Psychostimulant dependence is a major public health issue in many parts of the world associated with a wide range of psychological, medical and social problems. Psychosocial interventions are the mainstay of treatment for psychostimulant problems, although their effectiveness is compromised by poor uptake and compliance. Despite increasing knowledge of the neurobiological consequences of psychostimulant use, no medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Modafinil is a non-amphetamine type psychostimulant that may have potential as an agonist pharmacotherapy for psychostimulant dependence. The aim of this thesis was to examine the safety, efficacy and cost-effectiveness of modafinil 200 mg/day over ten weeks plus a four session brief CBT intervention for methamphetamine and cocaine dependence through two concurrent randomised placebo controlled trials. There were no statistically significant differences between modafinil and placebo in treatment retention, medication adherence, psychostimulant abstinence, psychostimulant craving or severity of psychostimulant dependence. Methamphetamine-dependent subjects tended to provide more illicit psychostimulant negative urine samples while in treatment than those who received placebo. There appeared to be a reduction in self-reported days of psychostimulant use among methamphetamine-dependent subjects who received modafinil compared to placebo, but the effect size was too small to be statistically significant in this sample. The reduction in self-reported psychostimulant use did reach statistical significance in methamphetamine-dependent subjects with no other substance dependence. Uptake of counselling was the most significant predictor of reduced psychostimulant use post treatment, and the addition of counselling improved the cost-effectiveness of modafinil relative to placebo. Modafinil appeared to be safe, well-tolerated, and non-reinforcing in this treatment population. Compared to placebo, there was a significant increase in weight in subjects who completed the 10-week course of treatment, and a significant decrease in systolic blood pressure in methamphetamine-dependent subjects who received modafinil. The results support further trials of modafinil in methamphetamine-dependent patients, although future trials in cocaine-dependent patients from this treatment population were not likely to be viable. Modafinil appeared to be modestly effective in reducing, but not stopping, methamphetamine use in selected patients. Multi-centre trials with larger sample sizes, and measures sensitive enough to detect quantitative changes in psychostimulant use would be needed to confirm the findings. Blood pressure and weight may be important indicators of clinical outcome, and warrant particular attention in future trials, particularly given the cardio-toxicity of both methamphetamine and cocaine. Strategies to enhance medication adherence including a higher dose and counselling adherence are recommended to improve outcomes. Given the predominance of behavioural and psychosocial factors in psychostimulant dependence, it is likely that the role of medications such as modafinil will be as an adjunct to psychosocial therapy.

Opioid dependence is a complex and persistent disorder with a high mortality rate and severe impact on health and social situation. It is associated with much harm, including the transmission of blood-borne bacterial and viral infections, self-harm, traumatic injury and drug overdose. All of these harms carry a risk of death, and accordingly, mortality rates in opioid-dependent people are many times higher than those in the general population of the same age and sex. One of the more commonly used strategies for reducing the risks of opioid dependence is the provision of maintenance treatment. In Australia, available maintenance treatments include methadone, buprenorphine, oral naltrexone, and the unregistered sustained-release formulation of naltrexone, naltrexone implants. This thesis reports on a range of data collections and study designs to investigate the levels, predictors and causes of mortality in opioid-dependent persons entering methadone, buprenorphine and naltrexone maintenance treatment in Australia. The studies used data linkage to examine mortality rates and causes of death in a longitudinal cohort of the early entrants to the NSW methadone program, examined the predictors of mortality (particularly the impact of methadone and buprenorphine treatment) using survival analysis in a longitudinal cohort study, compared national mortality rates between methadone, buprenorphine and naltrexone maintenance treatments in a cross-sectional analytic study, and used a small case series of coronial cases to examine whether death from opioid overdose was possible in a recipient of a naltrexone implant. This thesis demonstrates that mortality rates as a whole and from particular causes of death are many times higher in Australian opioid-dependent subjects than the general population, exposure to methadone or buprenorphine maintenance treatment significantly reduced mortality in a sample of opioid-dependent subjects, naltrexone treatment appears to have higher mortality than both methadone and buprenorphine maintenance treatments, and fatal opioid overdose while in receipt of sustained-release naltrexone treatment is possible. These results support longer retention in and repeated access to methadone and buprenorphine maintenance treatments in order to reduce mortality in opioid-dependent people, and greater regulation of the access to and more rigorous monitoring of the mortality associated with oral and sustained-release naltrexone maintenance treatments.

