Treatment

Treatment

Stream Description

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One in every two people will develop a mental health or substance use disorder during their lifetime. Our treatment research aims to develop and evaluate the efficacy of novel interventions to treat these disorders as well as their combination. Our research thus far has focused on the testing of psychotherapies and pharmacotherapies for individuals who have both a substance use disorder and the most common mental disorders including anxiety, depressive and psychotic disorders.

 

 

Ongoing Projects

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Randomized controlled trial of N-acetylcysteine for drug relapse prevention

Project Members: Prof Sudie Back
Peter Kalivas
Funding Body: United States Department of Defense
Description:

With the increased number of military veterans returning from conflicts in Afghanistan and Iraq diagnosed with posttraumatic stress disorder (PTSD), there is a high vulnerability of these individuals to develop a substance use disorder (SUD). While there have been a host of studies focused largely on dopaminergic mechanisms of drug reward, they have not led to the development of adequate treatments for either preventing people diagnosed with PTSD from developing SUDs or for treating comorbid PTSD/SUDs. N-acetylcysteine (NAC) is an amino acid that may help to treat comorbid PTSD/SUD by increasing extracellular glutamate in the nucleus accumbens, a key brain structure in the craving circuitry. Restoring basal glutamate levels by pretreating with NAC may blunt the release of presynaptic glutamate. The aim of this studyis to establish a proof-of-concept trial protocol for measuring drug craving and relapse in Veterans suffering from comorbid PTSD/SUDs and to determine the efficacy of NAC in preventing relapse and reducing drug craving and PTSD symptoms among Veterans with comorbid PTSD/SUDs.

Project Contacts: Prof Sudie Back
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Social well-being and engaged living (SWEL) intervention for Australian youth at risk of mental health and other adverse outcomes

Dr Helen Stain, Dr Christopher Jackson, Professor Rhoshel Lenroot, Dr Georgie Paulik, Dr Patrick McElduff, Dr Luke Wolfenden
Funding Body: National Health and Medical Research Council
Description:

Adolescence is a period of rapid physical, emotional and social growth. Young people are faced with significant developmental challenges including the establishment of a stable identity, mastery of personal relationships and the achievement of major educational and vocational goals. Many young people lack the socio-emotional skills necessary to successfully negotiate the transition through adolescence, and are at increased risk of disengaging from education, family and community. Once disengaged, youth are at risk of a range of adverse outcomes such as reduced social and community participation in young adulthood and beyond. Much of this social disadvantage could be avoided if disengaged youth had access to effective prevention and early intervention programs.

This is the first clinical trial to investigate the efficacy of a telephone delivered intervention for improving the social engagement and emotional well-being of disengaged rural and urban youth. There will be 294 youth aged 12-25 years randomised to receive either (i) 8 sessions of Social Well-being and Engaged Living intervention (SWEL), (ii) 8 sessions of Befriending, or (iii) Single Session Psycho-Education. We will engage with the Aboriginal communities in our catchment regions through consultation and collaboration; employment and training of Aboriginal youth liaison officers; consultation, liaison and education with Aboriginal key workers in the community for referral of disengaged youth. Our unique intervention aims to foster positive social and emotional skills in adolescents, to decrease the risk of adverse outcomes and promote health enhancing lifestyles. It will facilitate the resumption of education, training or employment and enhance the social inclusion of disengaged youth. Our clinical trial will increase access to effective early intervention for disengaged urban and rural youth to improve the mental health and well-being of all young Australians.

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The impact of real-time fMRI feedback on response to nicotine cues

Project Members: Prof Kathleen Brady
Mark George
Funding Body: NIH/NIDA
Description:

Nicotine dependence is the leading preventable cause of mortality in the world today. Cue-induced craving is likely to play an important role in relapse. The neural correlates of smoking cue-induced craving and extinction have been elucidated using fMRI. Recent advances make it possible to utilize real-time fMRI (rtfMRI) feedback to modify behavior, cognitions and regional brain activity. The purpose of this study is to develop the imaging parameters, brain-computer interface and standardized procedures for using rtfMRI with visual feedback to help nicotine-dependent individuals decrease craving when presented with smoking cues. The exploratory nature of this study requires a phased approach. Phase 1 will focus on the development of the technology and study paradigm. In order to proceed to Phase 2, there must be convincing evidence that a substantial proportion of nicotine-dependent individuals can manipulate brain activity in critical brain regions associated with smoking cue-induced craving based on rtfMRI visual feedback. If this is established, a controlled comparison and duration of effect will be explored in Phase 2. This project will set the stage for clinical trials investigating a very innovative approach to the treatment of nicotine dependence and other substance use disorders. The study will provide critical information about optimal techniques, durability and "transferability" of the effects to situations outside of the scanner. The findings of this study can be used to inform the design of a clinical trial to investigate the use of rtfMRI neuromodulation training in smoking cessation.

