Using the Theoretical Domains Framework to Inform the Implementation of Therapeutic Virtual Reality into Mental Healthcare.

Evidence supporting the efficacy of therapeutic virtual reality (VR) for mental health conditions is rapidly growing. However, little is known about how best to implement VR, or the challenges perceived by treatment providers. This study aimed to (1) synthesis perspectives of staff working in private mental healthcare and (2) use the Theoretical Domains Framework (TDF) and Behaviour Change Wheel (BCW) to identify mechanisms of change targets and intervention functions to facilitate its clinical implementation. Semi-structured interviews were conducted with clinicians (n = 14) and service managers (n = 5) working in a major private mental health hospital in Victoria, Australia. Transcripts were coded using framework analysis to identify relevant TDF domains. Specific belief statements were generated and coded as a barrier and/or facilitator and thematically organised within domains. Domains were ranked for importance based on frequency, elaboration, and evidence of conflicting beliefs. Using the BCW, domains were mapped to their respective COM-B components and indicated intervention functions. A total of 11 TDF domains were identified as relevant to early-stage implementation of therapeutic VR. Three domains were judged as highly important (beliefs about consequences; environmental context and resources; knowledge), while seven domains were judged as moderately important (social/professional role and identity; emotions; skills; memory, attention, and decision processes; intentions; beliefs about capabilities; social influences). Based on current data, we propose a theory-informed roadmap to promote VR uptake in mental healthcare services. A priority for intervention development should be addressing knowledge gaps and attitudinal barriers (e.g., safety concerns) with education and training.

Corrigendum: Implementation of Therapeutic Virtual Reality Into Psychiatric Care: Clinicians' and Service Managers' Perspectives.

[This corrects the article DOI: 10.3389/fpsyt.2021.791123.].

N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial.

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.

Are Australian Mental Health Services Ready for Therapeutic Virtual Reality? An Investigation of Knowledge, Attitudes, Implementation Barriers and Enablers.

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.

Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study.

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.

Triathlon Considerations.

Triathlon is an increasingly popular sport that includes swimming, cycling, followed by running. The triathlete should not be seen merely as a cyclist who also swims and runs. Notable differences are seen in the type of bike used, training patterns, lower extremity demands, and cumulative nature of the sport. Injury prevention and treatment strategies need to take into account the triathlon distance, the type of bike used, athletic experience, prior injuries, risk factors, and a thorough understanding of the demands placed on the body through all 3 disciplines (swim, bike, and run).

Exposure therapy in a virtual environment: Validation in obsessive compulsive disorder.

Exposure and response prevention (ERP) is the current first-line psychological treatment for Obsessive-compulsive disorder (OCD). However, substantial inter-individual variability exists in treatment outcomes, including inadequate symptom improvements, and notable refusal and attrition rates. These are driven, in part, by impracticalities in simulating intrusive thoughts within clinical settings. Virtual reality (VR) offers the potential of overcoming these limitations in a manner that allows for finely controlled anxiety-provoking scenarios to be created within supportive clinical settings. To validate the potential of VR for treating contamination-based OCD, 22 patients undertook a VR ERP session and a matched session of the current gold-standard of in vivo ERP. In VR, patients were immersed within a contamination environment that permitted flexible delivery of customisable, graded exposure tasks. The VR environment utilised HTC Vive hardware, to allow for patients to both interact with, and physically move through the environment. Subjective and objective measures of distress were recorded, including heart and respiration rates. These measures indicate virtual and in vivo ERP sessions provoke consistent anxiety profiles across an exposure hierarchy. Virtual exposure was advantageous for engagement and adherence to tasks, and the therapeutic alliance was upheld. VR is a promising mechanism for ERP in contamination OCD.

Implementation of Therapeutic Virtual Reality Into Psychiatric Care: Clinicians' and Service Managers' Perspectives.

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).

Absconding from Public Mental Health Inpatient Units - Who Does it, and why?

Patients who abscond from acute inpatient psychiatric wards put themselves and others at risks of variable nature and severity. There is a limited understanding of what motivates them to do so. The research in this area is limited and predominantly outdated. To better understand the characteristics, patterns and predictors of people who abscond from hospital, this study compared absconding and non-absconding patients in a tertiary public hospital. Demographic and clinical characteristics were audited for patients who absconded (n = 159) and who did not abscond (n = 100) throughout a 2-year period. Patients who absconded in the public settings were more likely to be male, have suffered from a psychotic illness, had an increased number of psychiatric comorbidities, had a history of aggression, and used greater numbers of substances. They also had experienced homelessness, were case managed, and were managed as involuntary patients. Predictors were similar, and included involuntary legal status, greater number of substances used, greater numbers of comorbid psychiatric illnesses, polysubstance use, an absence of self-harm history, shorter duration of admission and male sex. This study has implications for the identification of those who are at greater risk of absconding from an inpatient unit. Through enhanced understanding, greater measures can be taken to minimise absconding and its associated risks.

