Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 170-191). Available also in a digital version from Dissertation Abstracts.

Thesis (doctoral)--University of Uppsala, 1984. / Bibliography: p. 33-45.

Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medications. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic variants associated with obesity risk; however the effects of these risk variants on clozapine-induced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling event by which clozapine could induce a change in mRNA expression of the obesity-related genes? The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression of most obesity-related genes tested was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway. In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesity-related genes.

Yes / Background: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects. Aims: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit. Methods: We used data from two dose–response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations. Results: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation. Conclusions: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal.

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. . 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 VI 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.

SAMMANFATTNING Bakgrund: Antipsykotika utgör grunden i behandling av psykossjukdomar. Bristande följsamhet till läkemedelsbehandlingen är dock vanligt förekommande och en stor anledning till att patienter återinsjuknar i psykos och behöver vårdas inom slutenvård. Syfte: Dels att beskriva hur patienter som vårdas inom sluten psykiatrisk psykosvård uppfattar läkemedelsadministrering och dels att beskriva om patienterna uppfattar att sjuksköterskors bemötande i samband med läkemedelsadministrering har betydelse för deras inställning till att medicinera. Metod: Kvalitativ ansats. Intervjustudie med fenomenografi som metod i datainsamling och analys. Resultat: Tio beskrivningskategorier identifierades: Läkemedel befogat och bra, tar läkemedel trots ambivalens/motstånd, läkemedelsadministrationen – ett odramatiskt moment, tvångsmedicinering, behov av information om läkemedel, att vilja ha kontroll eller överlåta ansvar, en stressig situation, belöning för medverkan i medicinering, bemötandet spelar ingen roll och bemötandet spelar stor/viss roll.  Slutsats: Patienter som vårdas inom sluten psykiatrisk psykosvård uppfattar medicinering med antipsykotika och momentet läkemedelsadministration olika. Dessa individuella uppfattningar skulle troligtvis kunna identifieras om rutiner för samtal med patienter kring dessa frågor utarbetas på avdelningar där sådan vård bedrivs. Sannolikheten för att frivilliga lösningar och en bättre individuellt anpassad vård lättare skulle kunna bedrivas borde då öka. Strävan måste vara att så långt det är möjligt undvika tvångsmedicinering och situationer och bemötande som i denna studie identifierats som mindre positiva då de kan utgöra en risk att patienter blir negativt inställda till att medicinera. Ambitionen måste vara att hitta arbetssätt som syftar till långvarig följsamhet. / ABSTRACT Background: Antipsychotics are the basis of the treatment of psychotic illnesses. Lack of adherence to medication is common and a major reason why patients recurrence of psychosis and need to be cared for in hospital. Purpose: To describe how patients with psychosis, cared for in inpatient psychiatric wards, understand medication administration and also to describe if the patients perceive that nurses treatment in the moment of medication administration has an impact on their attitudes to medicate. Method: Qualitative approach. An interview study with phenomenography as a method of data collection and analysis.  Results: Ten categories were identified: medicines justified and well, take medicine despite ambivalence/resistance, administration of medicine – an undramatic moment, coerced medication, need for information about medicines, want to have control or assign responsibility, a stressful situation, reward for participation in the medication, treatment don´t  matter and treatment play a major/some role. Conclusion: Patients with psychosis, who are cared for in inpatient psychiatric wards, understand medication with antipsychotics and the moment of drug administration different. These individual understandings would likely be identified if routines for dialogue with patients about these issues were developed at wards where such care is conducted. The probability of voluntary solutions and better individualized care should then be increased. The ambition must as far as possible be to avoid forced medication and situations identified as less positive in this study as they may pose a risk to cause negative attitudes to medication among patients.  The ambition must be to find ways of working aimed at long-term adherence.

