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1
Shiah, I.-Shin. "Neuroendocrine challenge studies of serotonin and GABA function in mania and in the mechanism of action of the mood stabilizer divalproex sodium." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0017/NQ46424.pdf.
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Kale, Andrea, and Yuliya Kuchanskaya. "Adherence to Mood Stabilizers Using a Pharmacy Prescription Database Analysis: Assessment of the Relationship of Non-Adherence to Hospitalization Rates, Cost of Care, and Gender for Patients with Bipolar Type I Disorder." The University of Arizona, 2006. http://hdl.handle.net/10150/624605.
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Class of 2009 AbstractObjectives: This study utilized a prescription claims database to retrospectively assess the relationship between adherence rates with a mood stabilizer in bipolar type I patients for: gender, age, psychiatric hospitalization rates, cost of services, and concomitant psychotropic medications. Methods: Adult patients with bipolar type I disorder (N=149; F=92 and M=57) who received at least two prescriptions of a mood stabilizer (i.e., carbamazepine, lamotrigine, lithium, oxcarbazepine, and valproic acid) during a 3-month intake period were included. Adherence to the mood stabilizer was retrospectively analyzed using high: >75% (> 274 days) vs. low: < 75% (< 274 days) supply of a mood stabilizer during 12-months. Results: Only 35.6% of the patients (N=53) met the criteria for > 75% adherence and 11.4% (N=17) met the criteria for > 90% adherence. There was a trend toward women having more days supply of a mood stabilizer compared to men (p=0.08) and older patients having a higher adherence rate with a mood stabilizer (p=0.06). The high adherence group had greater prescription costs (p<0.001) and total cost per year (R2=0.34, p=0.064) and more concomitant medications (p=0.04) than the low adherence group. Overall, there were no significant differences between the high and low adherence groups for mean hospital days, inpatient costs, and total cost of care. Among those patients that were hospitalized there was a negative correlation between adherence and inpatient cost (R2=0.49, p=0.024). Conclusions: Our findings suggest that patients with bipolar type I disorder demonstrate poor medication adherence with a mood stabilizer and that adherence rates based on a prescription claims database using two adherence categories may not be a predictive factor for psychiatric hospitalizations or cost of care.
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Schulze, Thomas G., Martin Alda, Mazda Adli, Nirmala Akula, Raffaella Ardau, Elise T. Bui, Caterina Chillotti, et al. "The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134635.
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For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its effortsDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Pilhatsch, Maximilian, Tasha Glenn, Natalie Rasgon, Martin Alda, Kemal Sagduyu, Paul Grof, Rodrigo Munoz, et al. "Regularity of self‑reported daily dosage of mood stabilizers and antipsychotics in patients with bipolar disorder." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-235821.
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Background
Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics.
Methods
Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity.
Results
There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049).
Conclusion
Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.
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Schulze, Thomas G., Martin Alda, Mazda Adli, Nirmala Akula, Raffaella Ardau, Elise T. Bui, Caterina Chillotti, et al. "The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment." Karger, 2010. https://tud.qucosa.de/id/qucosa%3A27583.
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For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Jing, Yonghua. "Health Outcomes Assessment for Children and Adolescents with Bipolar Disorder Treated with and without Atypical Antipsychotics." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1235785106.
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Takahashi, Tatsuichiro. "Factors associated with high-dose antipsychotic prescriptions in outpatients with schizophrenia: An analysis of claims data from a Japanese prefecture." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/265180.
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京都大学新制・課程博士
博士(医学)
甲第23408号
医博第4753号
新制||医||1052(附属図書館)
京都大学大学院医学研究科医学専攻
(主査)教授 中山 健夫, 教授 古川 壽亮, 教授 村井 俊哉
学位規則第4条第1項該当
Doctor of Medical Science
Kyoto University
DFAM
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Bartsch, Stefanie. "Auswirkung von Stimmungsstabilisierern und Antiepileptika auf die Zytokinproduktion in-vitro." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-156211.
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Die Bedeutung des Immunsystems in der Pathophysiologie von bipolaren Erkrankungen und Epilepsie ist ein aktueller Gegenstand der neuropsychoimmunologischen Forschung. Eine erhöhte Produktion von Zytokinen aufgrund von oxidativem Stress wurde dabei wiederholt als für die Pathophysiologie von Epilepsie und Bipolarer Störung relevant angesehen. In Hinblick auf Veränderungen der Zytokine Interleukin (IL)-1ß, IL-2, IL-4, IL-6 und Tumornekrosefaktor-alpha (TNF-α) wurden z. T. überlappende Ergebnisse bei beiden Erkrankungen beschrieben. Inwiefern diese Zytokine durch Stimmungsstabilisierer und Antiepileptika beeinflusst werden, wurde bisher jedoch nicht systematisch untersucht.