Asymmetric dependence (AD) is defined as dependence that differs across opposing regions of the joint return distribution. Recent evidence of AD between equity returns suggests that dependence can be decomposed into a linear component, captured by the correlation matrix, and a higher order component. When these higher order terms are characterised by increased correlation in bear or bull markets, the effectiveness of diversification strategies is reduced. To the extent that an investor is unable to completely diversify these higher order terms of dependence, it follows that they should be reflected in asset prices and managed explicitly during the portfolio construction process. The aim of this thesis is to determine the extent of AD amongst asset returns, to investigate whether AD is priced and to develop a means of managing AD in the portfolio. I justify the existence of AD and the separation of AD from linear dependence via the bivariate Edgeworth expansion, finding that the joint return distribution may be described by an infinite number of higher order co-moments. Correlation (and hence β) describes one dimension of an infinite number of higher dimensions describing dependence. To determine the importance of AD in finance, I first develop measures that can detect AD independent of the level of linear dependence and idiosyncratic risk. These measures are used to determine the extent of AD amongst US stock returns and the market, to obtain an understanding of how AD changes through time and to re-examine the evidence of AD between equity portfolios. By measuring AD separate from linear dependence, I demonstrate several findings. First, I find evidence of non-stationary AD that can exists irrespective of the magnitude of linear dependence, measured by β. This time-varying AD consists of both significant upper tail dependence (UTD) and significant lower tail dependence (LTD), although LTD is found to occur more frequently than UTD, especially for small stocks and stocks displaying high idiosyncratic risk. Significant time-varying AD is also detected between domestic equity indices and international equity markets, implying that if a portfolio is weighted towards certain industries or countries, portfolio construction methods may need to be adjusted in order too meet risk and return targets, particularly if future AD cannot be adequately forecasted. Next, I investigate whether AD is priced in US equities using the Fama and MacBeth (1973) regression methodology in conjunction with my β invariant AD metrics. I find that AD is as important as linear dependence in explaining the variation in returns. In particular, a positive relationship between LTD and return is found. I document an AD risk premium of 2.7% pa, compared to a β risk premium of 6.18% pa. The AD risk premium increases to 6.9% pa for stocks with significant LTD. This result holds after controlling for size, book-to-market ratio, downside β and coskewness. I also find past AD is a significant variable in predicting the future returns of small firms, whilst neither AD nor linear dependence predict the future returns of large firms. I subsequently demonstrate a means of incorporating AD structures during the portfolio construction process using copula functions. I then investigate how asymmetric return dependencies affect the efficient frontier and subsequent portfolio performance under a dynamic rebalancing framework. By considering the problem of tactically allocating a small set of domestic equity indices, I demonstrate several findings. First, I show that a Mean-Variance efficient frontier differs from the efficient frontier constructed under AD. Constructing paper portfolios based upon these differences, I find that real economic value lies in correctly accounting for AD structures. The primary source of this economic value stems from the ability to better protect portfolio value and reduce the size of any erosion in return relative to the normal portfolio. Finally, I document the benefits of actively managing AD during the portfolio construction process and determine a number of portfolio management principles required to successfully manage AD. I illustrate that managing asymmetry risk in a portfolio of international equity indices results in increased return, decreased risk and decreased transaction costs. I show that in order to yield these benefits, investors must actively and dynamically manage their portfolio. Furthermore, I illustrate that the ability to short-sell assets provides most of the benefits described.

Opioid dependence is a complex and persistent disorder with a high mortality rate and severe impact on health and social situation. It is associated with much harm, including the transmission of blood-borne bacterial and viral infections, self-harm, traumatic injury and drug overdose. All of these harms carry a risk of death, and accordingly, mortality rates in opioid-dependent people are many times higher than those in the general population of the same age and sex. One of the more commonly used strategies for reducing the risks of opioid dependence is the provision of maintenance treatment. In Australia, available maintenance treatments include methadone, buprenorphine, oral naltrexone, and the unregistered sustained-release formulation of naltrexone, naltrexone implants. This thesis reports on a range of data collections and study designs to investigate the levels, predictors and causes of mortality in opioid-dependent persons entering methadone, buprenorphine and naltrexone maintenance treatment in Australia. The studies used data linkage to examine mortality rates and causes of death in a longitudinal cohort of the early entrants to the NSW methadone program, examined the predictors of mortality (particularly the impact of methadone and buprenorphine treatment) using survival analysis in a longitudinal cohort study, compared national mortality rates between methadone, buprenorphine and naltrexone maintenance treatments in a cross-sectional analytic study, and used a small case series of coronial cases to examine whether death from opioid overdose was possible in a recipient of a naltrexone implant. This thesis demonstrates that mortality rates as a whole and from particular causes of death are many times higher in Australian opioid-dependent subjects than the general population, exposure to methadone or buprenorphine maintenance treatment significantly reduced mortality in a sample of opioid-dependent subjects, naltrexone treatment appears to have higher mortality than both methadone and buprenorphine maintenance treatments, and fatal opioid overdose while in receipt of sustained-release naltrexone treatment is possible. These results support longer retention in and repeated access to methadone and buprenorphine maintenance treatments in order to reduce mortality in opioid-dependent people, and greater regulation of the access to and more rigorous monitoring of the mortality associated with oral and sustained-release naltrexone maintenance treatments.

Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references (p.124-149).

Thesis (Ph.D.)--Bowling Green State University, 2008. / Document formatted into pages; contains xii, 166 p. Includes bibliographical references.

Thesis (Ph. D.)--regon State University, 1992. / Typescript (photocopy). Includes bibliographical references (leaves 83-94). Also available on the World Wide Web.

Thesis (Ph.D.)--Ohio University, November, 2007. / Title from PDF t.p. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Unnumbered leaves at back are permission forms for use of information from Consulting Psychologists Press, Inc. Typescript. Vita. Includes bibliographical references (leaves 117-132). Also available on the Internet.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains ix, 70 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 42-47).