The purpose of present thesis work was to investigate the pharmacokinetics of FLU and four aliphatic esters, FLU-A, FLU-B, FLU-E and FLU-D, and in particular, the impact of the ester groups on the pharmacokinetics of the parent compound FLU after administration of the prodrugs in oil based injections. It was determined that the sesame oil/buffer partition coefficients (PC) decreased as the homogenous series of the ester chain length was increased, the effect of the chain length of the prodrug on the release rate of the corresponding prodrug from the oily depot. Furthermore, the results from 'in vitro ' enzymatic experiments using plasma, liver and muscle homogenates obtained from dog or human showed that lipophilicity of the esters predominated over other parameters such as enzymatic hydrolysis in determining the sustained production of FLU when the prodrugs were given as oil based intramuscular depot formulations. The roles of depot injection sites and proximal lymph nodes in the absorption kinetics of FLUand prodrug were investigated by intramuscular administration of either FLU base or FLU-D in sesame oil to groups of rats. The quantitative data suggested the involvement of the lymphatic system in the presystemic absorption of FLU and FLU-D after intramuscular administration of FLU-D in sesame oil. Finally, intravenous or intramuscular pharmacokinetics of FLU and four esters were investigated in dogs. The results showed that the chain length affected the kinetics of both FLU and the ester prodrugs. A pharmacokinetic model (s) was developed to simulate the disposition of FLU-D and the formation of FLU after either intravenous or intramuscular administration of FLU-D. Satisfactory fits of the simulated profiles with the observed data implies that the prolonged elimination profiles of FLU observed after intravenous administration could be rate limited by the ester chain length dependent distribution or redistribution of the prodrug from poorly perfused (fatty) deep compartments and subsequent hydrolysis in more highly perfused tissues while the ultimate rate limiting step in the absorption kinetics of FLU and prodrug after intramuscular administration could be the slow partitioning out of prodrug from the oily deposits at the injection sites and surrounding tissues such as proximal lymph nodes with the subsequent hydrolysis of the ester group in the body.

Thesis (M.S.)--Northern Michigan University, 2009. / Bibliography: leaves 101-114.

Adherence to antipsychotic medication in schizophrenia has been shown to predict symptom exacerbations; however, adherence remains poor in this population. The concept of taking medication on a maintenance regime is an example of prospective memory (PM). The current investigation is comprised of three studies in which 59 outpatients diagnosed with schizophrenia completed a comprehensive assessment including measures of PM, executive functioning, comprehension of medication instructions, insight into the need for medication, and environmental variables supporting adherence. An objective measure of medication adherence was also collected during a one-month baseline period. In study 1, medication adherence was conceptualized as a PM task and variables for predicting adherence based on PM literature were examined. Of the hypothesized variables, the interactive effect of PM ability and comprehension of medication instructions was the only predictor of adherence to antipsychotic medication. Comprehension of medication instructions alone was the only predictor of adherence to total psychotropic medication regime. Study 2 investigated the role of executive functions in the awareness of PM deficits and use of compensatory strategies. Results indicated that patients with poorer executive skills were less reliable in their report of PM ability compared to performance on PM measures. However, both fair and poor executive functioning groups reported similar use of compensatory strategies. Lastly, the third study manipulated the specificity of retrieval context for a 5-day habitual PM task intended to mimic medication-taking. The aim of this investigation was to examine the effect of retrieval context specificity and executive functioning on task performance. Results demonstrated that patients categorized as fair executive functioning completed significantly more days of the habitual task than patients categorized as poor executive functioning. There was no difference in performance between patients receiving greater retrieval context specificity versus patients receiving a general context. However, there was a trend for individuals with fair executive functioning to benefit from greater retrieval context specificity, implying that a minimum level of executive skill may be necessary for individuals to recognize the risk of a restricted retrieval interval and/or mobilize additional resources for encoding. Clinical implications are discussed. / text

Objective The study is to explore the relationship between antipsychotics and blood glucose level or lipid level of patients with mental illness in psychiatric outpatient clinic of Queen Mary Hospital. Participants and Methods Case reviews through Clinical Management System were carried out. Total 108 psychotic cases involved in the study. 24 were excluded as the patients did not have any treatment of antipsychotics. 84 patients were qualified for review. 40 females and 68 males involved. Their ages are between 13 and 68. Patients’ demographics information, blood glucose level or lipid level were retrieved. Some important findings are also noted. Data collection carried in May 2014. Results There are no significant changes in fasting blood glucose or lipid level for either typical or atypical antipsychotics. We found that the frequency of checking blood glucose or lipid level was too low and not regular. Risperidone and Olanzapine are the most commonly used in this psychiatric outpatient clinic. Moreover, 9 cases change from psychosis to Paranoid type schizophrenia. The most frequent diagnosis in the clinic is Paranoid type schizophrenia. 36 cases, one third of the samples, are diagnosed as Paranoid type schizophrenia. Conclusions Although we cannot conclude the effect of antipsychotics on blood glucose level or lipid level of patients with mental illness, there is an increasing concern about antipsychotics leading to metabolic problems through the case reviews. We suggest that routine physical health screening, guidelines setting up, predictors should be carried out in the clinic. / published_or_final_version / Psychological Medicine / Master / Master of Psychological Medicine