In dieser Studie wurden systematisch in-vitro die Konzentrationen von IL-1ß, IL-2, IL-4, IL-6, IL-17, IL-22 und TNF-α im stimulierten Blut 14 gesunder Frauen mittels Vollblutverfahren (whole blood assay) nach Zugabe von Stimmungsstabilisierern bzw. Antiepileptika gemessen. Es wurden dabei die Stimmungsstabilisierer bzw. Antiepileptika Primidon, Carbamazepin, Levetiracetam, Lamotrigin, Valproat, Oxcarbazepin, Topiramat, Phenobarbital und Lithium untersucht.
Die Ergebnisse lassen darauf schließen, dass der Mechanismus von erwünschter und unerwünschter anderer Wirkung von Stimmungsstabilisierern und Antiepileptika mit der Regulation von IL-1ß, IL-2, IL-22 und TNF-α in Zusammenhang stehen könnte.
Getrennt nach den im Vollblutverfahren verwendeten Stimulanzien – Toxic-Shock-Syndrome-Toxin-1 (TSST-1) vs. monoklonaler Antikörper gegen das CD3-Oberflächenantigen (OKT3) in Kombination mit dem 5C3-Antikörper gegen CD40 (OKT3/CD40) – wurden die Ergebnisse in zwei unterschiedlichen Publikationen berichtet, die dieser Promotion zugrunde liegen.
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Shansis, Flavio Milman. "Escalas de avaliação do estado maníaco e de depressão : concordância na resposta a medicações estabilizadoras do humor em pacientes bipolares com sintomatologia mista." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/127226.
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Introdução: Comparados com pacientes bipolares com episódios maníacos/hipomaníacos e depressivos, os que apresentam estados mistos tendem a curso mais grave da doença, início mais precoce, ocorrência mais frequente de sintomas psicóticos, maior risco de suicídio, altas taxas de comorbidade e tempo maior para remissão. Portanto, medidas objetivas de avaliação desses estados são necessárias. Objetivo:Avaliar a concordância entre três pares formados por uma de três escalas de mania (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) ou Clinician-Administered Rating Scale for Mania (CARS-M)) e uma de depressão (21-item Hamilton Depression) na avaliação da resposta a estabilizadores do humor em pacientes mistos. Método:Sessenta e oito (n=68) consecutivos pacientes ambulatoriais bipolares Tipo I e II com sintomatologia mista pelo DSM-IV-TR e pelos critérios de Cincinatti foram incluídos nesse estudo aberto de 8 semanas entre 2010 e 2014 foram randomizados para receberem em monoterapia, ácido valproico, carbamazepina ou carbonato de lítio. Resultados: O padrão de resposta (diminuição de, pelo menos, 50% em uma das escalas de mania e na de depressão) foi muito semelhante: 21-HAM-D + YMRS = 22,1%, 21-HAM-D + BRMS = 20,6% e 21-HAM-D + CARS-M = 23,5%; p < 0,368). Os resultados referentes à concordância de resposta revelam valores de kappa bastante altos: 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0,87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0,78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0,91 (p < 0,001). Conclusões:O presente estudo sugere que qualquer uma das três escalas de mania utilizadas (YMRS, BRMS, CARS-M) pode ser associada à 21-HAM-D na avaliação da resposta em bipolares mistos.Background: Compared with patients with bipolar disorder who exhibit pure manic/hypomanic or depressive episodes, the presence of mixed mood states is associated with a more severe course of illness, younger age of onset, more frequent ocurrence of psychotic symptoms, major risk of suicide, higher rates of comorbidities and longer time to achieve remission. Therefore, objective avaliation of these states are necessary. Objective: To evaluate the concorccance amog three pairs of three scales (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) or Clinician-Administered Rating Scale for Mania (CARS-M)) and a depression scale (21-item Hamilton Depression) in the assessment of response to humor stabizator drugs in mix bipolar patients. Methods: Sixty eight (n=68) consecutive bipolar type I and II outpatients with mixed sitomatology accordint to DSM-IV-TR and Cincinatti Criteria were included in these 8 weeks open-trial, from 2010 through 2014, to, randomly, receive monotherapy valporic acid, carbamazepine or lithium carbonate. Results: The response answer (decrease of, at least 50 %, in one of the mania and depression scales) were very similar: 21-HAM-D + YMRS = 22.1%, 21-HAM-D + BRMS = 20.6% e 21-HAM-D + CARS-M = 23.5%; p < 0,368). The kappa values were : 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0.87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0.78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0.91 (p < 0,001). Conclusions: The present study suggests that any of the three mania scales used (YMRS, BRMS, CARS-M) may be associated to 21-HAM-D in the assessment of the response o bipolar patients.
