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Background: Early identification and intervention for mental health (MH) problems in childhood offers lifelong benefits. Many children with MH problems do not receive appropriate help. To address this need, an online universal MH screening tool, the Growing Minds Check-In for parents/caregivers (GMCI-P), was developed to provide feedback to parents on their children's MH, identify children at risk of MH problems, and link parents to evidence-based online programs/information, with the goal of facilitating parent help-seeking, and ultimately reducing the prevalence of child MH problems., Methods/design: A randomised controlled trial (RCT) with 440 parents/caregivers will be conducted to 1) examine the efficacy of GMCI-P for increasing parent help-seeking; 2) explore acceptability; and 3) cost-effectiveness. Participants will be Australian parents/caregivers with a child aged from birth to 17 years, 6 months, who will be randomly allocated to GMCI-P (intervention) or waitlist control (WLC) group, and complete baseline measures. The intervention group will complete the GMCI-P immediately, the post-GMCI-P intervention questions, a three-month and six-month follow-up. The WLC group will receive access to GMCI-P after their three-month follow-up but will not be followed up further. The primary outcome is parent help-seeking behaviour for child MH, and secondary outcomes include child MH, parenting, parent wellbeing, acceptability, cost-effectiveness, and unintended negative effects., Discussion: The results from this study will provide efficacy, acceptability and cost-effectiveness data on a universal online, parent-report child MH Check-In. These results can be used to inform public policy on universal screening for child MH., Trial Registration: ACTRN12624000098538., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties., Aims: To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD., Method: The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5-0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and 'inner tension' item 3 of the Montgomery-Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment ( n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448)., Results: In cohort 1 ( n = 68) the reduction in HAM-A score was not statistically significant: -1.4 (95% CI [-8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 ( n = 106) of -4.0 (95% CI [-10.6, -1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 ( P = 0.026) but not cohort 1 ( P = 0.96)., Conclusion: Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

Objective: To quantify the costs of hypertension diagnosis and treatment in Australia, particularly in primary care, including general practices and pharmacies., Study Design: Economic analysis; analysis of Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) data., Setting: Australia, 2012-22., Main Outcome Measure: Estimated expenditure on hypertension care (adjusted to 2022 Australian dollars), overall and by expenditure type (general practice consultations, medications), cost bearer (PBS, MBS, patient out-of-pocket costs), and broad expenditure category (medication costs, pharmacy costs, general practice consultations, ambulatory blood pressure monitoring)., Results: During 2012-22, estimated total expenditure for the diagnosis and treatment of hypertension in Australia was $12.2 billion: $7.3 billion (60%) was borne by the MBS and PBS, $4.9 billion (40%) by patients as out-of-pocket costs. During 2021-22, an estimated $1.2 billion was spent on the management of hypertension; the three main cost components were pharmacy-related costs (administration and handling fees, dispensing fees, electronic prescription fees: $611.1 million, 50.8%), general practice consultations ($342.7 million, 28.5%), and blood pressure-lowering medications (manufacturer and wholesale costs: $244.3 million, 20.3%)., Conclusions: During 2012-22, about 40% of the cost of managing hypertension in Australia was borne directly by patients (about $494 million per year). Important changes to pharmacy supply and payment policies were introduced in 2023, but further efforts may be needed to reduce treatment costs for patients. These changes are particularly important if the hypertension control rate is to be substantially improved in Australia, given the large numbers of undertreated and untreated people with hypertension., (© 2024 AMPCo Pty Ltd.)

Competing Interests: Conflict of interest: C.L. and D.M. have received institutional NHMRC grant funding for the CARE Network. The authors have no conflicts of interest or financial disclosures to report.

Background: Suicide is the fourth leading cause of death among young people aged 15-29 worldwide. Young people often present to emergency departments (EDs) with self-harm and suicide-related behaviors. The period following discharge from the ED is recognized as one of elevated risk for both repeated self-harm and suicide. During this critical time, suicide prevention aftercare services are recommended. Despite their increased popularity, evidence demonstrating the effectiveness of these models is very limited., Methods: Using a hybrid effectiveness-implementation type I design, this evaluation will assess the effectiveness and implementation of a suicide prevention aftercare (Hospital Outreach Post-suicidal Engagement; HOPE) service designed to reduce risk of self-harm and suicide in young people aged 12-25 who are referred to the service following an ED presentation for self-harm or suicide attempt. Two complementing theoretical frameworks will guide this evaluation, specifically the design, data collection, analysis, and interpretation of results. The RE-AIM evaluation framework will be used to assess Reach, Effectiveness (including cost-effectiveness), Adoption, Implementation and Maintenance of the HOPE aftercare service. The PRISM implementation framework will be used to assess multi-level contextual factors hypothesized to affect the RE-AIM outcomes. Several data sources will be used to assess the changes in primary and secondary outcomes from baseline to post-intervention, and at follow-up, including user and provider self-report surveys, semi-structured interviews, and routinely collected hospital data. An historical control study will also be conducted using data from the Self-Harm Monitoring System for Victoria to examine the impact of the service on rates of self-harm and suicide-related presentations to ED, and compare trends prior to and following commencement of the HOPE aftercare service. In addition, dynamic systems modelling will be used to assess the future scalability of the service., Discussion: Findings from this evaluation will determine the effectiveness, including cost-effectiveness, of the HOPE aftercare service and describe the implementation context. They will inform the future development and sustainability of this and other similar services across Australia and internationally., Trial Registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 19th December 2023 (Registration number ACTRN12623001332617). We do not foresee any amendments to this protocol however, if any unforeseen modifications are required, they will be submitted to ANZCTR., Trial Sponsor: Orygen, 35 Poplar Road, Parkville, VIC, 3052, Australia., Competing Interests: Declarations Ethics approval and consent to participate This project was approved by the Melbourne Health Human Ethics Committee under HREC/81583/MH-2021 and REC/91556/MH-2022. Informed consent to participate will be obtained from all participants in the study. Parental consent will be provided for all participants under the age of 18. Consent for publication Not applicable, as this manuscript does not contain any individual person’ data. Competing interests Several co-authors (DZ, TJ, ML, HR, KW, AC, PM, IZ, AT, CH, MW, EM, BK, JR) are based within the Centre for Youth Mental Health which is the research department of Orygen and part of the University of Melbourne. This is distinct from the clinical services. Clinical staff working in the HOPE aftercare service are funded by Melbourne Health. The authors do not have any financial competing interests to declare., (© 2024. The Author(s).)