Project Contacts: Prof Kathleen Brady
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Update and revision of the national comorbidity guidelines

Funding Body: Australian Government Department of Health
Description:

In 2007 the Australian Government Department of Health and Ageing funded the development of “Guidelines on the management of co-occurring alcohol and other drug and mental health conditions in alcohol and other drug treatment settings(Mills, et al., 2009). The aim of the Guidelines was to provide alcohol and other drug (AOD) workers with evidence-based information on the management of comorbid mental health conditions in AOD treatment settings. The Guidelines have been hugely popular – since publication in December 2009, over 10,000 hard-copies and electronic copies have been distributed to clinicians and treatment services across Australia, and it is a recommended text for students studying TAFE courses in alcohol, other drugs and mental health. Research pertaining to the management and treatment of comorbidity has grown considerably since this time, and as such, this project will update and revise the Guidelines to bring them up to date with the most current evidence.

Project Contacts: Dr Christina Marel

Completed Projects

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A brief intervention for traumatised clients of alcohol and other drug treatment services

Dr Claudia Sannibale
Funding Body: NSW Health Drug and Alcohol Research Grants Program
Description:

Trauma exposure and post traumatic stress disorder (PTSD) are highly prevalent among clients of alcohol and other drug (AOD) treatment services. There is expert agreement that to improve the outcomes of individuals with substance use disorders (SUD) who have experienced trauma, AOD treatment services need to incorporate trauma-specific interventions. There are however, very few evidence-based treatment options for AOD clients who have experienced trauma and/or have PTSD. Those that do exist possess a number of characteristics that inhibit their ability to be implemented in AOD services; they tend to be lengthy, treatment retention is relatively poor, and they require extensive training and clinical supervision. For these reasons, many AOD clinicians are not able, or willing, to implement these interventions in clinical practice. A brief intervention (BI) for trauma-related symptoms may be more attractive, feasible and sustainable to both clients and AOD workers. BI’s are less time and resource intensive, and they may be applied across a variety of settings, by a range of clinicians, with minimal training. The present study sought to pilot test, in an uncontrolled trial, the feasibility of a brief intervention for traumatised clients of AOD treatment services. The study findings provide preliminary evidence that brief psychoeducation for traumatised clients of AOD services is safe and appears to have some benefit in relation to PTSD symptoms. Severity of PTSD symptoms significantly decreased from baseline to 1-week follow up and these reductions were retained through to the 3 month follow up. However, while PTSD symptoms decreased, patients were still experiencing symptoms at severe levels.  There was also no change in relation to post traumatic cognitions, and initial improvements in substance use were not maintained. Thus, the brief intervention may best be conceptualised as a “stepping stone” to further trauma treatment. Further research examining the brief intervention in the context of stepped-care approaches to treatment may be beneficial.

Project Contacts: Ms Philippa Ewer
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Australian Treatment Outcome Study

Prof Shane Darke, Prof Michael Lynskey, Ms Joanne White
Funding Body: National Health and Medical Research Council
Description:

Heroin dependence is remarkably persistent, and in many cases it is a lifelong condition with a high mortality rate. Yet, the natural history of heroin dependence has rarely been studied. The Australian Treatment Outcome Study (ATOS) is a landmark Australian cohort study examining outcomes from heroin dependence. 615 participants were recruited to the study in 2001-2002 and followed up over three years. The 11-year follow-up commenced in 2012, making it one of the longest and most comprehensive prospective follow-up of Australian heroin users. An 11-year follow-up presents the unique opportunity to examine: Mortality rates, remission rates, criminal histories and levels of psychopathology; predictive factors of long term remission, mortality, criminality; and the health service utilisation associated with heroin use careers.

Seventy percent (n=431) of the original 615 participants completed the 11-year follow-up; a further 10% (n=63%) of participants were deceased. The proportion of participants who reported using heroin in the preceding month decreased significantly from baseline (98.7%) to 36-month follow-up (34.0%; odds ratio=0.01; 95% confidence interval=0.00, 0.01) with further reductions evident between 36 months and 11 years (24.8%). However, one in four continued to use heroin at 11 years, and close to one-half (46.6%) were in current treatment. The reduction in current heroin use was accompanied by reductions in risk taking, crime and injection-related health problems, and improvements in general physical and mental health. The relationship with treatment exposure was varied. Major depression was associated consistently with poorer outcome.

Project Contacts: Dr Christina Marel
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Buspirone treatment for marijuana dependence

Project Members: Prof Kathleen Brady
Aimee McRae-Clark
Funding Body: NIH/NIDA
Description:

Marijuana is the most commonly used illicit drug, yet few clinical trials have evaluated pharmacotherapy treatments for marijuana dependence. The purpose of this study was to evaluate the efficacy of buspirone, a partial 5-HT1A agonist, for treatment of cannabis dependence. 175 cannabis-dependent adults were randomised to receive either up to 60 mg/day of buspirone (n = 88) or placebo (n = 87) for 12 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests.