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Piva, Roger Honorato. "Zircônia CO-dopada por compensação de cargas nos sistemas (ZrO2)1-(x+y)(InO1,5)x(MOz)y com MOz = TaO2,5, NbO2,5, MoO3 ou WO3, como revestimento para barreira térmica." Universidade Federal de São Carlos, 2016. https://repositorio.ufscar.br/handle/ufscar/8318.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
InO1.5-stabilized zirconia (InSZ) is a potential hot corrosion resistant thermal barrier coating (TBC). However, the thermal instability prevents real applications of InSZ-based TBC. This thesis investigates the hypothesis of co-doping using the charge compensation to improve the phase stability of InSZ. Four co-doping systems were synthesized by coprecipitation and studied: (ZrO2)1-(x+y)(InO1.5)x(MOz)y with MOz = TaO2.5, NbO2.5, MoO3, or WO3. After synthesis, 9 mol% of InO1.5 plus the charge-compensating oxides was sufficient to stabilize the tetragonal phase. Specific surface area up to 106.1 m2.g-1 and crystallite size ~11 nm were achieved using ethanol washing followed by azeotropic distillation as dehydration technique in the precipitates. In these powders, initial thermal stability analysis indicated instability of the tetragonal phase, with extension of the t→m transformation less detrimental in the InMoSZ system. Further increase in the concentration of InO1.5:MoO3 results in monophasic samples with retention of cubic phase in the InMoSZ. Cubic InMoSZ exhibited hardness and thermal expansion coefficient of 13.5% and 9% higher than those of InSZ, respectively. However, thermal treatments at T ≥ 1200 °C showed that the InMoSZ is also passive to destabilization of the high temperature cubic polymorph. Although the cubic InMoSZ was the most promising system found in this thesis, the stability results do not support its application as TBC for temperatures ≥ 1000 ºC. A deep evaluation of the phase transformations between 1000 to 1200 °C indicated that the instability of the proposed systems is due to a progressive c→t→m destabilization of the polymorphs. This c→t→m transformation is directly associated with the reduction of the InO1.5 stabilizer in solid solution by volatilization as In2O during heat treatment. At temperatures ≤ 800 ºC, the c→t phase transformation do not occurs, then, InSZ-based TBC is stable in these conditions.
A zircônia estabilizada com InO1,5 (InSZ) é um material com potencial aplicação como revestimentos para barreira térmica (TBC) resistentes à corrosão. Contudo, a instabilidade de fases impede aplicações industriais da InSZ. Esta tese investiga a ação da co-dopagem por compensação de cargas como uma estratégia para aumentar a estabilidade de fases da InSZ. Quatro sistemas de co-dopagem foram sintetizados por co-precipitação e estudados: (ZrO2)1-(x+y)(InO1,5)x(MOz)y com MOz = TaO2,5, NbO2,5, MoO3 ou WO3. Após a síntese, 9 %mol de InO1,5 somado a concentração de óxidos compensadores de carga foi suficiente para estabilização da fase tetragonal. Área superficial específica de até 106,1 m2.g‒1 e tamanho de cristalitos de ~11 nm foram obtidos utilizando a lavagem com etanol seguida por destilação azeotrópica como técnica de desidratação dos precipitados. Para estes pós, testes de estabilidade térmica indicaram instabilidade da fase tetragonal, com extensão de transformação t→m menos detrimental no sistema InMoSZ. Aumentando gradativamente a concentração de InO1,5-MoO3 na InMoSZ resulta em amostras monofásicas com retenção da fase cúbica. A InMoSZ cúbica exibiu dureza e coeficiente de expansão térmica até 13,5% e 9% superiores aos valores da InSZ, respectivamente. No entanto, tratamentos em temperaturas ≥ 1200 ºC indicaram que a InMoSZ é também suscetível a desestabilização da fase cúbica. Embora a InMoSZ cúbica tenha sido o sistema mais promissor obtido nesta tese, os resultados de estabilidade indicam que sua aplicação como TBC não é possível em temperaturas ≥ 1000 ºC. Uma avaliação detalhada das fases formadas após os tratamentos entre 1000 a 1200 ºC demonstrou que a instabilidade dos sistemas estudados é decorrente de uma transformação progressiva tipo c→t→m. A origem da transformação c→t→m é associada a redução da concentração do estabilizador InO1,5 em solução sólida por volatilização como In2O durante os testes de estabilidade térmica. Em temperaturas ≤ 800 ºC, a transformação c→m não ocorre, neste caso, TBCs baseadas em InSZ são estáveis termicamente para aplicações industriais.