Background: Management of type 1 diabetes (T1D) requires the use of insulin, which can cause hypoglycaemia (low blood glucose levels). While most hypoglycaemic episodes can be self-treated, all episodes can be sudden, inconvenient, challenging to prevent or manage, unpleasant and/or cause unwanted attention or embarrassment. Severe hypoglycaemic episodes, requiring assistance from others for recovery, are rare but potentially dangerous. Repeated exposure to hypoglycaemia can reduce classic warning symptoms ('awareness'), thereby increasing risk of severe episodes. Thus, fear of hypoglycaemia is common among adults with T1D and can have a negative impact on how they manage their diabetes, as well as on daily functioning, well-being and quality of life. While advances in glycaemic technologies and group-based psycho-educational programmes can reduce fear, frequency and impact of hypoglycaemia, they are not universally or freely available, nor do they fully resolve problematic hypoglycaemia or associated worries. This study aims to determine the effectiveness of a fully online, self-directed, scalable, psycho-educational intervention for reducing fear of hypoglycaemia: the Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST) programme., Methods: A 24-week, two-arm, parallel-group, hybrid type 1 randomised controlled trial, conducted remotely (online and telephone). Australian adults (≥ 18 years) with self-reported T1D and fear of hypoglycaemia will be recruited, and allocated at random (1:1) to HypoPAST or control (usual care). The primary outcome is the between-group difference in fear of hypoglycaemia (assessed using HFS-II Worry score) at 24 weeks. A sample size of N = 196 is required to detect a 9-point difference, with 90% power and allowing for 30% attrition. Multiple secondary outcomes include self-reported psychological, behavioural, biomedical, health economic, and process evaluation data. Data will be collected at baseline, 12 and 24 weeks using online surveys, 2-week ecological momentary assessments, website analytics and semi-structured interviews., Discussion: This study will provide evidence regarding the effectiveness, cost-effectiveness and acceptability of a novel, online psycho-educational programme: HypoPAST. Due to the fully online format, HypoPAST is expected to provide an inexpensive, convenient, accessible and scalable solution for reducing fear of hypoglycaemia among adults with T1D., Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000894695 (21 August 2023)., (© 2024. The Author(s).)

Background: Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder., Methods: This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted., Discussion: Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022., Protocol Version:  4.14, 26/06/2024., (© 2024. The Author(s).)

