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1
Hughes, Zoe Alexandra. "Modulation of extracellular noradrenaline in rate cortex by selective serotonin reuptake inhibitors (SSRIs)." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300168.
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Carlsson, Björn. "From achiral to chiral analysis of citalopram." Doctoral thesis, Linköpings universitet, Klinisk farmakologi, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-5217.
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Within the field of depression the “monoamine hypothesis” has been the leading theory to explain the biological basis of depression. This theory proposes that the biological basis of depression is due to a deficiency in one or more of three key neurotransmitter systems, namely noradrenaline, dopamine and serotonin which are thought to mediate the therapeutic actions of virtually every known antidepressant agent. Citalopram is a selective serotonin-reuptake inhibitor (SSRI) used for the treatment of depression and anxiety disorders. Citalopram is a racemic compound, in other words composed of a 50:50 mixture of two enantiomers (S-(+)-citalopram and R-(-)-citalopram) and with one of the enantiomers (S-(+)-citalopram) accounting for the inhibitory effect. At the time of introduction of citalopram the physician needed a therapeutic drug monitoring service to identify patients with interactions, compliance problems and for handling questions concerning polymorphic enzymes and drug metabolism. An achiral analytical separation method based on solid-phase extraction followed by high-performance liquid chromatography (HPLC) was developed for routine therapeutic drug monitoring (TDM) of citalopram and its two main demethylated metabolites. As the data available on citalopram were from achiral concentration determinations and to be able to further investigate citalopram enantiomers effects and distribution, a chiral method for separation of the enantiomers of citalopram and its demethylated metabolites was established. The advances within chiral separation techniques have made measurement of the concentrations of the individual enantiomers in biological fluids possible. The process behind enantioselective separation is however not fully understood and the mechanism behind the separation can be further scrutinized by the use of multivariate methods. A study of the optimization and characterization of the separation of the enantiomers of citalopram, desmethylcitalopram and didesmethylcitalopram on an acetylated ß-cyclodextrin column, by use of two different chemometric programs - response surface modelling and sequential optimization was performed. Sequential optimization can be a quicker mean of optimizing a chromatographic separation; response surface modelling, in addition to enabling optimization of the chromatographic process, also serves as a tool for learning more about the separation mechanism. Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent, despite the increasing use of citalopram in these age groups. A study was initiated to investigate adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites. The ratios between the S- and R-enantiomers of citalopram and didesmethylcitalopram were in agreement with studies involving older patients. The concentrations of the S-(+)- and R-(-) enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the polymorphic CYP2C19 enzyme. Even though the SSRIs are considered less toxic compared with older monoamine-active drugs like the tricyclic/tetracyclic antidepressants, the risk of developing serious side effects such as ECG abnormalities and convulsions has been seen for citalopram, when larger doses have been ingested. Furthermore, fatal overdoses have been reported where citalopram alone was the cause of death. Data on the toxicity of each of the enantiomers in humans have not been reported and no data on blood levels of the enantiomers in cases of intoxication have been presented. An investigation was initiated on forensic autopsy cases where citalopram had been found at the routine screening and these cases were further analysed with enantioselective analysis to determine the blood concentrations of the enantiomers of citalopram and metabolites. Furthermore the genotyping regarding the polymorphic enzymes CYP2D6 and CYP2C19 were performed. In 53 autopsy cases, we found increasing S/R ratios with increasing concentrations of citalopram. We found also that high citalopram S/R ratio were associated with high parent drug to metabolite ratio and may be an indicator of recent intake. Only 3.8 % were found to be poor metabolizers regarding CYP2D6 and for CYP2C19 no poor metabolizer was found. Enantioselective analysis of citalopram and its metabolites can provide valuable information about the time that has elapsed between intake and death. Genotyping can be of help in specific cases but the possibility of pharmacokinetic interactions is apparently a far greater problem than genetic enzyme deficiency.On the day of the public defence the status of article IV was: Submitted.
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Baldwin, David S., Ian M. Anderson, David J. Nutt, Christer Allgulander, Borwin Bandelow, Boer Johan A. den, David M. Christmas, et al. "Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology." Sage, 2014. https://tud.qucosa.de/id/qucosa%3A35384.
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This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
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Kirchner, Vincent. "The elderly, arginine vasopressin & selective serotonin reuptake inhibitors." Master's thesis, University of Cape Town, 1999. http://hdl.handle.net/11427/26271.
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The association between selective serotonin reuptake inhibitors (SSRis) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRis from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRis. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. This is probably a sporadic, idiosyncratic phenomenon that is not dose related as A VP function determined by serum and urine concentrations was found to be normal in six elderly patients using sertraline. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of this group to hyponatraemia whilst using SSRis. AIMS & HYPOTHESIS: This dissertation will explore the physiology of Arginine V asopressin and how changes in this system along with other physiological changes in the elderly make the elderly susceptible to hyponatraemia. This problem will then be explored in the context of elderly people with depression using SSRis which are known to cause hyponatraemia. In the first part of the research section the aims are to report the published cases of hyponatraemia occurring whilst using SSRis from the United Kingdom and specifically focus on cases in people 60 years and older. Secondly to re-analyse all case reports in the literature looking only at this population. The third aim was to investigate whether dysregulation of vasopressin function in the elderly using SSRis is a sporadic or usual phenomenon. The null hypothesis is that A VP function is not disturbed by SSRis.
5
Calcagno, Eleonora. "Resistance to selective serotonin reuptake inhibitors : role of serotonergic mechanisms." Thesis, Open University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504263.
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Gordon, Sevelanne. "Selective serotonin reuptake inhibitors and tricyclic antidepressants : novel immunomodulating agents." Thesis, University of Brighton, 2012. https://research.brighton.ac.uk/en/studentTheses/2cb45086-57b5-49ba-ba8e-09fe9c92f710.
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Acute respiratory distress syndrome (ARDS) is an inflammatory disease in humans where no satisfactory therapeutic options exist. Regulation of the immune system by neurotransmitters has been identified as a possible exploitable strategy to treat inflammatory conditions. Antidepressant drugs have been found to have secondary actions including anti-inflammatory activity in a wide range of disease states in vivo. The cellular effects of these drugs that contribute to this effect have yet to be elucidated. The aim was to examine whether anti-depressants have a direct effect on the immune system or an effect on the target tissue such as lung cells. This thesis utilised both primary lung epithelium cells along with the cell lines A549, 16HBE14o- and BETIY02. The macrophage cell line RAW 264.7 was used to determine effects of anti-depressants on immune cells. Mitochondrial function was used as a measure of cell viability while morphological techniques were used to determine levels of apoptosis and necrosis. Cellular cytokine release was used as a determination of inflammation. Nitric oxide production by activated immune cells was measured using the nitrite assay and the expression of inducible nitric oxide synthase measured by Western blot. The BETIY02 cell line was found to have the most similar characteristics to primary lung epithelium cells and could be used as an effective substitute for large-scale screening and mechanistic studies especially in inflammation. Fluoxetine and desipramine reduced the inflammatory signals coming from lung cells exposed to lipopolysaccharide (LPS). In addition to this they proved effective in reducing immune cell activation as evidenced by reduced NO release following LPS exposure via a mechanism of inhibiting iN OS protein expression. Fluoxetine and desipramine exhibited anti-inflammatory effects on both the lung cells and the immune cells, identifying possible therapeutic potential for ARDS.
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Julyan, Tom Everett. "Characteristics and consequences of antenatal exposure to selective serotonin reuptake inhibitors." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30712/.
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Depression is a common condition, affecting around one in 20 people worldwide. It is challenging conceptually and clinically, with treatment being ineffective for many, and significant consequences for individuals and societies alike. Depression is particularly problematic during pregnancy, where it is no less common, but poses additional difficulties. Both depression and its pharmacological treatments are associated with a range of short- and longer- term sequelae for offspring, and current data is insufficient to allow fully informed decisions to be made by mothers, midwives, or doctors. Research is affected by practical, ethical, and methodological issues, and a myriad of confounding factors, which combine to increase uncertainties over the risks and benefits of prescribing (or not). Retrospective and prospective observational studies accompany epidemiological data linkage and meta- analyses involving millions of subjects, in contributing to both current knowledge and testable hypotheses to inform future directions for research, while clinical and preclinical studies with smaller sample sizes provide invaluable and complementary details. However, significant gaps remain, not least in delivering optimal care to each individual mother and baby. While the overall emerging picture appears reassuring to some, others acknowledge that we do not even possess all the pieces of the puzzle yet. There remains an urgent need for more comprehensive and relevant data. This thesis presents the findings from a series of pilot studies on evaluating the characteristics and consequences of antenatal exposure to selective serotonin reuptake inhibitors. Up to one in 10 women in the general Scottish population may be exposed to an antidepressant at some point during pregnancy, but adverse outcomes may be related more to underlying maternal depression, rather than its pharmacological treatment. We highlight areas of both intelligence and ignorance, and make proposals for future research.
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Ashbury, Janet E. "Selective serotonin reuptake inhibitors (SSRIs) and breast cancer : a record linkage study." Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/971.
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Gu, Xiaobo. "Synthesis and SAR study of Meperidine Analogues as Selective Serotonin Reuptake Inhibitors (SSRIs)." ScholarWorks@UNO, 2010. http://scholarworks.uno.edu/td/1111.
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Meperidine has been shown to have potent binding affinity for serotonin transporters (SERT) (Ki = 41 nM) and be an inhibitor of serotonin reuptake. Based upon these pharmacological results meperidine has been identified as a lead compound for the development of a novel class of serotonin-selective reuptake inhibitors (SSRIs). A variety of potent analogues of meperidine have been synthesized and evaluated in vitro as potential ligands for the serotonin transporter. Substitutions have been made on the aryl ring, the ester moiety and the piperidine nitrogen of meperidine. Potent analogues of the aryl substituted series that included 4-iodophenyl, 2-naphthyl, 3,4-dichlorophenyl and 4-biphenyl meperidine derivatives were synthesized and chosen for further optimization of the benzyl ester analogues. Benzyl ester analogues included 4-nitro, 4-methoxyl and 3,4-dichloro benzyl analogues and exhibited high potency for serotonin transporters and high selectivity over the dopamine transporter (DAT) and the norepinephrine transporter (NET). Also the N-demethylated analogues improve the binding affinity and selectivity for serotonin transporter. The analogue 4- (carboxymethoxybenzyl)-4-(4-iodophenyl) piperidine (69f), was found the most potent (Ki=0.6 nM) and selective ligand for serotonin transporter (DAT/SERT >4500; NET/SERT >4500) for the series and has been advanced to in vivo evaluation.