Repetitive transcranial magnetic stimulation for major depression: A naturalistic observational study in an Australian private hospital.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depression, which is now as a mainstream treatment in clinical practice. However, there is limited data concerning its use in Australian private psychiatric hospital settings. This retrospective study examined routinely collected data of 153 inpatients, who received 20 rTMS treatments over four weeks. Primary outcomes measures were the 17-item Hamilton Depression Rating Scale (HAMD-17) and the 21-item Depression, Anxiety and Stress Scale (DASS-21). At post-treatment, response and remission rates were 54% and 28%, respectively, for the HAMD-17; and 53% response and 16% remission rates, for the DASS-21 Depression subscale, respectively. Although no gender differences were observed, younger patients demonstrated more improvements during acute rTMS but the effect was not significant after accounting for pre-treatment symptom severity. The findings of this naturalistic study suggest that an acute course of rTMS provided in private clinical settings resulted in similar response and remission rates to longer rTMS courses. Shorter rTMS courses appear to have satisfactory efficacy in treating major depression, in clinically diverse and real-world practice.

Physical comorbidities in private psychiatric inpatients: Prevalence and its association with quality of life and functional impairment.

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.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial

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.

Profiling Absconders from Public and Private Inpatient Psychiatric Units: a Comparative Analysis.

Research related to absconding and its associated risks is limited in relation to inpatients from private psychiatric units. This study aimed to compare patients who abscond from public and private psychiatric inpatient settings. Demographic data was collated on the subjects (n = 214) who all had a history of absconding. Public absconders (n = 159) were more likely to have a psychotic illness, increased number of psychiatric diagnoses, history of aggression, substance use and homelessness, when compared to private absconders. Predictors identified for private absconders (n = 55) were female gender and fewer drugs used. This study has implications for the different profiles of absconders between the public and private settings.

Cognitive effects of brief and ultrabrief pulse bitemporal electroconvulsive therapy: a randomised controlled proof-of-concept trial.

BACKGROUND: Reduction of the pulse width has been reported to improve ECT outcomes with unilateral ECT (similar efficacy, fewer cognitive side effects), but has been minimally studied for bitemporal ECT. The only study comparing brief and ultrabrief pulse bitemporal ECT found reduced efficacy for bitemporal ultrabrief compared to bitemporal brief pulse stimulation. This randomised controlled trial (RCT) aimed to test if ultrabrief pulse bitemporal ECT results in fewer cognitive side effects than brief pulse bitemporal ECT, when given at doses adjusted with the aim of achieving comparable efficacy. METHODS: Thirty-six participants were randomly assigned to receive ultrabrief (at 3 times seizure threshold) or brief (at 1.5 times seizure threshold) pulse bitemporal ECT given 3 times a week in a double-blind, controlled proof-of-concept trial. Blinded raters assessed mood and cognitive functioning over the ECT course. RESULTS: Efficacy and cognitive outcomes did not differ significantly between the two treatment groups over the ECT course. The ultrabrief pulse group performed better on a test of visual memory assessed acutely after an ECT treatment. CONCLUSIONS: This study suggests there may be a small cognitive advantage in giving bitemporal ECT with an ultrabrief pulse when dosage is increased to match the efficacy of brief pulse bitemporal ECT, but the study was underpowered to fully examine this issue.Clinical Trials Registration: www.clinicaltrials.gov, NCT00870805.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial.

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.

Efficacy of adjunctive Garcinia mangostana Linn (mangosteen) pericarp for bipolar depression: study protocol for a proof-of-concept trial

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.

Correction to: A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.

The original article [1] contained two minor errors.

A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.

BACKGROUND: A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. METHODS: A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. RESULTS: One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. CONCLUSIONS: These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. TRIAL REGISTRATION: ANZCTR ( ACTRN12612000830897 ).

Efficacy of adjunctive Garcinia mangostana Linn (mangosteen) pericarp for bipolar depression: study protocol for a proof-of-concept trial.

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.