Background and Aims: Alcohol use and anxiety often co-occur, causing increased severity impairment. This protocol describes a randomized controlled trial (RCT) that aims to test the efficacy and cost-effectiveness of a web-based, self-guided alcohol and anxiety-focused program, compared with a web-based brief alcohol-focused program, for young adults who drink at hazardous levels and experience anxiety. It will also test moderators and mechanisms of change underlying the intervention effects., Design: This RCT will be conducted with a 1:1 parallel group., Setting: The study will be a web-based trial in Australia., Participants: Individuals aged 17-30 years who drink alcohol at hazardous or greater levels and experience at least mild anxiety (n = 500) will be recruited through social media, media (TV, print) and community networks., Intervention and Comparator: Participants will be randomly allocated to receive a web-based, integrated alcohol-anxiety program plus technical and motivational telephone/e-mail support (intervention) or a web-based brief alcohol-feedback program (control)., Measurements: Clinical measures will be assessed at baseline, post-intervention (2 months), 6 months (primary end-point), 12 months and 18 months. Co-primary outcomes are hazardous alcohol consumption and anxiety symptom severity. Secondary outcomes are binge-drinking frequency; alcohol-related consequences; depression symptoms; clinical diagnoses of alcohol use or anxiety disorder (at 6 months post-intervention), health-care service use, educational and employment outcomes; and quality of life. Mediators and moderators will also be assessed. Efficacy will be tested using mixed models for repeated measures within an intention-to-treat framework. The economic evaluation will analyze individual-level health and societal costs and outcomes of participants between each trial arm, while mediation models will test for mechanisms of change., Comments: This will be the first trial to test whether a developmentally targeted, web-based, integrated alcohol-anxiety intervention is effective in reducing hazardous alcohol use and anxiety severity among young adults. If successful, the integrated alcohol-anxiety program will provide an accessible intervention that can be widely disseminated to improve wellbeing of young adults, at minimal cost., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: We conducted the first non-inferiority, randomised controlled trial to determine whether lifestyle therapy is non-inferior to psychotherapy with respect to mental health outcomes and costs when delivered via online videoconferencing., Methods: An individually randomised, group treatment design with computer-generated block randomisation was used. Between May 2021-April 2022, 182 adults with a Distress Questionnaire-5 score = ≥8 (indicative depression) were recruited from a tertiary mental health service in regional Victoria, Australia and surrounds. Participants were assigned to six 90-min sessions over 8-weeks using group-based, online videoconferencing comprising: (1) lifestyle therapy (targeting nutrition, physical activity) with a dietitian and exercise physiologist (n = 91) or (2) psychotherapy (Cognitive Behavioural Therapy) with psychologists (n = 91). The primary outcome was Patient Health Questionnaire-9 (PHQ-9) depression at 8-weeks (non-inferiority margin ≤2) using Generalised Estimating Equations (GEE). Cost-minimisation analysis estimated the mean difference in total costs from health sector and societal perspectives. Outcomes were assessed by blinded research assistants using Computer Assisted Telephone Interviews. Results are presented per-protocol (PP) and Intention to Treat (ITT) using beta coefficients with 95% Confidence Intervals (CIs)., Findings: The sample was 80% women (mean: 45-years [SD:13.4], mean PHQ-9:10.5 [SD:5.7]. An average 4.2 of 6 sessions were completed, with complete data for n = 132. Over 8-weeks, depression reduced in both arms (PP: Lifestyle (n = 70) mean difference:-3.97, 95% CIs:-5.10, -2.84; and Psychotherapy (n = 62): mean difference:-3.74, 95% CIs:-5.12, -2.37; ITT: Lifestyle (n = 91) mean difference:-4.42, 95% CIs: -4.59, -4.25; Psychotherapy (n = 91) mean difference:-3.82, 95% CIs:-4.05, -3.69) with evidence of non-inferiority (PP GEE β:-0.59; 95% CIs:-1.87, 0.70, n = 132; ITT GEE β:-0.49, 95% CIs:-1.73, 0.75, n = 182). Three serious adverse events were recorded. While lifestyle therapy was delivered at lower cost, there were no differences in total costs (health sector adjusted mean difference: PP AUD$156 [95% CIs -$182, $611, ITT AUD$190 [95% CIs -$155, $651] ]; societal adjusted mean difference: PP AUD$350 [95% CIs:-$222, $1152] ITT AUD$ 408 [95% CIs -$139, $1157]., Interpretation: Remote-delivered lifestyle therapy was non-inferior to psychotherapy with respect to clinical and cost outcomes. If replicated in a fully powered RCT, this approach could increase access to allied health professionals who, with adequate training and guidelines, can deliver mental healthcare at comparable cost to psychologists., Funding: This trial was funded by the Australian Medical Research Future Fund (GA133346) under its Covid-19 Mental Health Research Grant Scheme., Competing Interests: This trial was funded by the National Health and Medical Research Council’s (NHMRC) Medical Research Future Fund–COVID-19 Mental Health Research Australian Government Department of Health (GA133346). AO is supported by a NHMRC Emerging Leader 2 Fellowship (2009295). FNJ is supported by an NHMRC Investigator Grant (#1194982). FNJ has received fellowship funding support from the National Health and Medical Research Council (#1194982) and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Malaysian Society of Gastroenterology and Hepatology, JNPN Congress, American Nutrition Association, Personalised Nutrition Summit, and American Academy of Craniofacial Pain, is a Scientific Advisory Board member of Dauten Family Centre for Bipolar Treatment Innovation (unpaid) and Zoe Nutrition (unpaid), has written two books for commercial publication on the topic of nutritional psychiatry and gut health, and is the principal investigator for the MicroFit Study. She is Director of the Food & Mood Centre, Deakin University, which has received research funding support from Be Fit Food, Bega Dairy and Drinks, and the a2 Milk Company and philanthropic research funding support from the Waterloo Foundation, Wilson Foundation, the JTM Foundation, the Serp Hills Foundation, the Roberts Family Foundation, and the Fernwood Foundation. SR is supported by an NHMRC Investigator Grant (2017506). MB is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131). MTey is supported by a NHMRC Emerging Leadership Fellowship (APP1195335). JS is supported by core funding to the Australian Centre for Behavioural Research in Diabetes provided by the collaboration between Diabetes Victoria and Deakin University. VV is supported by the Rural Health Multidisciplinary Training program. SMah has received funding from Education in Nutrition to provide a professional development presentation and Red Island Olive Oil for social media promotion. MMor has received research grants related to antimicrobial stewardship, discharge medication, consulting fees from Primary Health Networks of Gold Coast and Western Australia related to Primary Sense software. Australian Health Policy Collaboration, RACGP, Australian Department of Health and Aged Care (DoHAC), conference support from RACGP various as chair of Expert Committee for Quality Care, participation in DSMBs for Primary Sense and DoHAC and is a member of Arthritis Australia and Bond University Boards. The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of the funding bodies. The authors have no interests to declare., (© 2024 The Authors.)