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Mathebe, Ntlatseng Gretta Rhoda. "Fabrication and kinetic modeling of cytochrome P4502D6 amperometric biosensors for serotonin reuptake inhibitors." Thesis, University of the Western Cape, 2005. http://hdl.handle.net/11394/1589.
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Magister Scientiae - MScAn amperometric biosensor was prepared by in situ deposition of cytochrome P4502D6 (CYP2D6, P4502D6) enzyme on a polyaniline (PANI)-doped glassy carbon electrode. The PANI film was electrochemically deposited on the electrode at 100 mV s-1 against Ag/AgCl. Cyclic voltammetric characterisation of the PANI film in 1 M HCl solution showed two distinct redox peaks, which prove that the PANI film was electroactive and exhibited fast reversible electrochemistry. The surface concentration and film thickness of the adsorbed electroactive species was estimated to be 1.85 x 10 -7 mol cm -2 and approximately 16 nm, respectively. Cytochrome P4502D6 was electrostatically immobilised onto the surface of the PANI film and cyclic voltammetry was used to monitor the serotonin reuptake inhibitors (fluoxetine, fluvoxamine and citalopram) in phosphate buffer solution. Fluoxetine was found to be a substrate of CYP2D6 at low concentrations but inhibits enzyme activity at high concentrations; this was consistent with uncompetitive substrate inhibition kinetics. Thus PANI-mediated electrochemistry can be used to observe monooxygenation reaction of CYP2D6.
South Africa
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Briley, Kelly Anne. "The Effects of Selective Serotonin Reuptake Inhibitors (SSRI) on Auditory Measures in Women." Thesis, University of North Texas, 2002. https://digital.library.unt.edu/ark:/67531/metadc3155/.
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This study examined the relationship between selective serotonin reuptake inhibitor (SSRI) medication and auditory measures in clinically depressed women. Experimental subjects were tested in both a medicated and unmedicated condition. Experimental subjects were compared to a normal control group; additionally intrasubject comparison was made within the experimental group. Test measures included: audiometry, tympanometry, otoacoustic emissions, uncomfortable loudness level, masking level difference, SCAN-A, Synthetic Sentence Identification (SSI), and the low predictability section of the Revised Speech in noise (RSPIN). The unmedicated group scored significantly less favorably than the control group on the following tests; SCAN-A (composite, filtered words, and auditory figure ground), R-SPIN (0MCR condition in both the right and left ears). Additionally, the unmedicated group scored significantly less favorably than the medicated group on the SSI (-20MCR condition right ear only) and of the R-SPIN (0MCR condition right ear only). Other test measures indicated consistent trends but did reach significance.
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Carney, Lara E. "A preliminary study on the effect of selective serotonin reuptake inhibitors on peripheral and lower brainstem auditory processing." Thesis, University of North Texas, 2001. https://digital.library.unt.edu/ark:/67531/metadc2765/.
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This study compared auditory behavioral and physiologic measures in normal control subjects and subjects prescribed with a selective serotonin reuptake inhibitor (SSRI) who were yet to take the drug and those currently taking an SSRI. Test measures used were pure tone averages (PTA), acoustic reflex thresholds, uncomfortable loudness levels (UCL), otoacoustic emissions, masking level difference, temporal integration, amplitude resolution, and Beck Depression Inventory-II (BDI-II) scores. Results indicated that there was a significant difference in the amplitude resolution of the unmedicated group when compared to the medicated and the control group. There was also a significant positive correlation between dynamic range (difference between UCL and PTA) and amplitude resolution. The BDI-II revealed a significant difference between the scores of the unmedicated and the control group as well as the medicated and the control group. Although other test measures indicated differences between the groups, the
differences were not statistically significant.
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Kulin, Nathalie A. "Pregnancy outcome following first trimester maternal exposure to the newer selective serotonin reuptake inhibitors." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29322.pdf.
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Kinnear, Helen. "Changes in dream frequency, vividness and intensity in subjects taking selective serotonin reuptake inhibitors." Master's thesis, University of Cape Town, 2005. http://hdl.handle.net/11427/12419.
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Includes bibliographical references (leaves 61-67).Various sources of evidence suggest that dream frequency, intensity and vividness are increased with the use of selective serotonin reuptake inhibitors (SSRJ's) commonly prescribed for depression and anxiety. In this study the effects ofSSRI use on dream frequency, intensity and vividness in psychiatric patients was examined through a comparision of the dream characteristics of an SSRI- medicated patient group vs. an unmedicated patient control group. Each group comprised 20 patients recruited through state psychiatric outpatient facilities affiliated with two research universities. Age and gender were evenly spread across the two groups. Psychiatric disorders represented were generalised an.xiety disorder, panic disorder, obsessive-compulsive disorder and social phobia. Patients completed a questionnaire consisting of a most recent dream report and self-report likert-scaled questions regarding dream frequency, intensity, vividness and memorability. Two independent raters rated the dream reports for intensity on a likert scale. Self-reported visual vividness was significantly higher (p=0.027, effect size .86) among SSRI users compared with controls, whereas selJreported dream frequency and emotional intensity as well as independent raters assessment of dream intensity were not significantly different across the two groups. Findings of increased dream vividness without increases in dream frequency complement the results of an earlier study. Since serotonin is suppressed during REM sleep, these findings cast further doubt upon the notion of an isomorphic link between REM sleep and dreaming and argue for the searchfor a more sophisticated model of neurotransmitter modulation of sleep-cognition.
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Goodale, Elizabeth S. "The Effects of Selective Serotonin Reuptake Inhibitors (Ssri) on Auditory Measures in Clinically Depressed Subjects." Thesis, University of North Texas, 2002. https://digital.library.unt.edu/ark:/67531/metadc3146/.
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The purpose of this study was to investigate the relationship between selective serotonin reuptake inhibitor (SSRI) medication on auditory skills in clinically depressed subjects. Experimental subjects prescribed an SSRI were tested in a medicated and an unmedicated condition, and the test results were compared. Furthermore, the experimental group was compared with a control group consisting of normal subjects. Test measures included pure tone audiometry, tympanometry, acoustic reflex thresholds, and auditory electrophysiologic measures such as auditory brainstem and auditory late responses. An assessment scale for depression (Beck Depression Inventory-II) was also used. Results indicated statistically significant differences for the BDI-II between the control and experimental groups for both conditions. Electrophysiologic measures indicated a significantly shorter latency for auditory late potential P1 at 55 dBnSL, and a significantly larger amplitude at 45 dBnSL for the N1/P2 component for the unmedicated group. Although the other measures showed trends, they did not reach significance.
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Skaring, Ida. "Selective serotonin reuptake inhibitors in the Baltic Sea region : The effects of SSRI on teleost fish." Thesis, Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-35727.
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Pharmaceuticals, enter the aquatic environments through sewage treatment plants and may affect fish. This examination paper is a literature study that focuses on Selective serotonin reuptake inhibitors, SSRIs, exposure and the impacts on teleosts in the Baltic Sea by assessment of peer-reviewed literature and material. Teleosts affected by exposure of these substances may demonstrate physiologically as well as behavioral alterations. These can be observed as alterations in aggression, boldness, mobility, growth, feeding rate or in endocrine processes. The potential of which SSRI may effect teleosts depends on the pH of the aquatic environment, temperature, other contaminants and the fat solubility of the substances. Some effects caused by SSRI exposure may elicit ecological impacts. These particularly concern changes and effects in terms of evasiveness, reproductive capacity and ability to find food as well as alterations of interspecificity. Even the balance between population density, individual fitness and by extension survival might be affected. Effects in interspecificity may potentially lead to local extinctions and changes in food webs. Furthermore, results demonstrated that when a substance is bioaccumulated and the teleosts are eaten by predators on higher trophic levels, marine ecosystems can also be affected. Moreover a conclusion could be drawn the level of concentration of SSRIs in the aquatic environment may be of less significance since teleosts have the potential to bioaccumulate SSRIs in tissue over time and in this sense concentrations may reach harmful levels that can cause physiological or behavioural alterations. Continuous studies should refer to chronic tests studies with focus on a field testing environment for understanding of natural conditions and exposure. Furthermore, studies on how ecosystems may be affected should be important to give an overview of the problem with SSRI exposure. As the Baltic Sea is a sensitive environment, studies should preferable be made on species living in this environment.
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Miranda, Maria Graciela Pinney Kevin G. "Design, synthesis and biological evaluation of novel serotonin reuptake inhibitors and novel derivatives of a nitrogen-containing combretastatin analog." Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/4819.
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Chan, Patrick G. "A pharmacodynamic model of the role of 5-HT2A and GABAA receptors in the delay in the onset of action of SSRIS." Scholarly Commons, 2009. https://scholarlycommons.pacific.edu/uop_etds/2396.
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Depression is a common neuropsychiatric illness with a lifetime prevalence of 17% in the United States. The disease can severely impact the daily living and quality of life in patients. The monoamine hypothesis of depression implicates the neurotransmitter serotonin as mediating the pathophysiology. Selective serotonin reuptake inhibitors (SSRIs), a popular and efficacious class of antidepressants, increase serotonin concentrations in the brain. However, full clinical benefit may not be obtained for four to six weeks. This period of waiting for SSRIs to work becomes quite daunting for patients. Research has focused on delineating the control mechanisms surrounding the dorsal raphé nucleus (DRN), the serotonergic control center located in the midbrain. Much evidence points to changes in several receptor systems as the underlying cause of the delay. One particular serotonin receptor, 5-HT 1A , has been established to play a role in affecting the time course of clinical effect. We have targeted another receptor as a possible contributor to the delay: the stimulatory 5-HT 2A heteroreceptors located on GABAergic interneurons of the DRN. The 5-HT 2A receptors of the GABAergic interneurons receive stimulatory input from serotonergic collaterals branching off the DRN serotonergic neurons. The resultant stimulation causes GABA release and inhibition of the serotonergic neurons via GABA A receptors of the DRN, completing a feedback loop. We hypothesize that the 5-HT 2A receptors desensitize under constant stimulation, as in the case with SSRI administration, and as a result contribute to the time delay in the onset of action of SSRIs. Using the microdialysis technique, various receptor agonists and antagonists were administered to examine receptor changes and its influence on serotonin release in male Wistar rats. Our results demonstrate that GABA A receptors exert a large inhibitory influence on serotonergic neurotransmission. Local GABA release results from 5-HT 2A receptor stimulation. Furthermore, serotonin appears to trend back towards basal levels, suggesting a possible desensitization process occurring under constant agonism of 5-HT 2A receptors. The development of our pharmacodynamic model quantitatively shows a slow desensitization process, which may also contribute to the time delay observed with the onset of action of SSRIs.