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Penteado, Ana Julia. "Estudo do efeito da n-acetilcisteína sobre a toxicidade induzida pelo lítio." Universidade Estadual do Oeste do Paraná, 2017. http://tede.unioeste.br/handle/tede/2958.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Lithium carbonate is the main drug used to treat bipolar disorder. This medicine has a narrow therapeutic range and is usually used in a chronic way by the patients, generating the need for therapeutic monitoring by means of plasma lithium quantification. In addition, records of toxic effects from chronic medical use reinforce the need for a tool that assists in the treatment. Thus, a reliable methodology for the quantification of lithium and a therapeutic adjuvant emerge as a means to improve the quality of life of the patient. In our work, we used the flame atomic absorption spectrometer to validate the method for quantification of lithium and the results were satisfactory, because they complied with the required criteria, assuring the reliability of the method. In order to find a therapeutic adjuvant, N-acetylcysteine (NAC) was studied for presenting important characteristics against the toxic effects caused by lithium. In our results lithium presented toxic effects mainly inducing oxidative stress, while the coadministration of NAC reversed this effect in the liver, kidney and brain organs. The use of NAC as a therapeutic adjuvant has been shown to be promising, however, further studies need to be performed to better understand this relationship.
O carbonato de lítio é o principal medicamento utilizado no tratamento do transtorno bipolar. Este medicamento possuí estreita faixa terapêutica e geralmente é utilizado de forma crônica pelos pacientes, gerando a necessidade da monitorização terapêutica por meio da quantificação plasmática de lítio. Além disso, os registros de efeitos tóxicos decorrentes do uso medicinal crônico remetem a necessidade de uma ferramenta que auxilie no tratamento. Desta forma, uma metodologia confiável para a quantificação de lítio e um adjuvante terapêutico surgem como meios de melhorar a qualidade de vida do paciente. Em nosso trabalho, utilizamos o espectrômetro de absorção atômica de chama para validar um método para quantificação de lítio e os resultados foram satisfatórios, pois cumpriram os critérios exigidos, assegurando a confiabilidade do método. Com foco em buscar um adjuvante terapêutico, a N-acetilcisteína (NAC) foi estudada por apresentar características importantes contra os efeitos tóxicos causados pelo lítio. Em nossos resultados o lítio apresentou efeitos tóxicos principalmente induzindo o estresse oxidativo, enquanto que a coadministração de NAC reverteu esse efeito nos órgãos fígado, rim e cérebro. O uso da NAC como adjuvante terapêutico mostrou ser promissor, porém, mais estudos precisam ser realizados para entender melhor essa relação.
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Chen, Po-see, and 陳柏熹. "Neuroprotective effects of the mood stabilizer valproate: role of glia." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/25276977109558104988.
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博士國立成功大學
基礎醫學研究所
96
The brain is the most intricate organ in the human body. The brain maintains internal homeostasis and adapt to the changing environment. Neurons are believed to underlie the function of the brain. Glial cells, including astrocytes, oligodendrocytes, and microglia, are estimated to outnumber neurons by about ten to one. Although glial cells constitute over 50% of brain cells, their involvement in normal brain function is poorly understood. An emerging alternative view holds that neuroglia coordinate brain function. Nowadays, astrocytes are known to provide nutrients, oxygen and maintain the homeostasis of the blood-brain barrier. Astrocytes have also been reported to play an active role in information transmission through the regulation of extrasynaptic neurotransmitter concentration. Oligodendrocytes make up the myelin sheath. Microglia can destroy foreign pathogens and remove dead neurons. In addition, glial cells can guide the migration of neurons in the early developmental stage of the brain and secrete factors to regulate the formation of neuritis. They also play a critical role in synaptogenesis and synaptic plasticity. Researchers also discovered that glial cells play important roles in the pathogenesis of neuropathic pain, epilepsy, neurodegenerative disorders, schizophrenia and affective disorders. Glial cells are now considered as important targets for pharmacological treatments of brain disorders. Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes unusual shifts in a person's mood, energy, and ability to function. Previous structure and functional images for bipolar disorder showed the cell loss and brain atrophy in human suggested the consequence of cellular pathology. Nowadays there are structurally highly dissimilar mood stabilizers used to effectively treat and prevent the occurrence of bipolar disorder. Till now, there has been no consensus on direct neuronal mechanisms underlying the therapeutic actions. However, previous in vitro and clinical studies indicated they share the commonalities of neuroprotective and neurotrophic effects. Because the effects of mood stabilizers on glial cells have seldom been investigated plus that valproate, a vii mood stabilizer, is known to regulate the cellular epigenetic status through histone modifications, a series studies were performed to investigate the direct effect of valproate on glial cellular function and epigenetic status, and the indirect effects on neuroprotection using primary mixed neuron-glial culture systems. The results showed that valproate can protect midbrain dopaminergic neurons from inflammatory injury by inhibiting the production of microglial inflammatory factors and inducing microglial apoptosis. More importantly, valproate could increase the astroglial production of neurotrophic factors. In turn, the increase in neurotrophic factors has trophic effects on midbrain dopaminergic neurons. All of these effects are mediated through the increase in specific glial histone protein acetylation that changes genes expression. The results suggest that glial cells play important roles in the neuroprotective effects of valproate. Besides, valproate could modulate the function of midbrain dopaminergic neurons through its direct effects on glial cells. These results suggested glial cells could be the important cellular therapeutic targets for valproate which may act as an epigenetic regulator. In the future, a series of studies would be proceeded to examine the role of glial cells and epigenetic phenomenon in the pathogenesis and treatment of bipolar disorder. Insights from these studies may advance our understanding of the pathogenesis of complex psychiatric diseases and also the development of epigenetic therapy.
