Psychiatry - Research Publications

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    Corrigendum: Implementation of Therapeutic Virtual Reality Into Psychiatric Care: Clinicians' and Service Managers' Perspectives.
    Chung, OS ; Robinson, T ; Johnson, AM ; Dowling, NL ; Ng, CH ; Yücel, M ; Segrave, RA (Frontiers Media SA, 2022)
    [This corrects the article DOI: 10.3389/fpsyt.2021.791123.].
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    N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial.
    Sarris, J ; Byrne, G ; Castle, D ; Bousman, C ; Oliver, G ; Cribb, L ; Blair-West, S ; Brakoulias, V ; Camfield, D ; Ee, C ; Chamoli, S ; Boschen, M ; Dean, OM ; Dowling, N ; Menon, R ; Murphy, J ; Metri, N-J ; Nguyen, TP ; Wong, A ; Jordan, R ; Karamacoska, D ; Rossell, SL ; Berk, M ; Ng, CH (Elsevier BV, 2022-07-13)
    OBJECTIVE: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD. METHODS: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit. RESULTS: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment. CONCLUSION: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
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    Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study
    Sarris, J ; Byrne, GJ ; Oliver, G ; Cribb, L ; Blair-West, S ; Castle, D ; Dean, OM ; Camfield, DA ; Brakoulias, V ; Bousman, C ; Dowling, N ; Ee, C ; Murphy, J ; Menon, R ; Berk, M ; Chamoli, S ; Boschen, M ; Ng, CH (CAMBRIDGE UNIV PRESS, 2022-10-21)
    BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
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    Implementation of Therapeutic Virtual Reality Into Psychiatric Care: Clinicians' and Service Managers' Perspectives
    Chung, OS ; Robinson, T ; Johnson, AM ; Dowling, NL ; Ng, CH ; Yucel, M ; Segrave, RA (FRONTIERS MEDIA SA, 2022-01-04)
    Objectives: Virtual reality (VR) has emerged as a highly promising tool for assessing and treating a range of mental illnesses. However, little is known about the perspectives of key stakeholders in mental healthcare, whose support will be critical for its successful implementation into routine clinical practise. This study aimed to explore the perspectives of staff working in the private mental health sector around the use of therapeutic VR, including potential implementation barriers and facilitators. Methods: Semi-structured qualitative interviews were conducted with cross-disciplinary clinicians (n = 14) and service managers (n = 5), aged 28-70 years working in a major private mental health hospital in Victoria, Australia. Transcripts were analysed using general inductive coding to allow themes to naturally emerge. Results: Three major themes were identified: clinical factors (four subthemes), organisational factors (five subthemes), and professional factors (three subthemes). The themes encompassed enabling factors and potential barriers that need to be addressed for successful implementation of VR. Clinical factors highlighted the influence of knowledge or perceptions about appropriate clinical applications, therapeutic efficacy, safety and ethical concerns, and patient engagement. Organisational factors emphasised the importance of service contexts, including having a strong business case, stakeholder planning, recruitment of local opinion leaders to champion change, and an understanding of resourcing challenges. Professional factors highlighted the need for education and training for staff, and the influence of staff attitudes towards technology and perceived usability of VR. Conclusions: In addition to enabling factors, potential implementation barriers of therapeutic VR were identified, including resourcing constraints, safety and ethical concerns, negative staff attitudes towards technology and VR system limitations. Future dissemination should focus on addressing knowledge and skills gaps and attitudinal barriers through development of clinical guidelines, training programs, and implementation resources (e.g., adoption decision tools, consultation opportunities).