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Kim, John. "Pharmacokinetics and pharmacodynamics of the selective serotonin reuptake inhibitors, fluoxetine and paroxetine, during pregnancy and the nursing period." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ61127.pdf.
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Burke-Doe, Annie Patrice. "Body weight -supported gait training in poststroke hemiparetic patients undergoing treatment with serotonin reuptake inhibitors: A pilot study." Scholarly Commons, 2003. https://scholarlycommons.pacific.edu/uop_etds/2637.
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Background and purpose . This pilot study examined SSRI's in association with partial body weight treadmill training (PBWTT) to improve locomotion post stroke. Serotonin is thought to play a role in recovery of motor function such as locomotion on a treadmill eliciting the central pattern generators (CPG's) identified from animal models. There would be benefits in knowing if serotonin combined with PBWTT influenced motor recovery. The purpose of the study was to determine if patients undergoing treatment with an SSRI would improve in locomotor function to a greater degree than patients not receiving an SSRI. Subjects and methods . Non clinically depressed post stroke patients (N = 4) and clinically depressed post stroke patients on SSRI's (N = 4) were assigned to two groups of convenience. Initial baseline performance was established at two evaluation points using functional gait tests, balance tests, and electomyographical analysis during performance of locomotion over an eight week period (Pre 1 & Pre 2). Intervention of PBWTT was introduced for eight weeks and subjects were evaluated again (Post 1). Subjects returned four weeks later for a follow up evaluation (Post 2). The intervention included training three days a week for eight weeks utilizing PBWTT. Data was analyzed using non parametric statistics. Results . All subjects improved in gait velocity, distance covered and assistance needs as it relates to the PBWTT. Functional gait, balance and gait characteristic improved in both groups with significant differences noted in the “timed up and go test” and Tinetti Assessment in the group undergoing treatment with SSRI's. Weight bearing squat scores improved in both groups with a greater significance at 0 and 30 degrees of knee flexion in the subjects under the influence of SSRI's. The limits of stability scores (LOS) and sensory organization test (SOT) improved in both groups without significant differences. Electromyographical data supported visual observations for improvement of gait deviations and improved on-off timing during the gait cycle in both groups. Conclusion . This study would indicate comparing SSRI therapy and specific functional movement learning for further study.
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Stinson, Rebecca Diane. "The impact of persistent sexual side effects of selective serotonin reuptake inhibitors after discontinuing treatment: a qualitative study." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/5061.
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This dissertation details a qualitative study that examined nine individuals living with sexual side effects of SSRIs that had persisted after the discontinuation of pharmacological treatment (referred to as post-SSRI sexual dysfunction or PSSD).
The investigation sought to answer the following research questions:
(1) How do individuals with persistent sexual side effects make sense of and meaning from their experience?;
(2) How have these individuals' sense of self or identity changed over the course of their sexual difficulties?; and
(3) What role could a counseling psychologist have had in helping the individual with his or her situation?
Using Interpretative Phenomenological Analysis methodology, eight themes emerged from the data including:
(1) difficult emotional experiences;
(2) varied coping strategies;
(3) negative impact on romantic relationships;
(4) changed identity;
(5) changed attitude toward sex;
(6) problems with medical providers;
(7) mixed feelings about SSRIs; and
(8) desire for collaborative healthcare.
A review of relevant literature, a detailed explanation of the research methodology, a description of the results incorporating participant narratives, and a discussion of the results highlighting implications for counseling psychologists and limitations of the study are included in this dissertation.
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Bolling, Madelon Y. "Subtle psychological side effects : documentation, description, and treatment implications of subjective experiences of selective serotonin reuptake inhibitors taken for depression /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/9145.
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Beesdo, Katja, James Hartford, James Russell, Melissa Spann, Susan Ball, and Hans-Ulrich Wittchen. "The short- and long-term effect of duloxetine on painful physical symptoms in patients with generalized anxiety disorder: Results from three clinical trials." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-112635.
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Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n = 840) were 9- to 10-week efficacy trials; study 3 (n = 887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0–100; n = 1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p ≤ 0.01). In study 3, pain symptoms worsened in responders switched to placebo compared with those maintained on duloxetine (p ≤ 0.02). In conclusion, duloxetine was efficacious in the short- and long-term treatment of PPS, which are common in GAD patients.
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Júnior, Paulo de Sousa Carvalho. "Pharmaceutical salts of the antidepressants Paroxetine and Fluoxetine, selective serotonin reuptake inhibitors: crystal engineering, solid-state characterization and thermodynamic aspects." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-27012017-084846/.
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The development of new solid forms of active pharmaceutical ingredients (API) is relevant both from fundamental as well as industrial perspectives. To this end, Crystal Engineering plays an ever-increasing important role in pharmaceutical sciences. Among the crystal engineering strategy, salt formation is the most important and implemented approach. The salt forms of API could be used to modulate and tuned the solubility and stability of API to provide optimal practical uses. Herein, we report pharmaceutical salts of two Selective Serotonin Reuptake Inhibitor antidepressants used in the treatment of depression and anxiety disorders, Paroxetine (PRX) and Fluoxetine (FLX). For this purpose, salt formers, supramolecular synthesis and crystallization protocols have been driven by the systematization of structural and supramolecular data of molecules and analogues from the Cambridge Structural Database. Paroxetine bromide hemihydrate ((PRXBr)0.5H2O), Paroxetine Nitrate hydrate (PRXNO3H2O) and two polymorphs of Fluoxetine Nitrate (FLXNO3) have obtained. All were characterized by a combination of techniques including Single Crystal X-ray Diffraction, Differential Scanning Calorimetry (DSC), Thermogravimetry analysis (TGA), Hot Stage Microscopy, Fourier transform infrared spectroscopy (IR) and solubility measurements. Since the hydration/dehydration process in APIs induces phase transitions that compromise its efficiency, the structural characterization of (PRXBr)0.5H2O help to understand its reversible dehydration process. Also, this study has implication in the understating of dehydration of isostructural PRX hydrochloride salt. Additionally, the (PRXNO3)H2O have shown the conformational flexibility and supramolecular diversity of PRX. On the other hand, the chirality of FLX is related to two nitrate salt polymorphs. A racemate and a non-centrosymmetric structure with independent enantiomers in the asymmetric unit were obtained for FLXNO3. Their packing have shown the existence of different racemic motifs, resulting in different enantiomer orientations The rare occurrence of racemic systems in non-centrosymmetric space groups becomes this event a noteworthy case. By their physicochemical properties, the polymorphs were monotropically related. The scientific contributions of this thesis show the diversity of the solid forms and define candidates to new antidepressants APIs solid formulations.O desenvolvimento de novas formas sólidas de ingredientes farmacêuticos ativos (API) é relevante tanto numa perspectiva fundamental como industrial. Para tal, a Engenharia de cristais tem desempenhado um papel importante nas ciências farmacêuticas. Dentre as estratégias, a formação de sais é a abordagem mais importante e implementada. Os sais de APIs são capazes de modular e ajustar a solubilidade e a estabilidade, a fim de proporcionar uso prático. Nesta tese, são reportados sais de dois fármacos Inibidores Seletivos de Recaptação de Serotonina, consolidados no tratamento da depressão e distúrbios de ansiedade, a Paroxetina (PRX) e a Fluoxetina (FLX). Brometo de Paroxetina hemiidratado ((PRXBr)0.5H2O), Nitrato de Paroxetina hidratado (PRXNO3H2O) e polimorfos de Nitrato de Fluoxetina (FLXNO3), síntese e protocolos de cristalização foram cuidadosamente delineados, com base na sistematização de dados estruturais e supramoleculares das moléculas e seus análogos, depositados no Cambridge Structural Database. Todos os sais foram caracterizados por Difração de Raios-X por Monocristal, Calorimetria Explanatória Diferencial (DSC), Análise termogravimétrica (TGA), Termomicroscopia, Espectroscopia vibracional na região do infravermelho (IR) e solubilidade. Considerando que a hidratação/desidratação induz mudanças de fases que comprometem a eficiência do API, a caracterização do (PRXBr)0.5H2O auxiliou no entendimento do processo de desidratação reversível que ocorre para esse fármaco. Estas mudanças de fase resultam também em implicações sobre a compreensão do processo de desidratação do sal isoestrutural de cloreto de PRX hemiidratado. Além disso, por meio da elucidação estrutural do (PRXNO3)H2O, foi possível analisar a diversidade conformacional e supramolecular da PRX. Quanto à FLX, verificou-se que sua quiralidade está relacionada com seu polimorfismo. Um racemato e uma estrutura não centrossimétrica com dois enatiômeros independentes na unidade assimétrica foram obtidos para o FLXNO3. A comparação destas estruturas permitiu mostrar a existência de arranjos supramoleculares racêmicos, constituídos por diferentes orientações de enatiômeros. A rara ocorrência de sistemas racêmicos em grupos espaciais não-centrossimétricos tornou este evento um caso notável. A partir das propriedades físico-químicas, os polimorfos puderam ser monotropicamente relacionados. Os resultados desta tese trazem importantes contribuições científicas para diversidade de formas sólidas e também define novas formulações sólidas para utilização como antidepressivos.
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Jury, Nicholas J. "Alterations in Peripheral and Central Serotonin Physiologies during Lactation: Relevance to Mood during the Postpartum Period." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1342729814.
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Nyandege, Abner. "ASSOCIATION BETWEEN CONCOMITANT USE OF BISPHOSPHONATES AND SEROTONIN REUPTAKE INHIBITORS AND INCREASED RISK OF OSTEOPOROTIC-RELATED FRACTURES: AMONG COMMUNITY-DWELLING POSTMENOPAUSAL WOMEN." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/557.
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Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs and SSRIs and fracture risk. Separate cross-sectional analyses were performed using data from the 2004-2008 Medical Expenditure Panel Survey (MEPS) and Medicare Part D prescriptions claims data (2008-2010) to examine usage patterns of BPs and SSRIs/SNRIs for women aged ≥45 years and ≥65 years, respectively. For our second objective, a nested-case control was conducted using Medicare claims data (2008-2010). Data from Medicare inpatient claims were linked to Medicare Part D data for all female BP users 65 years or older. We used Cox proportional hazards model to assess the increased risk of osteoporotic-related fractures among propensity score matched (1:1 ratio) cohorts of concomitant users of BPs and SSRIs and BP alone users. Concomitant use of BPs and SSRIs was prevalent and increased with age for each timeframe examined. Findings showed that approximately 12% (using MEPS) and 28% (using Medicare data) of women on BPs were also on SSRIs. For the second objective, 4,214 propensity score matched pairs (average age=80.4 years) of subjects were analyzed. Findings showed that concomitant use of BPs and SSRIs was associated with statistically significant increased risk for any fracture (HR=1.29, 95% CI, 1.07-1.57), but statistically non-significant increased risk for hip (HR=1.16, 95% CI, 0.92-1.47) and vertebral fractures (HR=1.55, 95% CI, 0.97-2.48). Current findings indicate that concomitant use of BPs and SSRIs is not uncommon among postmenopausal women and suggest potential attenuation of antifracture efficacy of BPs by SSRIs. Further studies are needed to understand the clinical impact of concomitant use of these medications among older postmenopausal women.