Objective: To evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an adjunct to standard care from an Australian health sector perspective, compared to standard care alone for adults with treatment-resistant bipolar depression (TRBD)., Methods: An economic model was developed to estimate the cost per disability-adjusted life-year (DALY) averted and quality-adjusted life-year (QALY) gained for rTMS added to standard care compared to standard care alone, for adults with TRBD. The model simulated the time in three health states (mania, depression, residual) over one year. Response to rTMS was sourced from a meta-analysis, converted to a relative risk and used to modify the time in the depressed state. Uncertainty and sensitivity tested the robustness of results., Results: Base-case incremental cost-effectiveness ratios (ICERs) were $72,299 per DALY averted (95 % Uncertainty Interval (UI): $60,915 to $86,668) and $46,623 per QALY gained (95 % UI: $39,676 - $55,161). At a willingness to pay (WTP) threshold of $96,000 per DALY averted, the base-case had a 100 % probability of being marginally cost-effective. At a WTP threshold of $64,000 per QALY gained, the base-case had a 100 % probability of being cost-effective. Sensitivity analyses decreasing the number of sessions provided, increasing the disability weight or the time spent in the depression state for standard care improved the ICERs for rTMS., Conclusions: Dependent on the outcome measure utilised and assumptions, rTMS would be considered a very cost-effective or marginally cost-effective adjunct to standard care for TRBD compared to standard care alone., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Most people with mental health problems do not seek help, with delays of even decades in seeking professional help. Lack of engagement with professional mental health services can lead to poor outcomes and functional impairment. However, few effective interventions have been identified to improve help-seeking in adults, and those that exist are not widely implemented to deliver public health impact. Co-designing interventions with people with lived experience of mental ill-health and other relevant stakeholders is critical to increase the likelihood of uptake and engagement with these programs., Objective: This study aims to (1) test the effectiveness of a co-designed help-seeking program on increasing professional help-seeking intentions in employees in a workplace setting; (2) determine whether the program reduces mental illness stigma and improves help-seeking intentions and behavior, mental health literacy, mental health symptoms, and work and activity functioning relative to the control condition; (3) explore factors that facilitate broader implementation of the co-designed program; and (4) explore the cost-effectiveness of the co-designed program compared to the control condition over 6 months., Methods: A 2-arm cluster randomized controlled trial will be conducted (target sample: N=900 from 30 to 36 workplaces, with n=25 to 35 participants per workplace). The trial will compare the relative effectiveness of an enhanced interactive program (intervention condition) with a standard psychoeducation-alone program (active control condition) on the primary outcome of professional help-seeking intentions as measured by the General Help-Seeking Questionnaire. Secondary outcomes include the impact on mental illness stigma; mental health literacy; help-seeking attitudes and behavior; work and activity functioning; quality of life; and symptoms of mental ill-health including depression, anxiety, and general psychological distress., Results: Facilitators of and risks to the trial are identified and addressed in this protocol. Recruitment of workplaces is scheduled to commence in the first quarter of 2024., Conclusions: If effective, the program has the potential to be ready for rapid dissemination throughout Australia, with the potential to increase appropriate and efficient service use across the spectrum of evidence-based services., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12623000270617p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385376., International Registered Report Identifier (irrid): PRR1-10.2196/55529., (©Philip J Batterham, Amelia Gulliver, Cassandra Heffernan, Alison L Calear, Aliza Werner-Seidler, Alyna Turner, Louise M Farrer, Mary Lou Chatterton, Cathrine Mihalopoulos, Michael Berk. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.05.2024.)

Objective: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women., Methods: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups., Results: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p  < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p  < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p  < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p  < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p  < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p  < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p  < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p  < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p  < .05) compared to no common mental disorder., Conclusions: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood., Methods: This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment. Adolescents (aged 18-20 years) from the original CSC study who accepted contact at 30-month follow-up and provided informed consent at 60-month follow-up were eligible. The interventions were delivered in school classrooms through an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. Participants took part in two web-based assessments at 60-month and 72-month follow-up. Primary outcomes were alcohol use, cannabis use, anxiety, and depression, measured by self-reported surveys and analysed by intention to treat (ie, in all students who were eligible at baseline). This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785), including the extended follow-up study., Findings: Of 6386 students enrolled from 71 schools, 1556 (24·4%) were randomly assigned to education as usual, 1739 (27·2%) to CSSU, 1594 (25·0%) to CSMH, and 1497 (23·4%) to CSC. 311 (22·2%) of 1401 participants in the control group, 394 (26·4%) of 1495 in the CSSU group, 477 (37·%) of 1289 in the CSMH group, and 400 (32·5%) of 1232 in the CSC group completed follow-up at 72 months. Adolescents in the CSC group reported slower year-by-year increases in weekly alcohol use (odds ratio 0·78 [95% CI 0·66-0·92]; p=0·0028) and heavy episodic drinking (0·69 [0·58-0·81]; p<0·0001) than did the control group. However, significant baseline differences between groups for drinking outcomes, and no difference in the predicted probability of weekly or heavy episodic drinking between groups were observed at 72 months. Sensitivity analyses increased uncertainty around estimates. No significant long-term differences were observed in relation to alcohol use disorder, cannabis use, cannabis use disorder, anxiety, or depression. No adverse events were reported during the trial., Interpretation: We found some evidence that a universal online programme for the prevention of anxiety, depression, and substance use delivered in early adolescence is effective in reducing the use and harmful use of alcohol into early adulthood. However, confidence in these findings is reduced due to baseline differences, and we did not see a difference in the predicted probability of drinking between groups at 72-month follow-up. These findings suggest that a universal prevention programme in adolescence is not sufficient to have lasting effects on mental health and substance use disorders in the long term. In addition to baseline differences, substantial attrition warrants caution in interpretation and the latter factor highlights the need for future long-term follow-up studies to invest in strategies to increase engagement., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MT and NCN are two of the developers of the OurFutures programmes (formerly Climate Schools) and are members of the OurFutures Institute, a not-for-profit charity that distributes the OurFutures programmes to maximise social wellbeing. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Public health guidelines recommend delaying the initiation age for alcohol. However, the causal link between age-at-first-drink (AFD) and future alcohol use in young adulthood is uncertain. This study examined the association between AFD and alcohol-related outcomes at age 20 years using an Australian sample., Methods: Data were obtained from Waves 1-19 (years 2001-2019) of the Household, Income and Labour Dynamics in Australia Survey on 20-year-olds with responses across ≥3 consecutive waves (n = 2278). The AFD for each respondent (between 15 and 20 years) was analysed relative to Australian legal drinking age (18 years). Inverse probability treatment weighting was used to evaluate associations between AFD and four outcomes at age 20 years: risk of current alcohol use; quantity of weekly alcohol consumption; risk of binge drinking; and frequency of binge drinking. Adjustments were made for confounders (e.g., heavy drinking by parents). Robustness of study findings was evaluated using several diagnostic tests/sensitivity analyses., Results: Among 20-year-olds, those with an AFD of 15-16 years consumed significantly more alcohol per week compared to an AFD of 18 years. Additionally, 20-year-old drinkers with an AFD of 16 years were significantly more likely to binge drink (though this association was likely confounded). An inverse dose-response relationship was observed between AFD and weekly alcohol consumption at 20 years, where a higher AFD led to lower alcohol consumption., Conclusion: Study findings indicate an association between a higher AFD and consuming less alcohol in young adulthood, which could potentially support the scale-up of prevention programs to delay AFD among Australian adolescents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Self-reported service use informs resource utilisation and cost estimates, though its validity for use within economic evaluations is uncertain., Objective: The aim of this study is to assess agreement in health resource-use measurement between self-reported and administrative data across different resource categories, over time and between different recall periods by subgroups among Australians living with psychosis., Methods: Data were obtained for 104 participants with psychotic disorders from a randomised controlled trial. Agreement between self-reported resource-use questionnaires and administrative data on community-based services and medication use was assessed through estimating differences of group mean number of visits and medications used and intraclass correlation coefficients (ICC) over multiple time periods., Results: ICC showed moderate agreement across most time periods for general practitioners, psychiatrists and mental health medications. No clear trends were discernible over time, between varying lengths of recall periods nor across participant subgroups., Conclusion: Despite poor agreement, when measuring visits to psychologists and other health professionals, small overall differences in group mean number of visits indicate that self-reported data may still be valid for use in economic evaluations in people living with psychosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato ® ) for depression. However, Spravato is priced at $600-$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public-private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.R., C.G.D., M.L.C., N.G., M.H. and C.L. have all received competitive research grants from NHMRC and MRFF for clinical trials evaluating ketamine in depression. C.L. and M.H. have served on advisory boards for Janssen and C.L. has served on advisory boards for Douglas Pharmaceuticals. NG has received a panel honorarium from Janssen and served on Advisory Boards for Servier and Lundbeck. D.B. is an employee of Psylo. The remaining authors have no conflicts of interest to declare.