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Chen, Yu-Han, and 陳鈺涵. "Anti-inflammatory effects of the mood stabilizer-lamotrigine on LPS-activated macrophage." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/pgf8b2.
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碩士臺北醫學大學
醫學科學研究所
102
Bipolar disorder (BD) is a chronic psychosis, characterized by persistent mood changes involving both elevated and depressed mood states. According to previous researches, patients with BD have been reported to have altered immune functions. Lamotrigine (LTG), a phenyltriazine derivative and anti-epileptic drug, has emerged as an effective firstline treatment for bipolar mood disorder. Like the other mood stabilizers lithium and valproate, LTG also has neuroprotective properties but its exact mechanisms remain poorly defined. LTG is well-characterized as a voltage-gated sodium (Na+) channel inhibitor and subsequently stabilizes neuronal membranes and suppresses post-synaptic release of excitatory amino acids, notably glutamate. The aim of this study is designed to investigate the effects and mechanisms of lamotrigine on the function of macrophage and cell viability and on regulation the mouse Type II collagen-induced arthritis (CIA) model. In the past study, the level of interleukin-6 (IL-6) and TNF-α are increased by lipopolysaccharide (LPS)-induced macrophage activation. The report shows the level of IL-6 and TNF-α decreased by lamotrigine. These data suggest that lamotrigine could modulate macrophage functions, and might have potential role in immunomodulation. The binding of Interleukin 6—family cytokines to the gp130 receptor triggers STAT3 phosphorylation by JAK2. Furthermore, we want to investigate the level of IL-6 and TNF-α decreased by lamotrigine and reduces the expression of phosphorylation STAT3. Lamotrigine inhibits of lipopolysaccharide (LPS)-induced macrophage activation and may provide beneficial effects in anti-inflammatory. Furthermore, we want to investigate the immunomodulation effect of lamotrigine on the mouse Type II collagen-induced arthritis (CIA) model. Our results show oral treatment with LTG in CIA mice decreased paw thickness and inflammatory scores. These data suggest that treatment with LTG has effects on LPS-induced macrophage activation and on CIA model.
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Ferreira, Ana Sara Rocha Ramos. "Internship and Monograph reports entitled"Lithium as a Mood Stabilizer in Bipolar Disorder"." Master's thesis, 2020. http://hdl.handle.net/10316/92986.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaAs doenças mentais afetam cerca de 450 milhões de pessoas em todo o mundo. De acordo com a World Health Organization, este conceito inclui diversas condições, tais como demência, depressão, esquizofrenia, transtornos de desenvolvimento e perturbação bipolar. A perturbação bipolar está entre as dez doenças consideradas mais debilitantes a nível mundial e afeta mais de 1 % da população. O aumento da mortalidade aliado à elevada taxa de suicídio na perturbação bipolar suporta a necessidade emergente de desenvolver novas abordagens farmacológicas e não-farmacológicas e novos alvos terapêuticos para o tratamento desta patologia.Apesar da estreita margem terapêutica do lítio, a sua utilização como estabilizador de humor é cada vez mais frequente devido às evidências clínicas que demonstram a sua eficácia no tratamento de manutenção em indivíduos com perturbação bipolar, o seu efeito preventivo em perturbações afetivas e a sua função ímpar na prevenção do suicídio. Atualmente, os mecanismos de ação que conferem ao lítio a sua capacidade enquanto estabilizador de humor permanecem incertos; contudo, múltiplos estudos sugerem a inibição da glicogénio sintase quinase 3 e a inibição da enzima inositol monofosfato.Neste sentido, o presente trabalho tem como objetivo fazer uma revisão bibliográfica das atuais opções farmacológicas prescritas e algumas das diferentes linhas terapêuticas em contextos de mania aguda, depressão bipolar e tratamento de manutenção da perturbação bipolar. Os mecanismos de ação que permitem que o lítio seja utilizado como primeira linha terapêutica em inúmeros doentes irão ser especificados, paralelamente com as caraterísticas farmacológicas e farmacocinéticas do lítio, a sua terapêutica, efeitos adversos, limitações clínicas e indicações terapêuticas.
