Date of Award

2010

Degree Type

Dissertation

First Advisor

Stephen Kogut

Abstract

Schizophrenia is a serious mental illness characterized by debilitating effects including, hallucinations, delusions, disordered speech and abnormal thought processes. Due to its chronic nature, and early onset, schizophrenia can cause extreme disruption to patients' lives, often with devastating and lasting effects on individuals and their families. In the past 10-15 years, a number of new pharmacological treatments, referred to as atypical antipsychotics, have emerged for the management of schizophrenia. The purpose of this dissertation was to compare the effectiveness of the atypicals within class, and also in comparison to older antipsychotic agents. Antipsychotic treatment was examined with respect to all cause treatment discontinuation. Cox regression was used to assess the independent effects of antipsychotic exposure, while adjusting for a number of potential confounders. The effects of antipsychotic exposure were also evaluated with respect to both cardiorespiratory arrest and acute myocardial infarction using an extended Cox regression model. Lastly, a nested case-control study design was used to examine factors associated with re-hospitalization. The main findings included statistically significant differences in the rate of treatment discontinuation for both high and low potency first generation antipsychotics (FGAs) versus initial treatment with risperidone. Additionally, the atypicals, paliperidone and ziprasidone, both had statistically significant higher rates of discontinuation compared with patients who initiated treatment with risperidone. No observed differences in the risk of cardio-respiratory arrest were observed between antipsychotic exposures. The comparative risk of acute myocardial infarction, relative to olanzapine exposure, was significantly lower in association with exposure to both aripiprazole, and with risperidone exposure. In comparison to re-hospitalization following treatment with risperidone, the odds of re-hospitalization were 20% higher in patients treated with aripiprazole, almost two-fold higher in patients receiving atypical antipsychotic combination therapy, 20% higher in the high potency first generation antipsychotic group, and in patients receiving lithium. An 80% increased odds of re-hospitalization was observed in patients exposed to paliperidone, and a 40% increase in both quetiapine and ziprasidone exposed patients. Statistically significant differences were observed in treatment discontinuation rates, the risk of acute myocardial infarction, and in the odds of re-hospitalization, both between atypical antipsychotics and older agents, and within atypicals. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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