doel gehad om die effektiwiteit en veiligheid van lae dosis haloperidol in 'n Suid-Afrikaanse populasie van pasiënte met EEP te evalueer. Die studie is uitgevoer in twee fases: Fase 1 was 'n oop, naturalistiese studie van 57 pasiënte met EEP wat aanvanklik behandel is met 1mg haloperidol per dag vir 4 weke, waarna geleidelike verhoging van dosisse toegelaat is, soos nodig. Diegene wat nie bevredigende respons getoon het op haloperidol 10mg per dag nie, is oorgeskakel na tioridasien. Ontoereikende respons teen 600mg/dag tioridasien is geïnterpreteer as 'n aanduiding van behandelingsweerstandigheid en behandeling met klosapien is begin. Die belangrikste bevinding van hierdie fase van die studie was dat die meerderheid pasiënte gestabiliseer en in stand gehou kom word op baie lae dosisse haloperidol (1.7 ± 1.0 mg/dag op 12 maande en 1.3 ±0.8 mg/dag op 24 maande). Metings van ekstra-piramidale newe-effekte (EPNE) het nie beduidend toegeneem oor die duur van die studie nie, behalwe in die geval van tardiewe diskinese (TO), waar 'n beduidende aantal pasiënte (12.3%) TO ontwikkel het binne 12 maande na aanvang van behandeling. Fase 2 van die studie was 'n dubbelblinde, ewekansig gerandomiseerde studie waarin behandeling met lae dosis haloperidol (2mg/dag) vergelyk is met "standaard" dosis haloperidol (8mg/dag). Veertig pasiënte is ingesluit in hierdie fase van die studie, 20 in elke behandelingsarm. Die hoofbevinding was dat daar geen beduidende verskille in respons op behandeling was tussen die twee groepe nie. Daar was egter beduidende verskille in EPNE, waar die 8mg/dag groep beduidend hoër vlakke van EPNE gehad het as die 2mg/dag groep. Hierdie verskil in EPNE is aangedui deur 'n statisties beduidende verskil in tellings op die Extrapyramidal Symptom Rating Scale (ESRS) en die Simpson- Angus Rating Scale. Verder het pasiënte in die 8mg/dag groep beduidend hoër dosisse antikolinerge medikasie benodig en ook hoër gemiddelde prolaktienvlakke gehad teen die einde van studie. Hierdie studie dui dus daarop dat die meerderheid van pasiënte met EEP suksesvol behandel en in stand gehou kan word met baie lae dosisse haloperidol. Die studie wys ook daarop dat behandeling met lae dosisse net so effektief is en beter verdra word as behandeling met "standaard" dosisse. Ten spyte van die suksesvolle gebruik van lae dosisse medikasie het die studie egter ook getoon dat daar "n baie hoër as verwagte insidensie was van TO, "n emstige en potensieelonomkeerbare newe-effek van neuroleptiese behandeling.
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Widerlöv, Birgitta. "Long-Term Functional Psychosis : Epidemiology in Two Different Counties in Sweden." Doctoral thesis, Uppsala University, Department of Neuroscience, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7466.
Full textAbstract:
This thesis is based on two independent studies, the first in Stockholm County (index year 1984; n=302), and the second, a replication and validation study, in Uppsala County (index year 1991; n=455).
The general aim was to study all individuals with Long-term Functional Psychosis (LFP) within the two counties of Sweden from an epidemiological perspective and to perform specific studies on a subgroup of individuals with schizophrenia. In the Stockholm study, the total one-year LFP prevalence was 5.3/1 000; in the the rural, suburban and urban areas it was 3.4, 5.6 and 6.6/1 000, respectively. The total one-year prevalence of LFP in Uppsala was 7.3/1 000; in the rural, peripheral city and central city areas it was 6.0, 7.0, and 8.7/1 000, respectively.
Within the non-schizophrenic subpopulation, a pronounced difference was demonstrated between the two studies with substantially higher prevalence rates in the Uppsala study. The schizophrenic subgroup in Uppsala was re-diagnosed using parallel diagnostic systems (DSM-III, DSM-III-R, DSM-IV and ICD-10), and reasonably comparable prevalence estimates were obtained.
In both studies antipsychotic drugs were most frequently prescribed for the patients with schizophrenia, and the doses were considered as low to moderate. In the Uppsala study the doses of antipsychotic drugs decreased with a longer duration of illness, while the opposite was found in the Stockholm study.