Psychiatric conditions affect around 450 million people worldwide. According to the World Health Organization (WHO), “mental disorders” concept includes several conditions such as dementia, depression, schizophrenia, development disorders and bipolar disorder (BD). BD is among the ten most disabling conditions in the world and affects more than 1 % of the population. The increased mortality and the suicide rate in BD reflect the emergent need of improving the existent pharmacological and non-pharmacological approaches and to identify new therapeutic targets.Despite its narrow therapeutic range, lithium carbonate is frequently used as a mood stabilizer based on the substantial clinical evidence regarding its efficacy as maintenance treatment of BD, preventive effect in mood disorders and its unique role in suicide prevention. Currently the exact mechanisms of action underlying the therapeutic effect of lithium as mood stabilizer remain unclear; however, multiple studies suggested the inhibition of glycogen synthase kinase 3 (GSK-3) and the inhibition of inositol monophosphatase enzyme (IMPase).In this context, the present work reviews the current pharmacological options and some different lines of therapy in acute mania, bipolar depression and long-term treatment of BD. Specifically, the mechanisms of action of lithium that are making it the first-line treatment of BD will be herein focused in parallel with lithium’s pharmacological and pharmacokinetic characteristics, therapeutic and adverse effects, clinical limitations and medical applications.
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Pasiliao, Clarissa. "The Role of Glutathione Metabolism in the Neuroprotective Effect of Mood Stabilizers." Thesis, 2010. http://hdl.handle.net/1807/25888.
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Several lines of evidence implicate oxidative stress in the pathophysiology of bipolar disorder (BPD). The mood stabilizers lithium and valproate have been shown to protect against oxidative stress-induced cell death. This study examined whether an increase in cellular reductive potential due to glutathione (GSH) synthesis up-regulation underlies this neuroprotective effect. Using primary rat cortical neurons as a model, this study demonstrated that unlike lithium and valproate, carbamazepine and lamotrigine do not exert neuroprotective effects against H2O2-induced cell death. Moreover, the level of GSH and the GSH:GSSG ratio in neurons and in rat brain remained unchanged following chronic treatment with either lithium or valproate. Similarly, this study did not find a significant effect of treatment on the expression of genes encoding γ-glutamylcysteine ligase sub-units, Gclc and Gclm, in both neurons and the rat brain. These findings suggest that other molecular targets of lithium and valproate likely mediate the observed neuroprotective effects.
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Kwan, Melodie. "Effect of the mood stabilizer valproate on intracellular calcium homeostatis in bipolar I disorder." 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=95225&T=F.
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Heinrich, Annette. "Molecular mechanisms of the effect of the mood stabilizer lithium on cAMP-induced CREB transcriptional activity." Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-B4F9-9.
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Masuch, Annette [Verfasser]. "Molecular mechanisms of the effect of the mood stabilizer lithium on cAMP-induced CREB transcriptional activity / submitted by Annette Heinrich." 2009. http://d-nb.info/997336862/34.
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Nuss, Margarita. "Pharmakologische Behandlung von stationären Patienten mit einer emotional instabilen Persönlichkeitsstörung." Doctoral thesis, 2016. http://hdl.handle.net/11858/00-1735-0000-0028-86F3-9.
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Chirulescu, Cecilia. "Combination antipsychotic and mood stabilizers in maintenance treatment of bipolar patients in community practice." Thesis, 2009. http://hdl.handle.net/10539/6010.
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Abstract
Bipolar disorder is a complex illness. It is a life long episodic disorder very
disruptive for the patient and family. Repeated episodes lead to progressively
deteriorating level of functioning and poor response to the treatment. Suicide attempts and
completed suicide has been a frequent complication.
