Psychiatry - Theses

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    A comparison of homocysteine levels in first episode psychosis patients and age matched controls
    Stephens, Timothy Charles Bondfield ( 2007)
    Elevated serum homocysteine concentrations are neurotoxic and are strongly implicated as a risk factor for neuropsychiatric disease (Fabender, Mielke, Bertsch, & Hennerici, 1999; Kim & Pae, 1996; Kruman et al., 2000; Reutens & Sachdev, 2002). This study compares homocysteine levels in early stages psychosis patients and healthy controls. Data from 48 healthy controls were compared with 50 previously diagnosed psychosis patients, 15-25 years, and with a gender ratio males: females 7:3. Patients were outpatients or inpatients at ORYGEN Youth Health, with a diagnosis of first episode of psychosis defined as daily psychotic symptoms lasting longer than a week that could not be explained by other means such as “drug-induced” or “organic”. All subjects were interviewed to collect information relating to family psychotic history. A possible history of psychotic disease in control subjects was tested using the SCID Psych Screening Module, drug use recorded using Alcohol Use Disorders Identification Test (AUDIT) (for alcohol use), The Modified Fagerström Tolerance Questionnaire (mFTQ) (for smoking), Opiate Treatment Index (OTI) (for opiate-type drugs). Dietary and medication histories were also taken. Blood tests were performed to determine serum homocysteine, serum folate, red blood cell folate and serum vitamin B12 levels. An independent sample t test to compare homocysteine levels in patients and controls was performed. Serum homocysteine levels were significantly higher for patients (M = 12.9, S.D. = 3.6) than controls (M = 11.1, S.D. = 2.7) (t(96) = 2.7, p = 0.007, two-tailed). After General Linear Model (GLM) analysis it was found that group (patients or controls), and not serum folate, vitamin B12 and the T allele of MTHFR C677 polymorphism had significant effect on homocysteine levels. Thus a number of factors that may increase homocysteine levels were ruled out. Although it was not possible to obtain a complete data set for some factors (alcohol, smoking and caffeine consumption) (a weakness of the study), strengths included consecutive recruitment, minimisation of selection bias, good matching for age and gender between patients and controls, and the consideration of (serum) folate and (serum) vitamin B12 as potential confounding variables. A number of other studies have found significantly increased homocysteine levels in young patients compared with controls, particularly males. Most related studies favoured the homocysteine-psychosis link. The probability of symptomatic recovery is very high (80-90%) after treatment for first episode psychosis (Robinson et al., 1999) and delayed treatment, but prolonged duration of treatment is associated with poorer response in treatment and worse outcome (Malla & Norman, 2002). This justifies studying homocysteine levels and cognitive function in that first period of psychosis. This research offers evidence for the importance of serum homocysteine levels as showing involvement in the etiology of psychosis. Lowering homocysteine may have a beneficial effect on symptoms and cognitive dysfunction in psychotic illness. Two randomised controlled trials have demonstrated benefit in psychotic illness of giving folate and consequently reducing homocysteine.(Godfrey & Toone, 1990; Levine et al., 2006b). Benefits of taking folate were found in both trials for both cognition and psychotic symptoms. By reducing homocysteine levels early in the illness, some of the excess cardiovascular mortality may be prevented. Secondary prevention of CVD does not appear to influence outcome (Hermann, Herrmann, & Obeid, 2007), so the right time to intervene and reduce risk would appear to be early in the course of psychosis. Additionally, by lowering homocysteine cognitive functioning and psychotic symptoms may be improved (Levine et al., 2006b).
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    Depot medications and the treatment of schizophrenia in community psychiatry
    Lambert, Timothy John Robert ( 2005)
    Since their introduction in the 1960s, depot antipsychotics have played a substantive role in the pharmacological management of patients with schizophrenia in Australia. During the 1990s, among radical changes to the structure and function of community services in the State of Victoria, a new generation of improved oral antipsychotics was introduced. The latter were anticipated to replace older antipsychotic medications. This thesis examines the impact these changes have had on depot prescribing in community psychiatric settings. It tests the hypothesis that due to widespread concerns over the consequences of non-adherence that frequently accompany the use of all oral antipsychotics, depot agents will maintain a key place in pharmacotherapy. The research is based on Australian data taken from community care teams in Victoria, complemented in one study with data from Western Australia. The prescribing patterns data indicate that between 1998 and 2003 substantial changes in the use of antipsychotics have occurred. The results show a rapid increase in second generation antipsychotics from 38 percent to 78 percent over the five year period of the study. Over the same time, first generation antipsychotics fell from 27 percent to 3 percent of prescriptions. Prescriptions of depot agents also fell, but by a much lesser amount, from 46 percent to 29 percent of prescriptions, a level close to the absolute level of non-adherence proposed in the literature. This supports a further hypothesis that depot antipsychotics use will stabilise at a level close to the absolute level of non-adherence. The findings also indicate that from the perspective of initially distinct prescribing practices in different services, there has been a convergence of prescribing trends towards a common level of use for each group of antipsychotic medications studied. Both depot and newer oral antipsychotics demonstrate a high degree of prescribing stability over time, which is found to be inversely related to the risk of admission for population of patients considered. The clinical application of depots is effected by factors relating to the Service, the range of medications available and, characteristics of the Patient. Four studies were undertaken to explore the likely impact of these influences on community prescribing. The first shows that community treatment orders are used with depot agents more than with other antipsychotics. This supports the hypothesis that involuntary treatment orders facilitate the instigation of depot antipsychotics in reluctant community-treated patients. The second study shows that fewer than 10 percent of patients meet non-adherence criteria of less than 75 percent adherence, that an inverse relationship exists between depot adherence and hospital admission and, a critical level of depot adherence of less than 85 percent is predictive of admission with respect to this population. These findings support the decision of clinicians who prescribe depots with the expectation they will lead to better adherence. The third and fourth studies examine the attitudes of mental health professionals and depot treated patients, respectively. Differences in critical attitudes towards depot antipsychotics between professionals and between services are described. Additionally, patient attitudes to depots, assessed through a pilot satisfaction survey, indicate that only a minority of patients (46 percent) are clearly dissatisfied with their depot medications. This is at odds with the negative attitudes towards depots found among many of the clinical staff. In conclusion, the thesis demonstrates that depot antipsychotics remain an important component of the pharmacotherapy of people with schizophrenia in community psychiatric settings in Victoria. For multi-disciplinary clinical care teams their utility lies in addressing non-adherence, and so preventing relapse and rehospitalisation, and the subsequent, often widespread, costs that ensue.