Participants in both groups reported reduced cannabis craving over the course of the study; however, buspirone provided no advantage over placebo in reducing cannabis use. Significant gender by treatment interactions were observed, with women randomised to buspirone having fewer negative urine cannabinoid tests than women randomised to placebo (p = 0.007), and men randomised to buspirone having significantly lower creatinine adjusted cannabinoid levels as compared to those randomised to placebo (p = 0.023). An evaluation of serotonin allelic variations did not find an association with buspirone treatment response.

Project Contacts: Prof Kathleen Brady
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D-Cycloserine facilitation of cocaine-cue extinction

Project Members: Prof Kathleen Brady
Funding Body: NIH/NIDA
Description:

Cocaine dependence remains a serious problem in the United States today and in spite of two decades of intense research, efficacious pharmacotherapeutic treatments have not been identified. Cocaine-associated environmental cues can elicit drug craving and exposure to cocaine-related cues is likely to be involved in relapse. Emerging data supports the role of glutamate in extinction learning. D-cycloserine (DCS), a partial glutamate agonist, facilitates extinction of associative learning in animal models of fear-conditioning and clinical studies of exposure treatment for anxiety disorders. A recent study demonstrated DCS acceleration of extinction of cocaine-induced conditioned place preference in rats (Botreau et al., 2006). Exploration of DCS in facilitating extinction of response to drug-related cues in humans is needed. This study extended these innovative and promising findings from the basic science arena and anxiety disorders field in a proof of concept investigation of DCS facilitation of extinction of response to cocaine-related cues in a human laboratory paradigm. In addition, to examine the neural substrates of extinction learning, a sub-set of individuals that were willing and eligible underwent fMRI scanning procedures before and after the extinction protocol.

Project Contacts: Prof Kathleen Brady
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Group schema therapy for the treatment of co-occurring depression and opioid dependence.

Funding Body: NSW Ministry of Health - Drug and Alcohol Research Grants Program
Description:

Heroin dependence is a chronic relapsing condition, associated with high levels of psychopathology. On entry to treatment approximately one quarter of heroin users meet criteria for Major Depression (MD). While cognitive behavioural therapy has the greatest evidence base for the treatment of MD, it makes several assumptions that don’t hold true for clients with chronic problems, such as long term drug dependence, and chronic depression. Schema therapy (ST) significantly expands on traditional cognitive behavioural treatments, and appears well suited to clients with chronic psychological disorders who have been difficult to treat. It places greater emphasis on exploring the childhood and adolescent origins of psychological problems, and on maladaptive coping styles. This study aims to pilot test, in a small randomised controlled trial, the feasibility of a group intervention for chronically depressed, opioid dependent clients of alcohol and other drug (AOD) treatment services.

Project Contacts: Dr Joanne Ross
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Healthy lifestyle intervention for cardiovascular disease risk reduction among people with psychotic disorders

Prof Jayashri Kulkarni, A/Prof Jill Williams
Funding Body: National Health and Medical Research Council
Description:

People with severe mental disorders typically experience a range of health problems; consequently, interventions addressing multiple health behaviors may provide an efficient way to tackle this major public health issue. This two-arm randomised controlled trial among people with psychotic disorders examined the efficacy of nicotine replacement therapy (NRT) plus either a face-to-face or predominantly telephone delivered intervention for smoking cessation and cardiovascular disease (CVD) risk reduction.

Following baseline assessment and completion of a common, individually delivered 90-minute face-to-face intervention, participants (n = 235) were randomised to receive NRT plus: (1) a "Healthy Lifestyles" intervention for smoking cessation and CVD risk behaviors or (2) a predominantly telephone-based intervention (designed to control for NRT provision, session frequency, and other monitoring activities). Research assistants blind to treatment allocation performed assessments at 15 weeks (mid-intervention) and 12 months after baseline.

There were no significant differences between intervention conditions in CVD risk or smoking outcomes at 15 weeks or 12 months, with improvements in both conditions (eg, 12 months: 6.4% confirmed point prevalence abstinence rate; 17% experiencing a 50% or greater smoking reduction; mean reduction of 8.6 cigarettes per day; mean improvement in functioning of 9.8 points).

The health disparity experienced by people with psychotic disorders is high. Face-to-face Healthy Lifestyle interventions appear to be feasible and somewhat effective. However, given the accessibility of telephone delivered interventions, potentially combined with lower cost, further studies are needed to evaluate telephone delivered smoking cessation and lifestyle interventions for people with psychotic disorders.

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