Objective: Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies., Methods: A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality., Results: A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%., Conclusion: Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objective: This systematic review updates an existing review examining the cost-effectiveness of interventions to prevent and treat eating disorders (EDs)., Method: Literature search was conducted in Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite, and Health Policy Reference Center electronic databases, capturing studies published between March 2017 to April 2023. Hand-searching was conducted as supplementary including gray literature search. Included articles were (1) full economic evaluations or return-on-investment studies, (2) in English and (3) aimed at prevention and treatment of any ED. Included studies were added and synthesized with previously reviewed studies. Screening and extraction followed PRISMA guidelines. Quality assessment was conducted using the Drummond checklist. PROSPERO registration CRD42021287464., Results: A total of 28 studies were identified, including 15 published after the previous review. There were nine prevention, seven anorexia nervosa (AN) treatment, five bulimia nervosa (BN) treatment, four binge-eating disorder (BED), and three non-specific ED treatment studies. Findings indicate value-for-money evidence supporting all interventions. Quality assessment showed studies were fair-to-good quality., Discussion: There has been significant growth in cost-effectiveness studies over the last 5 years. Findings suggest that interventions to prevent and treat ED offer value for money. Interventions such as Featback (ED prevention and non-specific ED treatment); focal psychodynamic therapy, enhanced cognitive behavioral therapy, and high-calorie refeeding (AN treatment); stepped-care with assisted self-help and internet-based cognitive behavioral therapy (BN treatment); and cognitive behavioral therapy guided self-help intervention (BED treatment) have good quality economic evidence. Further research in implementation of interventions is required., Public Significance Statement: The increasing prevalence of ED globally has significant impact on healthcare systems, families, and society. This review is showcasing the value for money of interventions of eating disorders prevention and treatment. This review found that existing interventions offers positive economic benefit for the healthcare system., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Background: Anorexia nervosa (AN) has amongst the highest mortality rates and the highest treatment costs of any psychiatric disorder. Recently, interest in non-invasive brain stimulation as a novel treatment for AN has grown. These include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)., Methods: This double-blind, randomised sham-controlled trial will compare the relative acceptability and efficacy of tDCS and rTMS in people with AN. 70 participants will be randomised to active or sham tDCS, or active or sham rTMS treatment (2:1:2:1 ratio) over an 8-week treatment period. Participants will receive treatment as usual across the study duration. The primary outcomes are change on the Eating Disorder Examination Questionnaire and treatment acceptability. Secondary outcomes will include change in weight, cognition, mood, interpersonal functioning, and quality of life. Following the 8-week assessment, all participants will have the option of receiving an additional 12 weeks of at-home tDCS. A follow-up assessment will be conducted at 20 weeks post treatment., Discussion: Research into non-invasive brain stimulation as treatments for AN has potential to improve clinical outcomes for patients by comparing the relative efficacy and acceptability of both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS) results from this study will provide important information for informing future larger clinical trials of these treatments for AN., Trial Registration: ClinicalTrials.gov Identifier: NCT05788042., (© 2023. The Author(s).)