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Davidson, Jonathan R. T., Hans-Ulrich Wittchen, Pierre-Michel Llorca, Janelle Erickson, Michael Detke, Susan G. Ball, and James M. Russell. "Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder: A double-blind placebo-controlled trial." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-110320.
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The objective was to examine duloxetine 60–120mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥50% reduction in Hamilton Anxiety Rating Scale total score to ≤11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P≤0.001) and worsened on each outcome measure (P≤0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.
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Beesdo, Katja, James Hartford, James Russell, Melissa Spann, Susan Ball, and Hans-Ulrich Wittchen. "The short- and long-term effect of duloxetine on painful physical symptoms in patients with generalized anxiety disorder: Results from three clinical trials." Technische Universität Dresden, 2009. https://tud.qucosa.de/id/qucosa%3A26856.
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Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n = 840) were 9- to 10-week efficacy trials; study 3 (n = 887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0–100; n = 1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p ≤ 0.01). In study 3, pain symptoms worsened in responders switched to placebo compared with those maintained on duloxetine (p ≤ 0.02). In conclusion, duloxetine was efficacious in the short- and long-term treatment of PPS, which are common in GAD patients.
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Brooke, Elizabeth Cameron. "Waterborne Fluoxetine Exposure Disrupts Metabolism in Carassius auratus." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32253.
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Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI) and the active ingredient in Prozac®, is found in the environment and disrupts feeding and metabolism in exposed fish. The objective of this research was to investigate the mechanisms involved in the feeding and metabolism disruption in the model goldfish (Carassius auratus). Two short-term waterborne fluoxetine exposures (7- and 14-days) were performed using two environmentally relevant doses of fluoxetine (0.5 and 1 μg/L) and metabolic effects at the level of the brain, liver, serum and bile in goldfish were investigated. Abundances of mRNA transcripts coding for six feeding neuropeptides were examined to determine which may be involved in the initial neural changes associated with decreased appetite in goldfish. The 7-day fluoxetine exposure at 1 μg/L caused corticotropin-releasing factor (CRF) mRNA levels to increase by 2-fold in female hypothalamus and telencephalon, indicating that CRF may be one of the first of the feeding neuropeptides to be altered. Six hepatic miRNAs were also evaluated in the goldfish liver that were previously associated with fluoxetine exposure in zebrafish (Danio rerio). Following the 7-day exposure at 1 μg/L, miR-22b, miR-140, miR-210, miR-301a and miR-457b levels increased in the female goldfish liver by 4-6 fold. The 14-day fluoxetine exposure at 1 μg/L caused 2-fold increases in miR-210, miR-301a, miR-457b and let-7d in male goldfish liver. These miRNAs were associated with the down-regulation of anabolic metabolic pathways in zebrafish, indicating a conservation of miRNA and fluoxetine effect between fish species. Serum and bile metabolite profiles of fluoxetine exposed goldfish were evaluated using ultra performance liquid chromatography coupled to quadrupole time of flight mass spectrometry. Following the 14-day exposure at 1 μg/L, the bile metabolite profiles of male goldfish were significantly different from controls as detected by cluster analysis and fluoxetine was tentatively identified in the serum. No other discriminant metabolites were identified as of yet. The data presented suggest that fluoxetine causes metabolic disruption in goldfish at multiple organ levels. Because of the widespread detection of fluoxetine and other emerging SSRIs in the aquatic environment, future research is required to firmly establish this pharmaceutical class as a metabolic and endocrine disrupting chemical.
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Zhang, Ying [Verfasser]. "A systematic review of the efficacy and tolerability of selective serotonin reuptake inhibitors in the treatment of Chinese patients with depressive disorders / Ying Zhang." Ulm : Universität Ulm. Medizinische Fakultät, 2012. http://d-nb.info/1024931218/34.
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Davidson, Jonathan R. T., Hans-Ulrich Wittchen, Pierre-Michel Llorca, Janelle Erickson, Michael Detke, Susan G. Ball, and James M. Russell. "Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder: A double-blind placebo-controlled trial." Technische Universität Dresden, 2008. https://tud.qucosa.de/id/qucosa%3A26830.
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The objective was to examine duloxetine 60–120mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥50% reduction in Hamilton Anxiety Rating Scale total score to ≤11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P≤0.001) and worsened on each outcome measure (P≤0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.
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Ayad, Nancy B. "Effects of Antidepressants on Human Mesenchymal Stem Cell Differentiation on Clinically Relevant Titanium Surfaces." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4477.
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Selective Serotonin Reuptake Inhibitors (SSRIs) are the most frequently prescribed class of drugs worldwide and are implemented in the treatment of depression and other psychiatric disorders. SSRIs relieve depressive symptoms by modulating levels of the neurotransmitter serotonin in the brain. SSRIs block the function of the serotonin transporter, thereby increasing concentrations of extracellular serotonin. However, serotonin levels in the neurons of the brain only account for 5% while the remaining 95% is present outside the brain. Serotonin receptors and transporter are located on bone resident cells (mesenchymal stem cells (MSCs)), osteoblasts and osteoclasts, and serotonergic activity is believed to affect bone homeostasis. Consequently, alterations in serotonin levels by SSRI treatment have the potential to alter bone formation and remodeling. Clinical reports correlate increase risk of bone fractures and delayed bone healing with SSRI use. Metallic implants are commonly used as orthopedic and dental implants to fix bony defects. Surface modifications have been used to increase the level of bone to implant contact by controlling the differentiation of MSCs into an osteoblastic linage and facilitate bone production. However, it is not known if SSRIs can affect MSCs osteoblastic differentiation and bone remodeling signaling in response to microstructured biomaterials. The aims of this study were: 1) Investigate the effects of SSRIs on MSCs differentiation on microstructured titanium (Ti), 2) Determine the effects of SSRIs on bone remodeling signaling and osteoclast activation, and 3) Elucidate the effects of SSRIs on serotonin receptors and their effect on bone remodeling. To investigate this, human MSCs were grown on tissue culture polystyrene (TCPS), smooth Ti (PT) or microstructured Ti (SLA) surfaces under exposure to therapeutic concentrations of commonly prescribed antidepressants (SSRIs (fluoxetine, sertraline, paroxetine), Selective Norepinephrine Reuptake Inhibitor (SNRI) (duloxetine) and other regularly prescribed antidepressants (bupropion)) during differentiation toward osteoblasts. Osteoblastic differentiation was assessed in MSCs after treatment with the drugs (0.1μM, 1μM, 10μM) by alkaline phosphatase activity and osteocalcin levels. Antidepressant treatment decreased levels of MSC differentiation markers on microstructured Ti surfaces. Furthermore, treatment dose-dependently decreased protein levels secreted by MSCs which are important for bone formation (BMP2, VEGF, Osteoprotegerin), and increased those involved in bone resorption (RANKL). To determine the effect of SSRIs on bone remodeling signaling and osteoclast activation, human osteoclasts were either directly exposed to antidepressants or conditioned media obtained from MSCs treated with antidepressants on Ti surfaces, after which, enzymatic tartrate-resistant acid phosphatase (TRAP) activity was assessed. Antidepressants increased TRAP activity both directly and through treated MSCs, with the highest levels evident after treatment with conditioned media from MSCs on microstructured Ti surfaces. To elucidate the effects of serotonin receptors and their effect on bone remodeling, receptors were pharmacologically inhibited. Surface roughness decreased gene expression of HTR2A, HTR1B, and HTR2B, and antidepressant treatment increased their expression. Inhibition of HTR2A decreased RANKL protein levels, while inhibition of other serotonin receptors had no effect on RANKL or OPG levels. These studies suggest that antidepressants inhibit MSCs differentiation on microstructured Ti surfaces and increase levels of proteins associated with bone resorption. Additionally, our results showed that RANKL is regulated by serotonin receptor HTR2A. Taken together, our results suggest that antidepressants have a negative effect on osteoblastic differentiation, compromising bone formation and enhancing bone resorption, which can be detrimental to patients under orthopedic and dental treatment.
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Khalifa, Aseel. "En utvärdering av 5-HT1A-receptoragonisten vilazodone för en utökad antidepressiv effekt i behandlingen av egentlig depression." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-336781.
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Major depressive disorder (MDD) is a mood disorder majorly responsible for disability and mortality worldwide. With a lifetime prevalence of 15-20%, it is the main cause of functional impairment in Western societies as well as the fourth most debilitating illness in the world. Although the pathophysiology of MDD is not yet fully understood, some evidence that suggest the presence of a neuroanatomical deficiency have given rise to the theory of a specific imbalance in the monoamine neurotransmitters noradrenaline (NA) and/or serotonin (5-HT) levels in the brain. Overall, the various classes of antidepressant agents that have been developed to increase monoamine levels on the basis of this proposal have been successful. However, facts relating to prevalent escalation in the illness and recurring episodes of depression point towards a need to enhance clinical treatment. Most conventional antidepressants such as selective serotonin reuptake inhibitors (SSRI) and selective serotonin and noradrenaline inhibitors (SNRI) pose problems in symptomatic improvement. These include therapeutic lag, safety and tolerability issues, making more than 30% patients with MDD unable to reach adequate relief. In this respect, the action mechanism has moved beyond conventional SSRI and lead to the introduction of vilazodone, a novel antidepressant with an additional 5-HT1A partial agonist profile argued to be of potential benefit for a greater efficacy, faster onset of action and better tolerability. Using secondary data, this project aimed to evaluate the role of vilazodone as a SPARI-drug in the overall clinical treatment of MDD as well as its potential in addressing some of the most common obstacles in antidepressant treatment. Study results proved vilazodone’s efficacy to be superior to placebo. Patients across all studies showed significant improvement in depressive symptoms measured in MADRS and HAMD17. Vilazodone was also shown to be generally safe and tolerable but was not positively distinguished from placebo with regards to adverse effects. An overall, meaningful improvement in depressive symptoms was demonstrated in vilazodone, which reinforces its merit as an important treatment option for patients with MDD.
