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.

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.

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.

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.

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.

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 ).

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

OVERVIEW: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). METHODS: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. RESULTS: After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. CONCLUSION: Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

Emotion regulation difficulties in obsessive-compulsive disorder.

OBJECTIVE: Emotion regulation difficulties are implicated in psychological disorders but their role in obsessive-compulsive disorder (OCD) is unclear. Two studies examining these difficulties in OCD are presented. METHOD: A community sample (Study 1; n = 306) and a clinical OCD sample (Study 2; n = 59) completed the Difficulties in Emotion Regulation Scale (DERS) and measures of depression, anxiety, and OCD. In Study 2, the OCD sample was compared to a matched control group (n = 59, selected from Study 1). RESULTS: In Study 1, OCD was positively correlated with DERS total and subscale scores, and the DERS significantly predicted OCD severity even after accounting for age, gender, depression, and anxiety. In Study 2, emotion regulation difficulties were significantly higher in the clinical sample compared to the matched control group, even after accounting for depression and anxiety. CONCLUSION: Results showed that emotion regulation difficulties in OCD cannot simply be attributed to mood difficulties. Theoretical and treatment implications are discussed.

Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial.

OBJECTIVE: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. METHODS: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. RESULTS: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4.5, -1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [-1.7, -0.4], p = 0.017. CONCLUSION: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.

Methylphenidate in the treatment of an adolescent female with obsessive-compulsive disorder and attention deficit hyperactivity disorder: a case report.

OBJECTIVES: We describe a case whereby a 15-year-old female with treatment-resistant obsessive-compulsive disorder (OCD) was treated with methylphenidate for co-morbid attention deficit hyperactivity disorder (ADHD). The ADHD-OCD co-morbidity has often been overlooked clinically due to conflicting opinions about their underlying neurobiology and treatment options. CONCLUSIONS: In this adolescent with co-morbid ADHD and OCD, we observed that the adjunctive use of methylphenidate resulted in enhanced treatment response to both psychological and pharmacological interventions for OCD. This case highlights the need to identify and treat co-morbid ADHD in OCD cases where progress has stalled.

Effects of COMT, DRD2, BDNF, and APOE Genotypic Variation on Treatment Efficacy and Cognitive Side Effects of Electroconvulsive Therapy.

OBJECTIVES: The aim of this study was to explore the main and interaction effects of the COMT Val158Met, DRD2 C957T, BDNF Val66Met, and APOE polymorphisms on treatment efficacy and cognitive side effects of electroconvulsive therapy (ECT). METHODS: A total of 117 adult inpatients with a diagnosis of major depressive disorder recruited from 3 hospitals were administered the Montgomery-Äsberg Depression Rating Scale and a cognitive battery assessing global cognition, anterograde memory, executive function, speed and concentration, as well as retrograde memory at baseline and after ECT treatment. RESULTS: DRD2 C957T heterozygotes had 3.7 (95% confidence interval, 1.13-12.25; P = 0.032) greater odds of remission compared with CC homozygotes. Among the men, COMT Val/Val carriers had greater depressive symptom reduction compared with Met/Met carriers (Montgomery-Äsberg Depression Rating Scale percentage of reduction, 76% vs 35%; P = 0.020) but not among the women (P = 0.903) after ECT. For cognitive outcomes, an interaction effect on anterograde memory was observed between the DRD2 and BDNF polymorphisms (P = 0.016), in which carriers of the DRD2 TT and BDNF Val/Val genotypes had significantly less decline in anterograde performance than those that carried the TC and Met-allele (P = 0.001) or CC and Met-allele (P = 0.003) genotypes. However, no results withstood correction for multiple comparisons. CONCLUSIONS: These observations provide preliminary evidence supporting an association between common functional genotypic variation and ECT efficacy as well as anterograde memory side effects after ECT. Validation of these findings is required before firm conclusions can be made and clinical utility can be assessed.

A randomized controlled trial of brief and ultrabrief pulse right unilateral electroconvulsive therapy.

BACKGROUND: Some studies suggest better overall outcomes when right unilateral electroconvulsive therapy (RUL ECT) is given with an ultrabrief, rather than brief, pulse width. METHODS: The aim of the study was to test if ultrabrief-pulse RUL ECT results in less cognitive side effects than brief- pulse RUL ECT, when given at doses which achieve comparable efficacy. One hundred and two participants were assigned to receive ultrabrief (at 8 times seizure threshold) or brief (at 5 times seizure threshold) pulse RUL ECT in a double-blind, randomized controlled trial. Blinded raters assessed mood and cognitive functioning over the ECT course. RESULTS: Efficacy outcomes were not found to be significantly different. The ultrabrief group showed less cognitive impairment immediately after a single session of ECT, and over the treatment course (autobiographical memory, orientation). CONCLUSIONS: In summary, when ultrabrief RUL ECT was given at a higher dosage than brief RUL ECT (8 versus 5 times seizure threshold), efficacy was comparable while cognitive impairment was less.

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).

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.

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.

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).

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.