The increased mortality rate among patients with schizophrenia was mainly due to unnatural causes of death and cardiovascular diseases, particularly among males.
The main methodological differences between the two studies were in the sampling procedures. In the Uppsala study, a larger number of care facilities were screened, and a broader set of diagnostic criteria were used for identifying cases from different registers.
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Goikolea, Alberdi José Manuel. "Propiedades reguladoras del humor de los antipsicóticos atípicos en los episodios afectivos del trastorno bipolar." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/107704.
Full textAbstract:
La aparición de los antipsicóticos atípicos o de segunda generación ha supuesto un gran cambio en el manejo de los pacientes con trastorno bipolar. Los ensayos controlados han demostrado la eficacia de prácticamente todos los antipsicóticos atípicos en la manía aguda. Además, la mayor parte de ellos disponen de datos positivos para el tratamiento de mantenimiento del trastorno bipolar, lo que sugiere propiedades normotímicas. E incluso algunos de ellos han mostrado datos positivos en la depresión bipolar. Sin embargo, apenas existen estudios independientes comparando la acción de los atípicos con la de los clásicos, mas allá del uso de haloperidol como comparador activo en algunos estudios de manía aguda.
En este contexto, esta tesis tiene como objetivo evaluar el comportamiento de los antipsicóticos atípicos en las fases de manía aguda y depresión, en comparación con el de los antipsicóticos clásicos (haloperidol) y placebo respectivamente, para testar las posibles propiedades normoreguladoras en los episodios agudos.
Se utilizaron para ello las técnicas de metanálisis, estructurándose la tesis en dos metanálisis separados. El primero en manía aguda, comparando antipsicóticos atípicos con antipsicóticos clásicos. Dentro de este metanálisis se escogieron dos variables principales: la velocidad de inicio de acción, operativizada como la disminución en la puntuación en la escala de manía a la primera semana, y el viraje depresivo. En los dos casos, se trata de variables de interés clínico, escasamente estudiadas hasta la actualidad, y que señalan el perfil de acción de los fármacos. En segundo lugar, se llevó a cabo un segundo metanálisis comparando la acción de los antipsicóticos atípicos con la del placebo (no existían estudios comparativos con antipsicóticos clásicos) en depresión bipolar.
Los resultados de la primera variable del metanálisis en manía aguda, que dan lugar al primer artículo de esta tesis, confirman que el haloperidol muestra un inicio de acción más rápido que los antipsicóticos atípicos. El tamaño del efecto fue pequeño (SMD = 0,17 [0,01 - 0,32] tal como cabria esperar entre dos grupos de eficacia demostrada. Sin embargo, este resultado sugiere que el haloperidol puede seguir siendo un tratamiento de primera línea en la manía aguda en casos graves en los que se requiere una mejoría sintomática urgente, siempre y cuando el riesgo de efectos adversos extrapiramidales y de viraje depresivo sea bajo.
El segundo artículo de la tesis analiza las diferencias en el riesgo de viraje depresivo tras el tratamiento de la manía aguda con antipsicóticos atípicos en comparación con haloperidol. El resultado del metanálisis es que los atípicos conllevan un 42% menos de riesgo de viraje que el haloperidol. No obstante, se observa heterogeneidad en este análisis y las diferencias entre grupos son atribuibles especialmente a la acción de tres de los atípicos: olanzapina, quetiapina, y ziprasidona.
El segundo metanalisis, que da lugar al tercer lugar de la tesis, observa que existe un efecto positivo en la depresión bipolar, en comparacion con placebo, pero que solo es atribuible a algunos de los antipsicóticos atípicos, concretamente, a la olanzapina y la quetiapina. De modo que se concluye que no se trata de un efecto de clase de la familia.