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Muatasim, Mustafa. "Effektivitet och säkerhet av tricykliska antidepressiva och selektiva serotonin-återupptagshämmare vid behandling av irritabel tarmsyndrom (IBS)." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-101916.
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Irritable bowel syndrome (IBS) is a functional disorder that affects the gastrointestinal tract and especially the large intestine. The pathogenesis of the disease is not fully understood, for that reason there is still no cure and current therapy focuses on symptom relief. The disease manifests itself in the form of abdominal pain, bloating, constipation or diarrhoea. New studies have shown a link between IBS and communication between the central nervous system and the gut. Serotonin and norepinephrine seem to be important for the course of the disease. The purpose of this literature review was to study the efficacy and safety of certain antidepressant preparations belonging to tricyclic antidepressants and selective serotonin reuptake inhibitors in the treatment of IBS. This work focused on the effect of preparations and how tolerable they are with respect to their side effects. Articles presented in this work were found in the PubMed database with the keywords "irritable bowel syndrome", "serotonin reuptake inhibitor", " tricyclic antidepressants ". Amitriptyline 10 mg and imipramine 25 mg provided a statistically significant symptom relief in IBS with diarrhoea (IBS-D) compared to placebo. In addition, tianeptine 12.5 mg 3 times / day, which belongs to the selective serotonin reuptake enhancer (SSRE) group, gave a corresponding symptom relief as amitriptyline 10 mg once / day. The difference between the two was not statistically significant, but the study was open label and non-placebo-controlled, which made it difficult to draw any conclusions. Fluoxetine, which belongs to the selective serotonin reuptake inhibitor (SSRI) group, produced a statistically significant effect compared to placebo in the treatment of constipation IBS (IBS-C). In contrast, paroxetine-CR did not have any statistically significant effect on abdominal pain in IBS-C compared with placebo. However, more patients in the paroxetine group achieved the secondary outcome (clinical global improvement) with scores of 1-2 on the scale Clinical Global Impressions-Improvement (CGI-I). Based on the studies presented in this literature study, it is concluded that a low dose of TCA is an effective and safe treatment for IBS-D while SSRIs are effective and safe in the treatment of IBS-C compared to placebo.Irritable bowel syndrome (IBS), är funktionella störningar som drabbar gastrointestinalkanalen och framför allt kolon. Patogenesen till sjukdomen är inte helt klarlagd, av den anledningen saknas fortfarande någon botande behandling och dagens terapi fokuserar på symtomlindring. Sjukdomen yttrar sig i form av buksmärta, uppblåsthet, förstoppning eller diarré. Senaste studier har visat en koppling mellan IBS och kommunikation mellan centrala nervsystemet och tarmen. Serotonin och noradrenalin verkar ha betydelse för sjukdomsförlopp. Syftet med detta litteraturarbete var att studera effektivitet och säkerhet för några antidepressiva preparat som tillhör tricykliska antidepressiva och selektiva serotonin återupptagshämmare vid behandling av IBS. Detta arbete fokuserade på effekten av preparaten och hur tolererbara de är med avseende på deras biverkningar. Artiklar som presenteras i detta arbete söktes i databasen Pubmed med sökord ”irritable bowel syndrome”, ”serotonin reuptake inhibitors”, ” tricyclic antidepressants”. Amitriptylin 10mg och imipramin 25mg gav en statistiskt signifikant symtomlindring vid IBS med diarré (IBS-D) jämfört med placebo. Dessutom gav tianeptin 12,5mg 3 gånger/dag, som tillhör läkemedelsgruppen selektiv serotonin återupptagsenhancer (SSRE), en likvärdig symtomlindring som amitriptylin 10mg en gång/dag. Skillnaden mellan de två var inte statistiskt signifikant, däremot var studien openlabel och icke-placebokontrollerad vilket gör det svårt att dra någon slutsats. Fluoxetin, som tillhör läkemedelsgruppen selektiva serotonin återupptagshämmare SSRI, gav en statistiskt signifikant effekt jämfört med placebo vid behandling av IBS med förstoppning (IBS-C). Däremot gav paroxetin-CR ingen statistiskt signifikant effekt på buksmärta vid IBS-C jämfört med placebo, dock uppnådde fler i paroxetingruppen den sekundära utfallsvariabeln (global klinisk förbättring) och fick poäng mellan 1 – 2 på skalan Clinical Global Impressions-Improvement (CGI-I). Baserat på studierna som presenteras i denna litteraturstudie dras slutsatsen att en låg dos TCA är en effektiv och säker behandling vid IBS-D medan SSRI är effektiva och säkra vid behandling av IBS-C jämfört med placebo.
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Salazar, Fernanda Rodrigues. "Determinação de fármacos antidepressivos em leite materno." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/159544.
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O uso de fármacos durante a lactação é uma prática comum; porém, os tratamentos farmacológicos impõem grandes dúvidas tanto aos profissionais quanto às nutrizes sobre a segurança do uso destes durante este período. A amamentação é uma forma de vínculo entre mãe e bebê e está associada a diversos benefícios nutricionais, imunológicos, cognitivos, psicoafetivos, econômicos e sociais. A depressão é um problema clínico importante durante o período pós-parto, e a vulnerabilidade para o início ou recorrência de sintomas depressivos aumenta a possibilidade de uso de psicofármacos enquanto ocorre a lactação. Os antidepressivos inibidores seletivos da recaptação da serotonina são comumente prescritos para o tratamento destes quadros depressivos, entre eles fluoxetina, sertralina, citalopram e paroxetina, sendo que a maioria destes é excretada no leite materno e há grande variabilidade na quantidade de analitos que pode ser recebida pelo lactente. Bupropiona é um fármaco antidepressivo utilizado para o tratamento do tabagismo e quadros depressivos e tem sua excreção ao leite materno relatada em literatura. Métodos bioanalíticos para determinação da excreção de fármacos antidepressivos foram desenvolvidos e validados por cromatografia líquida acoplada a espectrômetro de massas e cromatografia líquida com detecção ultravioleta. Estes métodos demonstraram serem seletivos, lineares, precisos e exatos, com limites de quantificação de 5 ng/mL (fluoxetina, citalopram e bupropiona) e 20 ng/mL (sertralina e paroxetina) para método por LC-MS e de 200 ng/mL para todos os analitos no método por CLAE-UV. As amostras de leite materno foram coletadas em Banco de Leite de mães que declararam utilizar fluoxetina ou sertralina ou paroxetina e analisados. Os dados de concentração encontrados para os fármacos referidos estão dentro da faixa encontrada em literatura confirmando sua excreção no leite materno. Paroxetina apresentou valores abaixo do limite de quantificação. Das concentrações encontradas no leite materno, foram estimadas as doses absolutas e relativas no lactante, sendo que os resultados demonstraram baixos valores em relação a estas estimativas, podendo os fármacos analisados ser considerados seguros para manutenção do uso durante a lactação. Foi também detectada nas análises por LC-MS a presença de norfluoxetina, metabólito da fluoxetina, confirmando sua excreção nesta matriz.The use of medications during lactation is a common practice; however pharmacological treatments impose serious doubts to both, professionals and nursing mothers, about the safety of drugs use during this period. Breastfeeding is a natural form of bonding between mother and baby and it is associated with many nutritional, immunological, cognitive, psychoemotional, social and economic benefits. Depression is a major clinical problem during the postpartum period and the vulnerability to onset or recurrence of depressive symptoms increases the possibility of psychotropic drug use during lactation. Selective inhibitors of serotonin reuptake are commonly prescribed for the treatment of depressive disorders, including fluoxetine, sertraline, citalopram and paroxetine. Most of these drugs are excreted in breast milk and there is great variability in the amount of analytes that can be received by the infant. Bupropion is an antidepressant used for tabagism treatment and for depression symptoms; it is also described in literature its excretion into breast milk. Bioanalytical methods for determining the excretion of antidepressants were developed and validated by liquid chromatography coupled to mass spectrometry and liquid chromatography with ultraviolet detection. These methods proved to be selective, linear, precise and accurate with quantification limits of 5 ng/mL (fluoxetine, citalopram e bupropion) and 20 ng/mL (sertraline e paroxetine) for LC-MS method and 200 ng/mL for all analytes in the CLAE-UV method. Human milk samples were collected in milk banks from mothers to which the antidepressants fluoxetine or sertraline or paroxetine were administered, and the concentrations in this matrix were verified. Found concentrations were within the range described in the literature confirming their excretion in the breast milk. Paroxetine presented values less than limit of quantification. From the found concentrations, the absolute and relative doses in nursing were estimated. The results showed low values for these estimates and so the analyzed drugs can be considered safe to continue use during lactation. The presence of norfluoxetine, a metabolite of fluoxetine, was also detected by LC-MS, confirming its excretion in this matrix.
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Alvaia, Clarissa Gomes Andrade. "Efeito da administração de cloridrato de fluoxetina em ratos submetidos a um modelo de parkinsonismo induzido por reserpina." Pós-Graduação em Ciências Fisiológicas, 2017. http://ri.ufs.br/jspui/handle/riufs/7404.