Background: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed., Aims: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au., Method: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4., Results: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v . 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v . 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h., Conclusions: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Background: The transdiagnostic effect of continuation/maintenance ECT (CM-ECT) across mood and psychotic disorders on hospital psychiatric readmission risk and total direct cost remains unclear., Methods: A naturalistic retrospective analysis of 540 patients who received inpatient acute ECT treatment from May 2017 to Mar 2021 in a tertiary psychiatric institution. Patients were assessed with validated clinical rating scales pre-ECT and after the first 6 treatments of a course of inpatient acute ECT. After discharge, patients who continued with CM-ECT were compared with those not receiving CM-ECT using survival analysis of hospital readmission. Total direct cost (hospitalisation and ECT treatment cost) was also analysed. All patients were subjected to a standard post-discharge monitoring program with case managers checking in on the patients regularly after discharge and ensuring they were given an outpatient appointment within a month of discharge., Results: Both cohorts had significant improvement in their rating scales scores after their first six 6 sessions of inpatient acute ECT. Patients who continued with CM-ECT after completing their inpatient acute ECT (mean number of acute ECT: N = 9.9, SD 5.3), had a significantly lower risk of readmission [adjusted hazard ratio of 0.68 (95 % CI: 0.49-0.94, p = 0.020)]. Patients who received CM-ECT also had a significantly lower average total direct cost compared to those who did not (SGD$35,259 vs SGD$61,337). For patients with mood disorders, the CM-ECT group had a significantly lower inpatient ECT cost, hospitalisation cost and total direct costs compared to those without CM-ECT., Limitations: The naturalistic study cannot prove a causal relationship between CM-ECT and reduced readmission and lower healthcare costs., Conclusion: CM-ECT is associated with lower readmission risks and lower total direct healthcare costs for the treatment of mood and psychotic disorders, especially for mood disorders., Competing Interests: Declaration of competing interest We confirm that the content of this manuscript is original research and has not been previously published, nor is it currently being submitted for publication elsewhere. There is no funding source for this study. We have no conflict of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Substance use disorders negatively affect global disease burden. Effective preventive interventions are available, but whether they provide value for money is unclear., Aims: This review looks at the cost-effectiveness evidence of preventive interventions for cannabis use, opioid misuse and illicit drug use., Method: Literature search was undertaken in Medline, CINAHL, PsycINFO, EconLit through EBSCOhost and EMBASE, up to May 2021. Grey literature search was conducted as supplement. Studies included were full economic evaluations or return-on-investment (ROI) analyses for preventing opioid misuse, cannabis and illicit drug use. English-language restriction was used. Outcomes extracted were incremental cost-effectiveness ratios (ICER) or ROI ratios, with costs presented in 2019 United States dollars. Quality was assessed with the Drummond checklist., Results: Eleven full economic evaluation studies were identified from 5674 citations, with all studies conducted in high-income countries. Most aimed to prevent opioid misuse ( n = 4), cannabis ( n = 3) or illicit drug use ( n = 5). Modelling was the predominant methodology ( n = 7). Five evaluated school-based universal interventions targeting children and adolescents (aged <18 years). Five cost-benefit studies reported cost-savings. One cost-effectiveness and two cost-utility analysis studies supported the cost-effectiveness of interventions, as ICERs fell under prespecified value-for-money thresholds., Conclusions: There are limited economic evaluations of preventive interventions for opioid misuse, cannabis and illicit drug use. Family-based intervention (ParentCorps), school-based interventions (Social and Emotional Training and Project ALERT) and a doctor's programme to assess patient risk of misusing narcotics ('the Network System to Prevent Doctor-Shopping for Narcotics') show promising cost-effectiveness and warrant consideration.

Background: Alcohol use is a leading risk factor for death and disability worldwide., Aims: We conducted a systematic review on the cost-effectiveness evidence for interventions to prevent alcohol use across the lifespan., Method: Electronic databases (EMBASE, Medline, PsycINFO, CINAHL and EconLit) were searched for full economic evaluations and return-on-investment studies of alcohol prevention interventions published up to May 2021. The methods and results of included studies were evaluated with narrative synthesis, and study quality was assessed by the Drummond ten-point checklist., Results: A total of 69 studies met the inclusion criteria for a full economic evaluation or return-on-investment study. Most studies targeted adults or a combination of age groups, seven studies comprised children/adolescents and one involved older adults. Half of the studies found that alcohol prevention interventions are cost-saving (i.e. more effective and less costly than the comparator). This was especially true for universal prevention interventions designed to restrict exposure to alcohol through taxation or advertising bans; and selective/indicated prevention interventions, which involve screening with or without brief intervention for at-risk adults. School-based interventions combined with parent/carer interventions were cost-effective in preventing alcohol use among those aged under 18 years. No interventions were cost-effective for preventing alcohol use in older adults., Conclusions: Alcohol prevention interventions show promising evidence of cost-effectiveness. Further economic analyses are needed to facilitate policy-making in low- and middle-income countries, and among child, adolescent and older adult populations.