Analizando los resultados de los dos metanálisis en conjunto se observa que se puede establecerse un gradiente en función de la afinidad por el receptor dopaminergico D2, modulado por la acción sobre otros receptores, en el que la mayor afinidad y selectividad antiD2 supondría mayor potencia antimaníaca, inicio de acción antimaníaca más rápido, mayor riesgo de viraje depresivo, e ineficacia y/o agravamiento de la depresión bipolar. Haloperidol se situaría en el extremo izquierdo del gradiente y se propone la siguiente ubicación para los antipsicóticos atípicos: Risperidona – Aripiprazol – Ziprasidona – Olanzapina – Quetiapina. Además, este gradiente coincide con el de los valores del Índice de Polaridad obtenidos en los estudios de prevención de recurrencias con los antipsicóticos atípicos, de lo que se desprende que los efectos en los episodios agudos tiende a perdurar durante el tratamiento de mantenimiento.Introduction of atypical antipsychotics has involved a great change in the management of bipolar disorder during last decade. Not only they show efficacy in mania, but also for recurrence prevention, and some of them have also been shown to work in bipolar depression. However, comparisons with classical neuroleptics to assess advantages and disadvantages are scarce. In this context, the goal of this thesis was to assess the behavior of atypical antipsichotics in the acute phases of mania and depression, compared to classical antipsychotics in the former and with placebo in the latter, and study their possible normothymic properties. Metanalysis techniques were used. The thesis was structured in two different metanalysis. The first one in acute mania, comparing atypical and classical antipyschotics. Two different outcomes were assessed: speed of onset of action and switch to depression. The second metanalysis studied the efficacy of atypical antipsychotics in bipolar depression versus placebo. The first article of the thesis shows that haloperidol has a faster onset of action than atypical antipsychotics in acute mania. The size of the effect was small (SMD = 0,17 [0,01 - 0,32] but could still be clinically significant in the subset of severe manic patients who require an urgent relief of symtpoms. On the other hand, as it is shown in the second paper of the thesis, treatment with atypicals involves a 42% reduction in the risk of switch to depression compared to haloperidol. However, heterogeneity was present which could be due to differences in the group of atypicals, as three of them (olanzapine, quetiapine, and ziprasidone) could explain the effect. The third article, corresponding to the second metanálisis, shows only some atypicals, namely olanzapine and quetiapine, are efficacious in bipolar depression. Therefore, there is no class effect. A global view of both metanalysis shows that dopaminergic D2 affinity is likely to be the most important factor over the different profile of antipsychotics, with lower affinity involving more clear normothymic actions.
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Katajceva, Liubov. "Antipsichotinių preparatų suvartojimo tendencijos Lietuvoje 2003-2005 metais. Antipsichotinių preparatų efektyvumo įvertinimas. Meta-analizė." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2006. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2006~D_20060720_145250-87105.
Full textAbstract:
Objective: To evaluate trends in the use of antipsychotic drugs in Lithuania between 2003 and 2005 years.
Methods: The data on total sales of antipsychotic drugs in all Lithuanian regions over three years (2003-2005) were obtained from IMS Health Inc. Drugs were classified according to the Anatomic Therapeutic Chemical system and use was quantified in terms of defined daily doses. Meta-analysis of observational studies retrieved through systematic search of all available electronic data sources. 1651 abstracts were found and checked. 76 randomised double-blind studies were identified for the met-analysis. Data were calculated by DDD methodology and expressed in DDDs per 1.000 inhabitants per day. The pharmacoeconomic analysis of antipsychotics was performed by cost minimization and reference price methodology.
Results: In Lithuania the total antipsychotics consumption increased by 16% over three years (2003-2005) period reaching the value of 5,5 DDD/1000 inhabitants/day. Since 2003 the proportion of use of conventional antipsychotics has increased by 2%, while the use of atypical antipsychotics has increased by 14%. The expenditures of antipsychotics has reached 39 mln Litas (in 2005), of which 48% was costs for atypical antipsychotic agents. Setting the reference price of risperidone (according to the meta-analysis results of effectiveness) for atypical antipsychotics it would be possible to rationalize schizophrenia treatment using 10,68 mln Litas extra money.
Conclusions:... [to full text]
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González, Rodríguez Alexandre. "Biomarcadors de resposta farmacològica en dones postmenopàusiques amb esquizofrènia." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664133.
Full textAbstract:
INTRODUCCIÓ:
La menopausa és un procés caracteritzat per un decliu en els nivells d’estrògens, i és per tant un període de vulnerabilitat biològica en dones amb esquizofrènia. Amb la present tesi es pretèn investigar variables clíniques, reproductives i hormonals capaces de influenciar la resposta antipsicòtica en l’esquizofrènia a la menopausa. Aquesta tesi està formada per dos articles: el primer (Estudi 1) investiga si la resposta antipsicòtica difereix d’acord a la influència de l’exposició acumulada d’estrògens i el temps succeït des de la menopausa, quines dimensions psicopatològiques responen millor i quines variables influencien més aquestes dimensions. El segon article (Estudi 2) pretèn correlacionar no només els nivells d’hormones gonadals, sino els nivells de FSH, LH i la ràtio FSH/LH amb la millora en símptomes clínics específics en dones postmenopàusiques amb esquizofrènia.