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Parkinson`s Disease is the second most common motor disorder and is also considered a progressive multisystemic disease associated to several nom motor symptoms (NMS), such as depression, with a prevalence of about 50% among PD patients. Selective serotonin reuptake inhibitors (SSIR) are the main treatment for this NMS, although researches with acutely induced parkinsonism has related fluoxetine to increased motor impairment. The aim of the present research is to evaluate the effect of the fluoxetine hydrochloride on a model of parkinsonism induced by low doses of reserpine. Sixty-four male 7-9-month-old Wistar rats were used, and were obtained from vivarium of the Department of Physiology – Federal University of Sergipe. Animals were divided into four groups: fluoxetine vehicle + reserpine vehicle (CTR); fluoxetine 10 mg/kg + reserpine vehicle (F); fluoxetine 10 mg/kg + reserpine 0,1 mg/kg (F + R); and fluoxetine vehicle + reserpine 0,1 mg/kg (R). During the treatment, the animals were submitted to open field test, catalepsy test and tremoulous jaw movement evaluation. It was shown that animals treated with fluoxetine and reserpine spent more time at the catalepsy test, decreased distance travelled, lower number of rearing at the open field test, increased tremulous jaw movements and increased weight loss. The treatment only with fluoxetine caused immunohistochemistry changes, such as decrease of TH expression in the dorsal striatum and increased staining of the dorsal raphe nucleus, with no correlation with MS for this group. The F + R group showed different immunohistochemistry results for both acute and continued administrations.A Doença de Parkinson (DP) é a segunda desordem motora mais comum e também é considerada uma doença progressiva multissistêmica ligada a vários sintomas não motores (SNM), como a depressão, que acomete cerca de 50% dos pacientes. Os inibidores seletivos da recaptação de serotonina (ISRS) são considerados os principais medicamentos para o tratamento desse SNM, embora pesquisas que utilizaram indução aguda de parkinsonismo tenham relacionado a fluoxetina ao agravamento dos sintomas motores. Diante disso, este estudo objetivou avaliar o efeito da administração de cloridrato de fluoxetina em um modelo de parkinsonismo induzido por baixas doses de reserpina. Foram utilizados 64 ratos Wistar, machos, com idade de 7 a 9 meses, provenientes do Biotério Setorial do Departamento de Fisiologia da Universidade Federal de Sergipe. Os animais foram divididos aleatoriamente em quatro grupos: veículo fluoxetina + veículo reserpina (CTR); fluoxetina 10 mg/kg + veículo reserpina (F); fluoxetina 10 mg/kg + reserpina 0,1 mg/kg (F + R); e veículo fluoxetina + reserpina 0,1 mg/kg (R). Durante o tratamento, os animais foram submetidos aos testes de campo aberto, catalepsia e avaliação dos movimentos orofaciais. Foi observado aumento da latência na barra, diminuição da distância total percorrida em campo aberto, diminuição do número de rearing, aumento dos movimentos involuntários de mandíbula e maior alteração de peso corporal dos animais do grupo F + R. O tratamento apenas com fluoxetina provocou alterações imunohistoquímicas, como a diminuição da expressão de TH no estriado dorsal e aumento da marcação para 5-HT no núcleo dorsal da rafe, sem correlação com nenhum sintoma motor para esse grupo. O grupo F + R apresentou resultados de imunorreatividade distintos para as administrações breve e continuada.
São Cristóvão, SE
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Silva, Silvana Maciel. "Padronização e validação do método extração sortiva em barra de agitação e cromatografia líquida de alta eficiência (SBSE/HPLC) para a determinação de antidepressivos em amostras de plasma." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-24052007-101018/.
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A monitorização terapêutica permite a individualização do regime de dosagem, assegurando a eficácia clínica e minimizando os efeitos adversos dos fármacos, prescritos na clínica. Os antidepressivos têm sido monitorados, pois, apresentam intervalos terapêuticos bem estabelecidos, ou seja, a maioria dos pacientes, que apresentam concentrações plasmáticas dentro deste intervalo fixo, tem as desordens psiquiátricas mantidas sob controle e efeitos adversos aceitáveis. Os antidepressivos tricíclicos (ADTs): imipramina, amitriptilina, nortriptilina e desipramina, embora eficazes e ainda muito utilizados, apresentam efeitos adversos, não desejáveis. Os antidepressivos, inibidores seletivos da recaptação de serotonina (ISRSs): citalopram e sertralina, apresentam eficácia clínica comparável aos clássicos ADTs, mas destituídos dos efeitos adversos associados aos mesmos. Os métodos convencionais, empregados no tratamento de amostras biológicas, para análises de antidepressivos por técnicas cromatográficas, têm sido a extração líquido-líquido e extração em fase sólida. A extração sortiva em barra de agitação (SBSE), técnica recente de preparo de amostras para a préconcentração de compostos orgânicos presentes em amostras biológicas, baseiase na extração estática, através do polímero polidimetilsiloxano (PDMS), no qual ocorre a dissolução (sorção, partição) do analito. Neste trabalho, as técnicas SBSE e cromatografia líquida de alta eficiência foram avaliadas para a análise simultânea dos antidepressivos em amostras de plasma para fins de monitorização terapêutica. As condições cromatográficas de análise, assim como as variáveis SBSE de extração (tempo, temperatura, força iônica, pH da matriz) e tempo de dessorção, foram otimizadas, visando adequada sensibilidade analítica. A validação analítica foi realizada segundo normas da ANVISA, em diferentes concentrações plasmáticas, as quais contemplam o intervalo terapêutico. O método SBSE/HPLC padronizado apresentou linearidade na faixa de concentração plasmática de 20 a 1000 ng mL-1, precisão interensaio com coeficientes de variação menor que 14% e recuperação relativa de 83 a 110%. Segundo a validação analítica, a metodologia SBSE/HPLC apresentou linearidade, alta sensibilidade, seletividade e precisão analítica adequadas para a análise dos antidepressivos: imipramina, amitriptilina, nortriptilina, desipramina, citalopram e sertralina, em amostra de plasma, para fins de monitorização terapêutica.Therapeutic drug monitoring allows individualization of drug dosage assuring its clinical efficacy and at the same time minimizing adverse effects of the drugs prescribed in clinics. The antidepressants have been monitored since they present a very well established therapeutic interval. In this sense, most of the patients whose plasmatic concentrations are ranged at that interval present psychiatric disorders under control and drug adverse effects at bearable levels. Despite tricyclic antidepressants (TCAs) such as imipramine, amitriptyline, nortriptyline and desipramine are highly efficient and widely used, they also present undesirable adverse effects. The antidepressants: citalopram and sertraline, which are selective serotonin reuptake inhibitors (SSRIs), present clinical efficacy comparable to the classic TACs, but with no adverse effects associated to the last ones. Liquid-liquid extraction (LLE) and solid phase extraction (SPE) have been usually employed in biological sample pre-treatment for chromatographic analysis. A new technique named sorptive stir bar extraction (SBSE) for sample pre-concentration of organic compounds from biological samples was recently proposed. This technique is based on static extraction through the polymer polidimetilsiloxane (PDMS), in which analyte sorption occurs. In this work, SBSE and HPLC techniques have been evaluated for out antidepressants simultaneous analysis in plasma samples for therapeutic drug monitoring. The chromatographic conditions of analysis, as well as SBSE parameters (time, temperature, ionic strength, matrix pH, desorption time) have been optimized in order to obtain best analytical sensitivity. Analytical validation was carried out according to the norms established by ANVISA, in different plasmatic concentrations, which represent the therapeutic interval. The SBSE/HPLC method developed showed linearity in a concentration plasmatic ranging from 20 to 1000 ng mL-1, inter assay precision with coefficient of the variation lower than 14%, and relative recovery from 83 a 110%. Based on analytical validation, the SBSE/HPLC methodology showed good linearity, high sensitivity, selectivity and suitable repeatability to the analyzed antidepressants: imipramine, amitriptyline, nortriptyline, desipramine, citalopram and sertraline in plasma samples for therapeutic drug monitoring.
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Lobo, Sandra Daniela Gouveia Paiva. "Novas abordagens farmacológicas no tratamento da depressão." Master's thesis, 2016. http://hdl.handle.net/10284/5928.
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A depressão é uma doença do foro psicológico que se caracteriza pela presença de humor deprimido, perda de interesse ou prazer, pensamentos suicidas, tristeza súbita, ansiedade, irritabilidade e baixa auto-estima. As causas que levam ao seu aparecimento ainda não se encontram totalmente esclarecidas, no entanto várias teorias apontam para alterações morfológicas a nível cerebral causadas pelo défice de monoaminas.
Segundo dados revelados pela Organização de Saúde (OMS) a depressão tem aumentado drasticamente nos últimos anos e estima-se que em 2020 seja a segunda doença mais prevalente a nível mundial apenas ultrapassada pelas doenças cardiovasculares, assim com este aumento exponencial dos transtornos depressivos também o consumo de antidepressivos aumentou, cerca de 25,4% nos últimos 5 anos.
Os primeiros fármacos antidepressivos foram descobertos acidentalmente sendo eles os antidepressivos tricíclicos e os inibidores da monoaminoxidase, estes fármacos tornaram possível o tratamento da depressão, no entanto devido à falta de seletividade e à interação com certos alimentos tornaram estas classes de antidepressivos um tratamento de segunda linha uma vez que provocam vários efeitos adversos graves podendo mesmo originar a morte do paciente.
Devido aos vários efeitos secundários dos primeiros antidepressivos utilizados, surgiram novas classes farmacológicas para o tratamento da depressão de forma a proporcionar um tratamento igualmente eficaz mas sem os indesejáveis efeitos adversos dos primeiros antidepressivos sendo eles, os Inibidores Seletivos de Recaptação de Serotonina (ISRS) e Inibidores Seletivos da Recaptação de Serotonina e Noradrenalina (ISRSN), estes segundos têm uma maior seletividade para os recetores responsáveis pelo aparecimento da depressão, no entanto devido ao facto de a depressão ser uma doença do foro psicológico, diferentes pessoas reagem de modo diferente a cada fármaco. Atualmente, os mais recentes fármacos antidepressivos são mais eficazes, têm menos efeitos colaterais, menor tempo de latência e diferentes mecanismos de ação do que os seus antecessores.
Nas mais recentes abordagens farmacológicas no tratamento da depressão encontram-se fármacos como o escitalopram (ISRS), a duloxetina (ISRSN), a reboxetina considerada um potente inibidor da recaptação de noradrenalina (ISRN), o bupropiom que é o único inibidor seletivo de recaptação de dopamina e noradrenalina e a agomelatina que é talvez o fármaco com o mecanismo de ação mais inovador e diferente de todos os outros pois não atua a nível das monoaminas mas sim na regulação do ciclo circadiano e por isso é considerado um antidepressivo melatoninérgico. Todos estes antidepressivos atualmente usados têm a sua eficácia comprovada no tratamento da depressão e os seus benefícios/riscos serão abordados posteriormente.
A elaboração deste trabalho de revisão bibliográfica foi elaborada através de uma pesquisa sobre o tema, através de várias publicações científicas, livros da especialidade e monografias.Depression is a disease of the psychological conditions characterized by the presence of depressed mood, loss of interest or pleasure, suicidal thoughts, sudden sadness, anxiety, irritability and low self-esteem. The causes that lead to their appearance are not yet fully understood but several theories point to morphological changes in the brain caused by monoamine deficit. According to figures released by the Health Organization (WHO) depression has increased dramatically in recent years and it is estimated that in 2020 is the second most prevalent disease in the world surpassed only by cardiovascular disease, so with this exponential increase in depressive disorders also antidepressants increased consumption, according to the WHO revealed the consumption of antidepressants increased 25.4% in the last 5 years. The first antidepressants were accidentally discovered they are tricyclic antidepressants and monoamine oxidase inhibitors, this drug became possible to treat depression, however due to lack of selectivity and interaction with certain foods currently these antidepressants are second-line treatment one as they cause various serious adverse events may even lead to the death of the patient. Owing to various side effects of the first new antidepressant drug classes used arisen for the treatment of depression in order to provide an equally effective treatment without undesirable side effects of the first antidepressants them being selective serotonin reuptake inhibitors (SSRIs) and Selective Inhibitors reuptake of serotonin and norepinephrine (SNRIs), these latter have greater selectivity for receptors responsible for the onset of depression, however due to the fact that depression is a disorder of psychological conditions different people respond differently to each drug. Currently the latest antidepressants are more effective, have fewer side effects, shorter latency and different mechanisms of action than its predecessors. In recent pharmacological approaches to treat depression are drugs such as escitalopram (SSRI), duloxetine (SNRI), reboxetine considered a potent norepinephrine reuptake inhibitor (SNRI), bupropion which is the only selective reuptake inhibitor and noradrenaline and dopamine agomelatine is perhaps the most innovative drug-action mechanisms and different from all others because it has no effect on the level of monoamines but in the regulation of the circadian cycle and is therefore considered a melatoninergic antidepressant. All these antidepressants currently used have proven effective in treating depression and its benefits / risks will be discussed later. The preparation of this work of literature review was prepared through a search on the subject, through various scientific publications, specialty books and monographs.