The complexity and difficulties involved in treating this mental condition are well
recognised .The pharmacological options include lithium, valproate, carbamazepine,
lamotrigine, topiramate, benzodiazepines.
The use of neuroleptics in bipolar disorder remain controversial because of the
increased susceptibility of this group of patients to side effects of neuroleptics.
Objectives:
The aim of this research is to investigate in a population of patients with bipolar disorder who
are having treatment with combination of a mood stabilizer and antipsychotics:
1) The number of prescriptions of antipsychotics, in bipolar patients in a community clinic
2) The rationale of such combination
3) Whether correlates exist between variables such as substance abuse and noncompliance
and the prescription of antipsychotics
Method:
This retrospective, descriptive, analytic study was conducted at Voslooros Psychiatric
Clinic, which is situated in the south of Johannesburg. The clinical records of all adult
patients with an initial diagnosis of bipolar disorder as at December 2004 were examined
Particular note was taken of demographic data, diagnosis, age of onset of psychiatric illness,
V
duration of illness, treatment prescribed, reasons for prescribing this medication, response to
the treatment, social circumstances of each patient, substances use and compliance.
Results:
74.1% of the patients were maintained on a combination of mood stabilizer with antipsychotic.
Combination treatment was used in an attempt to improve the psychotic symptoms and
dangerous behaviour in 48% of the patients, noncompliance in 38% of the cases and 14%
patients were in transitional phase to stop antipsychotics.
80.65% of the patients were on treatment with antipsychotics for longer than 6 months.
Use of atypical antipsychotics is associated with a better outcome than the conventional
agents. In this study only a small percentage (10 %) of patients received atypical
antipsychotics.
19.4 % patients reported side effects of the medication. The lower figures in our study can
be due to underreporting and inadequate documentation.
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38.7% of the patients reported substance misuse. Our finding were much lower compared
with the literature, probably due to underreporting. Alcohol was the most common substance.
This study show that the need for more medication was increased 6.6 fold in patients with
polysubstance abuse compared with the patients not abusing any substance.
Noncompliance in the maintenance phase of the treatment is a important issue in the
management of the patients with bipolar disorder. This study found that the majority of the
patients (59.7%) were noncompliant with their treatment.
Those findings were in line with studies done by Keck PE who reported rates of
noncompliance from 51% to 64%. Our study show that 63% of the patients had a level of
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education less than matric and this may be a contributing factor to noncompliance.
Conclusions:
The results of the study suggest that a large number of bipolar patients are only
partially responsive to mood stabilizers alone and the maintenance treatment with
antipsychotics for longer than 6 months are needed because of persistence of the symptoms.
More efficient strategies are necessary to educate the people, to improve the compliance
and to decreased the use of substances.
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Bakare, Adedolapo Olawunmi. "Effect of mood stabilizers in the regulation of glutathione-s-transferase M1 expression." 2007. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=788773&T=F.
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Chau, Pei-Fang, and 趙培芳. "Studies of Utilization of Mood Stabilizers and Related Adverse Drug Reactions in Bipolar Patients." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/33978189029410521630.
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碩士國立臺灣大學
臨床藥學研究所
94
Background The mood stabilizers for bipolar disorder include lithium, valproate and carbamazepine. According to previous studies, lithium and carbamazepine were considered to be associated with the development of hypothyroidism and SJS/TEN, respectively. The pharmacoepidemiology data for bipolar patients is important for clinical practice and medical policy. Objective To analyze the prescription pattern of bipolar disorders from 1997 to 2004. To evaluate the adverse drug reactions, i.e. hypothyroidism and SJS/TEN, of mood stabilizers in bipolar patients. Methods The Psychiatric Inpatient Medical Claim dataset (PIMC) in Taiwan was used in this study. Medical claim data between 1997 to 2004 of the bipolar patients diagnosed during 1996-2001 were retrieved. The utilization patterns of mood stabilizers, antipsychotics, antidepressants and electroconvulsive therapy were calculated and analyzed. The matched case-control design with one case to four controls was used for the ADR studies. Bipolar patients who fit the inclusion criteria of case group were screened first. The control group of the same age range and sex to the cases was retrieved from patients other than the case group. Conditional logistic regression model using to calculate the adjusted odds ratio was applied to analyze the relationship between hypothyrodism or severe skin reactions and the drugs used by the bipolar patients. Results A total of 12,424 patients of bipolar disorder who had a mean age of 40.2 year old and equal gender ratio were included. From 1997-2004, the use of atypical antipsychotics (β=0.42, p<0.0001) increased significantly with a decrease in typical antipsychotics (β= - 0.23, p<0.0001). For mood stabilizers, the prescriptions of