MÈTODES:
L’estudi 1 avalua 64 dones postmenopàusiques amb esquizofrènia que realitzen seguiment a 12 setmanes en un estudi prospectiu. L’exposició acumulada als estrògens al llarg de la vida i el temps transcorregut des de la menopausa van ser analitzats com a potencials predictors de la resposta antipsicòtica. Es van realitzar anàlisis de regressió per investigar l’associació entre potencials factors confusors i la resposta antipsicòtica. A l’estudi 2, van participar 37 dones postmenopàusiques amb esquizofrènia en fase aguda, tractades amb un nou antipsicòtic determinat per necessitats clíniques, en un estudi prospectiu observacional a 12 setmanes. Es van obtenir nivells sèrics d’hormones gonadals, FSH i LH, a nivell basal. Es van realitzar anàlisis de correlació parcial entre les variables clíniques i hormonals, realitzant una correcció de Bonferroni per a ajustar els resultats.
RESULTATS:
L’estudi 1 va mostrar que 42 participants (66%) van ser responedores a antipsicòtics. El temps transcorregut des de la menopausa es va associar estadísticament i negativament amb la resposta antipsicòtica global, explicant gairebé el 42% de la variància del model. Per tant, l’estudi 1 suggereix que la resposta antipsicòtica empitjora amb la durada de la menopausa. A l’ajustar els resultats per les múltiples comparacions realitzades, els assajos hormonals que vam realitzar a l’estudi 2 no van provar una associació significativa amb la millora clínica en cap dels dominis simptomàtics de l’esquizofrènia.
CONCLUSIONS:
Un període de temps perllongat des de la menopausa es va associar negativament amb la resposta antipsicòtica en esquizofrènia després de la menopausa. Els nivells d’hormones gonadals, FSH, LH i la ràtio FSH/LH, un índex de pobra resposta ovàrica, no es van associar amb la millora clínica a la menopausa en dones amb esquizofrènia. L’eix hipotalàmic-pituïtari-adrenal prèn un paper en aquestes edats. Per aquest motiu, la relació entre les hormones gonadals i adrenals i la resposta antipsicòtica requereix de més investigacions.INTRODUCTION: Menopause is a process characterized by a decline in estrogen levels and is therefore a period of biological vulnerability in schizophrenia women. With the present thesis we aimed to investigate clinical, reproductive and hormonal variables capable of influencing antipsychotic response in schizophrenia at the time of menopause. It comprises two articles: the first (Study 1) investigates whether antipsychotic response differs according to the influence of cumulative estrogen exposure and time since menopause, which psychopathological dimensions respond best and what variables best influence them. The second one (Study 2) aims to correlate not only gonadal hormone levels but also FSH, LH and FSH/LH ratio with clinical improvement in postmenopausal schizophrenia women. METHODS: Study 1 assessed 64 postmenopausal schizophrenia women in a 12-week prospective design. Lifetime cumulative estrogen exposure and time since menopause were tested as predictors of antipsychotic response. Regression analyses were performed to investigate the association between confounding factors and antipsychotic response. In study 2, 37 acutely ill postmenopausal schizophrenia women with a newly initiated, clinically determined change in antipsychotic medication, participated in a 12-week prospective observational study. Circulating gonadal hormone serum levels, FSH and LH levels were obtained. Partial correlational analyses were performed between clinical and hormonal variables, along with a Bonferroni significance correction. RESULTS: Study 1 showed 42 participants (66%) as being antipsychotic responders. Time since menopause was negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Thus, study 1 suggested that antipsychotic response worsens with postmenopausal duration. After correction for multiple testing, the hormone assays we did in study 2 did not prove to be significantly linked to clinical improvement in any of the symptom domains. CONCLUSIONS: The time elapsed since menopause was negatively associated with response to antipsychotics in schizophrenia after menopause. Gonadal hormone levels, FSH, LH, and the FSH/LH ratio, an index of poor ovarian response, were not found to be associated with clinical improvement in postmenopausal schizophrenia. The hypothalamic-pituitary-adrenal system may play a role at this age. For this reason, the link between gonadal and adrenal hormones and antipsychotic response bears further investigation.