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Wedmann, Fabian. "Psychopharmaka und das Risiko von Stürzen in der stationären geriatrischen Versorgung." Doctoral thesis, 2019. http://hdl.handle.net/21.11130/00-1735-0000-0003-C193-C.
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Mathebe, Ntlatseng Gretta Rhoda. "Fabrication and kinetic modeling of cytochrome P450 2D6 amperometric biosensors for serotonin reuptake inhibitors." Thesis, 2005. http://etd.uwc.ac.za/index.php?module=etd&.
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Salkeld, Erin Samantha Marie. "The risk of postpartum haemorrhage (PPH) with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants." 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=450634&T=F.
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Peterson, Lori J. "Selective Serotonin Reuptake Inhibitors and Bone Mineral Density in a Population of U. S. Premenopausal Women." 2011. https://scholarworks.umass.edu/theses/633.
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Selective Serotonin Reuptake Inhibitors and Bone mineral Density in a Population of U.S. Premenopausal Women
May 2011
M.S., UNIVERSITY of Massachusetts Amherst
Directed by: Professor Elizabeth R. Bertone-Johnson
Low bone mineral density (BMD) in post-menopausal women is a risk factor for bone fractures and osteoporosis development. Prior studies in post-menopausal women have shown the use of antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) to be inversely related to BMD. However, the association has not been studied in pre-menopausal women. Current SSRI use is widespread with 8% of U.S. women age 18-44 reporting use. We evaluated the association between SSRIs and BMD and bone mineral content (BMC) cross-sectionally using data from the University of Massachusetts Vitamin D Status Study. SSRI use, diet, and lifestyle factors were assessed by questionnaire. BMD and BMC were measured using dual-energy x-ray absorptiometry (DEXA). The study included 256 women aged 18-30 (mean=21.6 years, SD=4.3 years). In this population, SSRI use was 5%, BMD values ranged from 0.97-1.38 g/cm2 (mean 1.16, SD 0.08), and BMC values ranged from 1833g to 3682g (mean 2541.5, SD=349.2). After adjustment for age, body mass index, and physical activity, mean BMD in the 13 users of SSRIs was 1.15g/cm2 (SD=0.06) compared to 1.16g/cm2 (SD=0.77) in the 243 non-users (p =0.66). After the same adjustments, mean BMC in the 13 users was 2467.1g (SD=285.0) compared to 2547.6g (SD=352.6) in the 243 non-users (p=0.94). Our findings do not support an inverse association between SSRI use and BMD or BMC. However, given the prevalence of SSRI use in young women and the potential for adverse effects on bone health, further study of this association is warranted.
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Armstrong, Hilary Farrar. "An investigation into the use of selective serotonin reuptake inhibitors for improving low lung function and pulmonary exacerbations." Thesis, 2018. https://doi.org/10.7916/D8CR79GP.
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Chronic obstructive pulmonary disease (COPD) is characterized by periodic episodes of worsening symptom (e.g., shortness of breath, irregular breathing, and worse coughing with increased phlegm production), also called pulmonary exacerbations. Inflammation is an important cause of reduced lung function as inflammation contributes to airflow obstruction in the small airways and lung parenchyma. Even in individuals with mild COPD, inflammation reduces lung function, accelerates decline in lung function overtime, and increases the risk for respiratory exacerbations. Agents that reduce systemic inflammation are hypothesized to decrease the inflammation in the lungs, resulting in improvements in lung function and a decrease in exacerbation frequency. We hypothesize that antidepressants have a beneficial effect on lung function. In addition to having anti-inflammatory properties, antidepressants act upon serotonin, which is integral in central breathing control. The combination of the anti-inflammatory and serotonergic effects may provide users of selective serotonin reuptake inhibitors with a lung function benefit while avoiding the side effects of steroids. This dissertation assesses whether selective serotonin reuptake inhibitors increase concurrent lung function and reduce the risk for respiratory exacerbations. It consists of three parts: a systematic literature review and two analytic papers using large prospective databases. The systematic review of the literature identified limitations concerning the effect of selective serotonin reuptake inhibitors on lung function. Overall, the analytic papers found no support for a beneficial association between selective serotonin reuptake inhibitors and spirometry, dyspnea or pulmonary exacerbations; indeed the association was in the opposite direction as hypothesized. In addition, there was no support for meaningful mediation by inflammatory markers. Further research is needed to determine if selective serotonin reuptake inhibitors have a harmful effect on lung function and pulmonary exacerbations.
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Kim, John. "Pharmacokinetics and pharmacodynamics of the selective serotonin reuptake inhibitors, fluoxetine and paroxetine, during pregnancy and the nursing period." Thesis, 2000. http://hdl.handle.net/2429/13088.
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The prevalence of depressive disorders during pregnancy and the postpartum period and the need for continuous pharmacological intervention necessitate a better understanding of antidepressant disposition via placental transfer and breast-feeding. However, there is relatively limited information available for pharmacokinetics of these drugs. In the present studies, the pharmacokinetics of fluoxetine and paroxetine were examined and compared in humans and sheep. In order to characterize drug disposition, several sensitive analytical methods for quantitative determination of fluoxetine and norfluoxetine isomers and paroxetine were developed using GC/MS and LC/MS/MS. In humans and sheep, fluoxetine and norfluoxetine cross the placenta extensively. A relatively lower fetal-to-maternal ratio of paroxetine compared to fluoxetine was observed in humans. In adults, fluoxetine is extensively metabolized; however, minimal metabolic capacity was observed in human and ovine fetus. In the fetal lamb, no detectable concentrations of norfluoxetine isomers were observed in fetal plasma and amniotic fluid following fetal fluoxetine administration. Limited accumulation of fluoxetine in amniotic fluids was observed in fetal lamb unlike other basic amine drugs. In humans, serum neonatal fluoxetine and norfluoxetine concentrations were remained elevated following birth and slowly declined. These data were consistent with an in vitro metabolism study in sheep, which indicated lack of fetal N-demethylation in contrast to adult microsomes. In contrast, neonatal paroxetine concentration declined rapidly following birth. In fetal lambs, moderate transient changes in blood gas status were observed following fluoxetine administration. However, in both fluoxetine- and paroxetine-exposed human gravida, neither significant changes in birth-outcome nor perinatal complications were observed. Fluoxetine, norfluoxetine and paroxetine are excreted in human breast milk with the milk-toserum ratio higher for fluoxetine compared to paroxetine, which resulted in relatively higher exposure to fluoxetine in combination with relatively lower metabolic capacity in the neonate. Serum drug concentrations were also measured in nursing infants, and detectable levels of fluoxetine and norfluoxetine were observed in infants younger than 2 months. Compared to adult ewes, significant changes in total body clearance, half-life and steadystate volume of distribution were observed in pregnant ewes. In addition, the stereoselective disposition of fluoxetine isomers was observed in both humans and sheep. In sheep, stereoselective pharmacokinetics following a single dose are mainly mediated by stereoselective plasma protein binding. However, during chronic therapy, stereoselective drug metabolism along with fluoxetine-mediated inhibition of hepatic enzymes is responsible for stereoselectivity. Clearance- and exposure time-dependency of stereoselective disposition was observed in both species. Therefore, stereoselectivity during chronic dosing may be mediated by the inhibition of CYP2D6 by fluoxetine and norfluoxetine and stereoselective metabolism of fluoxetine by CYP2C9/19. In conclusion, the present studies present the first detailed pharmacokinetics of fluoxetine and paroxetine during pregnancy and the nursing period, which suggest relatively lower exposure of paroxetine compared to fluoxetine. Furthermore, stereoselective disposition of fluoxetine was examined during both acute and chronic administration, and potential mechanisms were proposed.
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Yu, Yung-Mie, and 于永宓. "Effectiveness and Tolerability of Selective Serotonin Reuptake Inhibitors (SSRIs) versus Tricyclic Antidepressants (TCAs) in Depression Disorders: A Meta-analysis." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/89770298712021720696.
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碩士高雄醫學大學
藥學研究所碩士在職專班
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Background: Tricyclic antidepressants (TCAs) have been considered as one of the pharmacological treatments of depression. However, the newly marketed selective serotonin reuptake inhibitors (SSRIs) are generally though to have better efficacies and fewer side effects clinically than TCAs. Objectives: The purpose of this study was to compare the relative efficacies and tolerability of SSRIs and TCAs using meta-analysis. Methods: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers, MEDLINE, EMBASE, SDOS, PubMed, and JAMA. The literature search also included American Chemical Society, and New England Journal of Medicine which were from the database. Most of randomized controlled trials were included in this study. Study participants could include both genders and any age range with a primary diagnosis of depression. Data collected from each study included proportion of responders or drop-outs due to side effect and ineffectiveness. A series of meta-analyses of regarding therapy efficacies and side effects were performed using Review Manager v.4.2.6. Heterogeneity of treatment effect was considered. Results and Discussion: Thirty-eight trials were finally selected and contributed data to the meta-analysis of the relative efficacy of SSRIs and TCAs. Analysis of efficacy of drug therapy in depression resulted from 16,186 patients treated with SSRIs; 12,125 patients treated with TCAs. TCAs could be a better choice for patients with severe or major depression (odds ratio 0.89, 95% CI= [0.82, 0.97], p = 0.009). Drug efficacy in dysthymia control significantly favored in SSRIs (odds ratio 1.39, 95% CI= [0.88, 2.22], p = 0.16), although less drop-out rate for SSRIs therapy group was observed than that of TCAs (odds ratio 0.83, 95% CI= [0.77, 0.89], p<0.00001). The total drop-outs due to inefficacy for SSRIs was higher than that of TCAs (odds ratio 1.13, 95% CI= [1.05, 1.21], p = 0.0008). In the aspect of side effects, drop-out rate due to side effects for SSRIs was lower than that of TCAs (odds ratio 0.65, 95% CI= [0.61, 0.70], p<0.00001). Conclusions: Even though there are significant differences in efficacies of drug therapy for patients with major-depression between SSRIs and TCAs that is favor TCAs. SSRIs do appear to show an advantage over TCAs in terms of total drop-outs.