Objective: Investigate the economic consequences of injuries to female Australian footballers from a health sector and societal perspective., Methods: This prospective observational study invited 242 females to complete an online questionnaire 3-6 months following an Australian football injury which involved presentation to an ED in Victoria, Australia. The questionnaire inquired regarding healthcare use, time off work, return to playing football and extent of recovery following injury. Relevant information was also extracted from respondents' medical records regarding injury-type, body part injured, investigations and treatments. Healthcare costs were determined for each respondent's ED presentation, hospital admission/s (when relevant), and subsequent healthcare use. Societal costs were determined as lost income to the respondent and/or carer., Results: A total of 108 people responded to the questionnaire. Sprains/strains and fractures accounted for 84.2% of respondents' injuries. Sixteen respondents (14.8%) required admission to hospital at the time of injury and 81 (75.0%) required subsequent healthcare appointments following discharge from the ED or hospital. Time off work or school following the injury was common (64.8% of respondents) and 27.8% of respondents had a carer take time off work. More than 80% of respondents missed training and matches following the injury. The median healthcare cost per respondent was AUD$753 and the median cost due to work absence was AUD$1393. One-quarter of respondents reported a full recovery., Conclusions: Injuries to female Australian footballers can produce substantial healthcare and societal costs, which has important implications for healthcare provision and prioritising and implementing injury prevention programmes and post-injury rehabilitation., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Background: Mental health problems are common among people with diabetes. However, evidence-based strategies for the prevention and early intervention of emotional problems in people with diabetes are lacking. Our aim is to assess the real-world effectiveness, cost-effectiveness, and implementation of a Low-Intensity mental health Support via a Telehealth Enabled Network (LISTEN), facilitated by diabetes health professionals (HPs)., Methods: A hybrid type I effectiveness-implementation trial, including a two-arm parallel randomised controlled trial, alongside mixed methods process evaluation. Recruited primarily via the National Diabetes Services Scheme, Australian adults with diabetes (N = 454) will be eligible if they are experiencing elevated diabetes distress. Participants are randomised (1:1 ratio) to LISTEN-a brief, low-intensity mental health support program based on a problem-solving therapy framework and delivered via telehealth (intervention) or usual care (web-based resources about diabetes and emotional health). Data are collected via online assessments at baseline (T0), 8 weeks (T1) and 6 months (T2, primary endpoint) follow-up. The primary outcome is between-group differences in diabetes distress at T2. Secondary outcomes include the immediate (T1) and longer-term (T2) effect of the intervention on psychological distress, general emotional well-being, and coping self-efficacy. A within-trial economic evaluation will be conducted. Implementation outcomes will be assessed using mixed methods, according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Data collection will include qualitative interviews and field notes., Discussion: It is anticipated that LISTEN will reduce diabetes distress among adults with diabetes. The pragmatic trial results will determine whether LISTEN is effective, cost-effective, and should be implemented at scale. Qualitative findings will be used to refine the intervention and implementation strategies as required., Trial Registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622000168752) on 1 February, 2022., (© 2023. The Author(s).)

Background: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs., Methods: The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18-65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention., Discussion: This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care., Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021., (© 2023. The Author(s).)

Objectives: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD., Methods: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial ( n = 15) of enema-delivered FMT ( n = 10) compared with a placebo enema ( n = 5) in adults with moderate-to-severe MDD., Results: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD., Conclusions: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

The objectives of this study are to assess the association between childhood bullying and preference-based health-related quality of life (QoL) in Australian school children and their parents and estimate quality-adjusted life years (QALYs) associated with bullying chronicity. Children aged 8-10 years completed the child health utilities (CHU-9D), while parents completed the Australian quality of life (AQoL-8D). Children were grouped into four categories of bullying involvement (no bullying, victim, perpetrator, or both perpetrator and victim) based on the Revised Olweus Bully/Victim Questionnaire. Parental data were compared across two bullying involvement groups (bullying vs. no bullying). QALYs were calculated for children over two years and comparisons made based on the number of assessments where bullying was reported (baseline, 1- and 2-year follow up). Children who were involved in bullying (victims and/or perpetrators) reported statistically significantly lower mean utility scores compared to children who were not involved in bullying. Parents whose child was involved in bullying had significantly lower mean utility scores compared to parents of children not involved with bullying. There appeared to be a dose-response relationship, with higher QALY losses associated with increasing frequency of reported bullying. Bullying among Australian school children was associated with significantly lower preference-based QoL for themselves and their parents. This study also confirmed the significant burden of disease for bullying among children measured by an incremental decrease in QALY with an increasing chronicity of bullying over time., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Stepped-care is a commonly recommended and implemented care model across health care domains, including substance use. Despite their presumed efficient allocation of treatment resources, a current and robust evidence synthesis is needed on the efficacy, effectiveness and cost-effectiveness of stepped-care for substance use., Methods: This systematic review analyzed articles describing evaluations of stepped-care models that measured the use of acutely psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in participants over 18 years old. The analysis investigated model and participant characteristics associated with treatment outcomes., Results: The study team conducted a search of five databases of literature (PsychINFO, MEDLINE, Embase, Cochrane Library and Scopus) published between January 1, 2010, and November 1, 2020. The search yielded 1051 unique articles, 19 of which were included in the analysis. The studies had considerable variability in sample sizes (n = 18-2310), time to follow-up (4.5 months to 3 years), and retention rates (35.1-100 %). Studies examined outcomes for either alcohol alone (n = 9), alcohol and other drug use (n = 9), or drug use alone (n = 1). Most studies (n = 13;) were rated as good quality. Three (15.8 %) were rated as fair and three (15.8 %) were rated as poor quality. The evidence regarding the efficacy, effectiveness and cost-effectiveness of stepped-care approaches is limited, but four of seven studies found that adaptive-care interventions delivered in the context of other systemic interventions produced greater benefit than control conditions in relation to at least one alcohol-related outcome. We have insufficient evidence to determine whether the modes or intensity of interventions included in the models, or decision rules used to step people up or down to differing levels of care, have an impact on outcome., Conclusion: Heterogeneity between studies with regard to model and evaluation design limited the degree to which the analysis could draw robust conclusions. Sample recruitment and statistical power are particular challenges, and the field needs more innovative evaluation designs to assess the efficacy, effectiveness, and cost-effectiveness of stepped-care models., Competing Interests: Declaration of competing interest The authors declare no financial or non-financial competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Employee alcohol and other drug use can negatively impact the workplace, resulting in absenteeism, reduced productivity, high turnover, and worksite safety issues. As the workplace can influence employee substance use through environmental and cultural factors, it also presents a key opportunity to deliver interventions, particularly to employees who may not otherwise seek help. This is a systematic review of workplace-based interventions for the prevention and treatment of problematic substance use. Five databases were searched for efficacy, effectiveness and/or cost-effectiveness studies and reviews published since 2010 that measured use of psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in employees aged over 18. Thirty-nine articles were identified, 28 describing primary research and 11 reviews, most of which focused solely on alcohol use. Heterogeneity between studies with respect to intervention and evaluation design limited the degree to which findings could be synthesized, however, there is some promising evidence for workplace-based universal health promotion interventions, targeted brief interventions, and universal substance use screening. The few studies that examined implementation in the workplace revealed specific barriers including lack of engagement with e-health interventions, heavy use and reluctance to seek help amongst male employees, and confidentiality concerns. Tailoring interventions to each workplace, and ease of implementation and employee engagement emerged as facilitators. Further high-quality research is needed to examine the effectiveness of workplace substance use testing, Employee Assistance Programs, and strategies targeting the use of substances other than alcohol in the workplace., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=227598, PROSPERO [CRD42021227598]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morse, Askovic, Sercombe, Dean, Fisher, Marel, Chatterton, Kay-Lambkin, Barrett, Sunderland, Harvey, Peach, Teesson and Mills.)