valproate (β=0.25, p<0.0001) increased significantly along with the significant decreases of lithium (β=-0.091, p<0.0001) and carbamazepine (β=-0.096, p<0.0001). A total of 557 bipolar patients with hypothyroidism were identified and 2,228 controls were selected. The mean age of these patients was 41.3 year old with a ratio of man to women 1:3. After adjustment, lithium did not exhibit higher risk in hypothyroidism as compared to carbamazepine and valproate. Patients who have ever used both lithium and valproate or who have ever used all the three mood stabilizers have significant risk of developing hypothyroidism. If considered the number of mood stabilizers used as a continuous factor, it was found that the more mood stabilizers used the higher risk in developing hypothyroidism (OR 1.34, 95% CI 1.21-1.49). There were 74 cases with severe skin reactions and two of them did not have any prescription within the 60 days before the index date. Finally, 72 cases and 288 controls were identified from the 12,424 bipolar patients. The number of man and women were about the same with a mean age of 41.3 years old. After multivariate analysis, carbamazepine and valproate were found significantly associated with severe skin reactions. The other anticonvulsants also had significant association as calculated as a group of drugs. Among the suspicious drugs, carbamazepine showed the highest risk in developing the severe skin reactions (OR 4.02, 95% CI 1.97-8.27). Conclusions The prescription pattern of bipolar disorder during 1997 to 2004 has a significant change and this change seems to be consistent with recent guidelines. Using more than two mood stabilizers may lead to a higher risk of hypothyroidism. Closely monitor thyroid function for these patients may be necessary. Carbamazepine has the highest risk of causing severe skin reactions among all suspicious drugs in bipolar patients. The association of other anticonvulsants also could not be ignored. It is important to be aware of shin reactions during anticonvulsants treatment.
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Grave, Ana Sofia Leite. "Long-term adverse effects of chronic use of psychotropics: the case of antidepressants, anxiolytics and mood-stabilizers." Dissertação, 2020. https://hdl.handle.net/10216/128239.
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Grave, Ana Sofia Leite. "Long-term adverse effects of chronic use of psychotropics: the case of antidepressants, anxiolytics and mood-stabilizers." Master's thesis, 2020. https://hdl.handle.net/10216/128239.
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Chang, Chi-wei, and 張琦偉. "The Association Between Leptin Receptor Gene Polymorphisms and Mood Stabilizers Induced Metabolism Abnormalities in Patients with Bipolar Disorder." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/03388175473825753142.
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碩士國立成功大學
藥理學研究所
96
Valproic acid and lithium are mood stabilizers that were used for bipolar patients. The major side effect of valprioc acid and lithium is medication induced metabolic abnormalities. However, the effect is variable between individuals. In our study, we try to test whether single nucleotide polymorphisms (SNPs) of the leptin receptor (LEPR) gene that corresponding to feeding behavior and energy expenditure are associated with the metabolic abnormalities caused by mood stabilizers. Subjects (n=117) meet the DSM-IV criteria for bipolar disorder were recruited from the National Cheng Kung University Hospital. Metabolic indexes were measured. Specific SNPs of the LEPR chosen from Hapmap project were genotyped. The linkage disequilibrium and haplotypes of the SNPs were first estimated by the Haploview program. Then we tested the possible associations between genetic variances and metabolic indexes analyzed by SPSS program. Results showed the genotype frequencies of the rs1327121, rs8179183 and rs4655555 variances were significantly different between patients and control. Besides, the frequency of haplotype AGT composed of rs1327121, rs8179183 and rs4655555 were significantly higher in control than in the patient group. It suggested that people who own haplotype AGT might be protected from bipolar disorder. Variances of the rs12145690, rs9436747 and rs8179183 were associated with metabolic indexes in patients, these variances might relate to the metabolic changes of bipolar patients taking mood stabilizers. The correlation between metabolic indexes and plasma valproate levels were significantly different among different rs1327121 and rs9436747 genotypes. These results indicated that valproate might induce different metabolic responses in different LEPR genotypes. Our study indicated SNPs of LEPR gene were associated with bipolar disorder and metabolic changes induced by mood stabilizers.
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Perova, Tatiana. "Differential modulation of intracellular calcium responses in B lymphoblasts by mood stabilizers: Relevance to the molecular therapeutics of bipolar disorder." 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=450624&T=F.
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Hroudová, Jana. "Vliv antidepresiv a depresivní poruchy na mitochondriální funkce." Doctoral thesis, 2012. http://www.nusl.cz/ntk/nusl-305986.
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Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...
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Cikánková, Tereza. "Vliv psychotropních látek na mitochondriální funkce." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-437212.
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Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...