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    Are Australian Mental Health Services Ready for Therapeutic Virtual Reality? An Investigation of Knowledge, Attitudes, Implementation Barriers and Enablers
    Chung, OS ; Johnson, AM ; Dowling, NL ; Robinson, T ; Ng, CH ; Yuecel, M ; Segrave, RA (FRONTIERS MEDIA SA, 2022-02-04)
    Therapeutic virtual reality (VR) has the potential to address the challenges of equitable delivery of evidence-based psychological treatment. However, little is known about therapeutic VR regarding the perspectives and needs of real-world service providers. This exploratory study aimed to assess the acceptability, appropriateness, and feasibility of therapeutic VR among clinicians, managers, and service staff working in mental healthcare and explore potential implementation barriers and enablers. Eighty-one staff from a network of private psychiatric hospitals in Victoria, Australia (aged M + SD: 41.88 + 12.01 years, 71.6% female; 64% clinical staff) completed an online survey, which included the Acceptability of Intervention Measure (AIM), Appropriateness of Intervention Measure (IAM), and Feasibility of Intervention Measure (FIM). While 91% of participants had heard about VR technology, only 40% of participants had heard of therapeutic VR being used in mental healthcare, and none had used therapeutic VR in a clinical setting. Most participants perceived VR to be acceptable (84%), appropriate (69%), and feasible (59%) to implement within their role or service and envisioned a range of possible applications. However, participants expressed concerns regarding safety, efficacy, and logistical challenges across clinical settings. Findings suggest a strong interest for therapeutic VR among Australian mental health providers working in the private system. However, dissemination efforts should focus on addressing identified barriers to ensure mental health providers are adequately informed and empowered to make implementation decisions.
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    Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial
    Dean, OM ; Maes, M ; Ashton, M ; Berk, L ; Kanchanatawan, B ; Sughondhabirom, A ; Tangwongchai, S ; Ng, C ; Dowling, N ; Malhi, GS ; Berk, M (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2014-12)
    While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.
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    Physical comorbidities in private psychiatric inpatients: Prevalence and its association with quality of life and functional impairment
    Nadjidai, SE ; Kusljic, S ; Dowling, NL ; Magennis, J ; Stokes, L ; Ng, CH ; Daniel, C (WILEY, 2020-12)
    The aim of this study was to examine the association between physical health conditions and quality of life and functioning in private psychiatric inpatients. We sought to determine whether quality of life and functioning was poorer in individuals with physical comorbidity compared to those without. A quantitative correlational descriptive design was utilized. Seventy patients were included in sequential order within a week of admission to hospital. Participants completed the SF-36 survey, and the corresponding hospital records were audited. The STROBE guidelines were followed in the reporting of this research. The study found that 64.3% (45/70) of participants had one or more comorbid physical health conditions, primarily cardiovascular, respiratory, musculoskeletal, endocrine and medically unexplained conditions or syndromes. Chronic pain was experienced by 40% (28/70) of participants, and 47.6% (33/70) were found to be overweight or obese. Tobacco smoking and obesity were risk factors associated with physical comorbidity (P = 0.02 and P < 0.001, respectively). Quality of life and functioning were poorer in those with physical health conditions, particularly in the SF-36 domains of bodily pain, physical functioning and general health (P < 0.001, P = 0.003 and P = 0.005, respectively). Physical health conditions were largely prevalent, and quality of life and functioning were poorer in those with physical comorbidities. The implementation of clinical guidelines for the monitoring of physical health has been proposed as well as a dedicated physical health nursing role. Continuation of integrative programmes focusing on both physical and mental health may also benefit patients in this setting.
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    Efficacy of adjunctive Garcinia mangostana Linn (mangosteen) pericarp for bipolar depression: study protocol for a proof-of-concept trial
    Ashton, MM ; Berk, M ; Ng, CH ; Hopwood, M ; Dodd, S ; Turner, A ; Brown, E ; Jacka, FN ; Cotton, SM ; Khoo, J-P ; Chatterton, ML ; Kavanagh, BE ; Nadjidai, SE ; Lo Monaco, SL ; Harvey, BH ; Sarris, J ; Malhi, GS ; Dowling, NL ; Dean, OM (ASSOC BRASILEIRA PSIQUIATRIA, 2019)
    OBJECTIVE: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. METHODS: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. CONCLUSION: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.
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    Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial
    Kavanagh, BE ; Williams, LJ ; Berk, M ; Turner, A ; Jackson, HJ ; Mohebbi, M ; Kanchanatawan, B ; Ashton, MM ; Ng, CH ; Maes, M ; Berk, L ; Malhi, GS ; Dowling, N ; Singh, AB ; Dean, OM (ASSOC BRASILEIRA PSIQUIATRIA, 2020)
    OBJECTIVE: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). METHODS: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. RESULTS: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). CONCLUSION: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. CLINICAL TRIAL REGISTRATION: ACTRN12612000283875.