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Björklund, Aksoy Simon. "Effects of serotonin on personality in field crickets (Gryllus bimaculatus)." Thesis, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-138521.
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Animal personality can be defined as a set of physiological and behavioral characteristics that differ between individuals, but are consistent over time and across situations. The evolution of individual differences in behavior that are consistent over time and situations is still not clear. Our understanding of why animals have personality can be improved by investigating the underlying physiological mechanisms of animal behavior. Serotonin is a key monoamine that serves as a physiological modulator of animal behavior. Selective serotonin reuptake inhibitors are a group of chemicals that increase levels of serotonin in the brain. Fluoxetine is one such chemical and is used to treat depression in humans. In the field cricket (Gryllus bimaculatus), increased levels of serotonin have been linked to higher activity and boldness, which are both personality traits. In the current study, the effects of induced serotonin on activity, exploration, boldness and aggression was investigated. My results show that injecting fluoxetine causes substantial changes in behavioral traits used to describe personality in field crickets. This result is opposite to previous studies, as serotonin induced individuals were less active, less explorative, and won less fights, compared to control individuals. This could be due to serotonin existing naturally within the circulatory system of the field cricket, whereas fluoxetine is a manufactured chemical intended for human receptors, or that fluoxetine has a similar effect in modulating personality in field crickets as in humans. Since fluoxetine acts similarly in field crickets as in humans, an increased understanding of the effects of induced serotonin on different behaviors in field crickets could be beneficial for treating psychological illnesses.
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Fonseca, Marta Pereira Torres Lopes da. "The Use of Topical Emulsions containing Serotonergic Drugs to Modulate Skin Inflammation." Master's thesis, 2020. http://hdl.handle.net/10362/111473.
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Psoriasis is a chronic, immune, and inflammatory skin disease characterized by the appearance of localized or generalized erythematous plaques on the skin. Currently there are several treatments, however, the use of topical treatments is often a challenge due to several factors such as the low rate of penetration of the drug into the skin, the necessary complementation with other treatments and the low adherence by patients. In this sense, this dissertation focused on the development of a topical treatment, namely the development of an oil-in-water (O/W) emulsion with physical-chemical and sensory characteristics appealing to the consumer and capable of performing the desired therapeutic function through the incorporation of antidepressant drugs of the selective serotonin reuptake inhibitor (ISRS) type. Thus, after pre-formulation studies, O/W emulsions prepared by a cold emulsification process were developed, optimized, and characterized. Different solvents were studied as well as the influence of different preservatives in the final properties of the O/W emulsions. The developed emulsions were characterized and selected through rheological tests, droplet size distribution tests and microscopy analysis. After the development of the emulsion (placebo), in vitro and in vivo tests were performed for the selection of the drug to be incorporated. Antidepressants drugs, such as, fluvoxamine maleate, escitalopram oxalate and sertraline hydrochloride were studied, and fluvoxamine maleate was selected because it presents more promising results in the improvement of psoriatic symptoms. The incorporation of fluvoxamine maleate led physical instability of the selected emulsion. Thus, it was necessary to change the composition of the emulsion until reaching physical stability, incorporating the HPMC polymer and replacing the agent thickening with Sepineo™ P 600. The physicochemical characterization of the final emulsion with or without fluvoxamine maleate, as well as the rheological behaviour and the microstructure analysis were part of the study. Both formulations present suitable topical physicochemical properties. In vivo biological efficacy (hydration, TEWL and moisture evaluation) and sensorial analysis were performed on placebo final emulsion. The application of placebo for 28 days improved the hydration and the skin barrier, and the results of sensorial analysis confirmed a good consumer acceptability. In conclusion, it was possible to develop an O/W emulsion containing an antidepressant drug, with the desired and appealing characteristics for possible consumers and with promising biological and therapeutic efficacy.
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Dvořáčková, Vendula. "Postoje pacientů k léčbě antidepresivy." Master's thesis, 2013. http://www.nusl.cz/ntk/nusl-325140.
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Vendula Dvořáčková Attitudes of patients toward antidepressant medication Master's thesis Charles University in Prague, the Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Pharmacy Background: The master's thesis deals with evaluation of attitudes of inpatients in the psychiatric clinic of Military University Hospital Prague. The main task was to clarify the relation between therapy attitude and the prescribed medication, diagnosis and sociodemographic characteristics. Methods: The data were collected using the Drug Attitude Inventory questionnaire (Czech version by Masopust) where sum of negative and positive answers was used to determine the patient's general attitude. Patients' characteristics were acquired from a data-entry form, specific medication from the medical records. Results: In the observed group women seemed to have a more positive attitude toward the treatment compared to men, similarly to people with a higher level of education and patients between 31 - 40 years of age in comparison with other age groups. The most positive responses were observed in patients who were prescribed agomelatine, trazodone and paroxetine. People diagnosed with personal disorders or affective bipolar disorder inclined to positive answers as well, on the other hand most negative...
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Padilla, Eimeira. "Network mechanisms underlying susceptibility to helplessness and response to the antidepressant fluoxetine." Thesis, 2010. http://hdl.handle.net/2152/ETD-UT-2010-05-1054.
Full textAbstract:
Depression and post-traumatic stress disorder are common psychiatric comorbidities related to stress. These conditions are frequently treated with antidepressants such as selective serotonin reuptake inhibitors (SSRI’s). However, there are individual differences in susceptibility to stress-induced psychopathologies and response to antidepressants. Therefore, there is a need to identify biologic factors that predict vulnerability to stress and response to treatment. Furthermore, few studies have examined the neural correlates of antidepressant treatment response in a stress-susceptible animal model. This dissertation had three specific aims: 1) to characterize behavioral predictors of stress vulnerability by studying three dimensions of temperament (reward dependence, novelty-specific activity and harm avoidance) before stress exposure using a stress-susceptible rat strain, 2) to identify the neural network effects of response and non-response to SSRI treatment using a stress-susceptible animal model, and 3) to determine the neurophysiologic correlates of helplessness susceptibility. This was examined via measurement of regional brain metabolic capacity and functional connectivity within relevant neural circuits, and measurements of corticosterone and heart rate. These effects were studied in rats that underwent inescapable shock exposure followed by escape testing. Holtzman rats showed greater predisposition to helpless behavior following inescapable shock compared to Sprague Dawley and Long-Evans strains. Also, increased activity in a novel environment and low heart rate appeared to be markers of helplessness susceptibility in Holtzman rats. Limbic-cortical network effects were identified that distinguished between responders and non-responders to antidepressant treatment in the Holtzman strain. Finally, hypermetabolism of the lateral habenula and a less interactive prefrontal-limbic cortex were identified in subjects with higher susceptibility towards helplessness within the Holtzman strain. Similar findings have been reported with other depression animal models and human neuroimaging studies. These findings support that the helpless dimension of mood disorders can be accurately modeled with the Holtzman rat strain and confirm that the lateral habenula and prefrontal cortex are key regions mediating the helpless phenotype and response to SSRI treatment.text
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Gonçalves, Ana Margarida Matos. "Avaliação do Risco Ambiental de Antidepressivos." Master's thesis, 2018. http://hdl.handle.net/10316/87293.
Full textAbstract:
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA evolução da ciência ao longo dos séculos levou a grandes avanços na área de desenvolvimento de produtos farmacêuticos, melhorando em muito a vida humana, contudo, o consumo de produtos farmacêuticos tem vindo a aumentar gradualmente com o passar dos tempos e, consequentemente, contaminando o meio ambiente. A ocorrência desses compostos no meio ambiente tem levantado preocupações em todo o mundo devido ao seu impacto nos ecossistemas.Através de vários estudos, verificou-se que os medicamentos e os seus metabolitos exerciam sua ação sobre os organismos vivos pertencentes a esses ecossistemas, principalmente no ambiente aquático. Devido a esse perigo apresentado, a Agência Europeia de Medicamentos (EMA), em 2006, publicou a sua diretriz sobre Avaliação de Risco Ambiental (ERA) de medicamentos para uso humano, discriminando as normas e procedimentos necessários para prever o possível impacto que novas autorizações de introdução no mercado de medicamentos podem ter sobre o ambiente.Assim, o presente trabalho tem como principal objetivo realizar a ERA de cinco antidepressivos pertencentes a inibidores seletivos de recaptação de serotonina (ISRSs), através da revisão de dados da literatura científica relativos a ocorrência e toxicidade para organismos aquáticos não-alvo.Foi avaliado o risco ecotoxicológico dos ISRSs selecionados para diferentes níveis tróficos de organismos aquáticos, através de quocientes de risco (RQs) pela relação entre a Concentração Ambiental Medida (CAM) e a Concentração Prevista de Não-Efeito (PNEC). A Fluvoxamina, foi o único composto encontrado em águas residuais e superficiais, com RQ menor que 1 para todos os níveis tróficos, onde nenhum risco é esperado. No entanto, os restantes fármacos representam um impacto negativo para o meio ambiente aquático.
The evolution of science over the centuries has led to major advances in the development of pharmaceuticals, greatly improving human life, however, the consumption of pharmaceuticals has gradually increased and consequently contaminating the environment. The occurrence of these compounds in the environment has raised worldwide concerns due to their impact on ecosystems.Through several studies, it was verified that the drugs and their metabolites exerted their action on the living organisms belonging to these ecosystems, namely the aquatic environment. Due to this danger, the European Medicines Agency (EMA) published in 2006 its Guideline on Environmental Risk Assessment (ERA) for Medicinal Products for Human Use, setting out the rules and procedures necessary to predict the possible impact of new authorizations medicinal products may have on the environment.The main objective of the present study was to perform the ERA of five antidepressants belonging to selective serotonin reuptake inhibitors, through a review of the literature data on the occurrence and toxicity of non-target aquatic organisms.The ecotoxicological risk of SSRIs selected for different trophic levels of aquatic organisms was evaluated through risk quotients (RQs) by the relationship between the Measured Environmental Concentration (MEC) and the Predicted No Effect Concentration (PNEC). Fluvoxamine was the only compound found in surface and wastewater, with RQ<1 for all trophic levels; where, no risk is expected. However, the remaining drugs have a negative impact on the aquatic environment.