Background: Internet-delivered psychosocial interventions can overcome barriers to face-to-face psychosocial care, but limited evidence supports their cost-effectiveness for people with bipolar disorders (BDs)., Objective: This study aimed to conduct within-trial cost-effectiveness and cost-utility analyses of an internet-based intervention for people with BD, MoodSwings 2.0, from an Australian health sector perspective., Methods: MoodSwings 2.0 included an economic evaluation alongside an international, parallel, and individually stratified randomized controlled trial comparing an internet-based discussion forum (control; group 1), a discussion forum plus internet-based psychoeducation (group 2), and a discussion forum plus psychoeducation and cognitive behavioral tools (group 3). The trial enrolled adults (aged 21 to 65 years) with a diagnosis of BD assessed by telephone using a structured clinical interview. Health sector costs included intervention delivery and additional health care resources used by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS; the trial primary outcome) and quality-adjusted life years (QALYs) calculated using the short-form 6-dimension instrument derived from the 12-item version of the short-form health survey. Average incremental cost-effectiveness (cost per MADRS score) and cost-utility (cost per QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed effects models in the base case., Results: In total, 304 participants were randomized. Average health sector cost was lowest for group 2 (Aus $9431, SD Aus $8540; Aus $1=US $0.7058) compared with the control group (Aus $15,175, SD Aus $17,206) and group 3 (Aus $15,518, SD Aus $30,523), but none was statistically significantly different. The average QALYs were not significantly different among the groups (group 1: 0.627, SD 0.062; group 2: 0.618, SD 0.094; and group 3: 0.622, SD 0.087). The MADRS scores were previously shown to differ significantly between group 2 and the control group at all follow-up time points (P<.05). Group 2 was dominant (lower costs and greater effects) compared with the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI dominated to Aus $331). Average cost per point change in MADRS score for group 3 versus the control group was dominant (95% CI dominant to Aus $22,585). Group 2 was dominant (95% CI Aus $43,000 to dominant) over the control group based on lower average health sector cost and average QALY benefit of 0.012 (95% CI -0.009 to 0.033). Group 3, compared with the control group, had an average incremental cost-effectiveness ratio of dominant (95% CI dominated to Aus $19,978)., Conclusions: Web-based psychoeducation through MoodSwings 2.0 has the potential to be a cost-effective intervention for people with BD. Additional research is needed to understand the lack of effectiveness for the addition of cognitive behavioral tools with the group 3 intervention., (©Mary Lou Chatterton, Yong Yi Lee, Lesley Berk, Mohammadreza Mohebbi, Michael Berk, Trisha Suppes, Sue Lauder, Cathrine Mihalopoulos. Originally published in JMIR Mental Health (https://mental.jmir.org), 01.11.2022.)

Background: This paper reports on the cost-effectiveness evaluation of Link-me - a digitally supported, systematic approach to triaging care for depression and anxiety in primary care that uses a patient-completed Decision Support Tool (DST)., Methods: The economic evaluation was conducted alongside a parallel, stratified individually randomised controlled trial (RCT) comparing prognosis-matched care to usual care at six- and 12-month follow-up. Twenty-three general practices in three Australian Primary Health Networks recruited 1,671 adults (aged 18 - 75 years), predicted by the DST to have minimal/mild or severe depressive or anxiety symptoms in three months. The minimal/mild prognostic group was referred to low intensity services. Participants screened in the severe prognostic group were offered high intensity care navigation, a model of care coordination. The outcome measures included in this evaluation were health sector costs (including development and delivery of the DST, care navigation and other healthcare services used) and societal costs (health sector costs plus lost productivity), psychological distress [Kessler Psychological Distress Scale (K10)] and quality adjusted life years (QALYs) derived from the EuroQol 5-dimension quality of life questionnaire with Australian general population preference weights applied. Costs were valued in 2018-19 Australian dollars (A$)., Results: Across all participants, the health sector incremental cost-effectiveness ratio (ICER) of Link-me per point decrease in K10 at six months was estimated at $1,082 (95% CI $391 to $6,204) increasing to $2,371 (95% CI $191 to Dominated) at 12 months. From a societal perspective, the ICER was estimated at $1,257/K10 point decrease (95% CI Dominant to Dominated) at six months, decreasing to $1,217 (95% CI Dominant to Dominated) at 12 months. No significant differences in QALYs were detected between trial arms and the intervention was dominated (less effective, more costly) based on the cost/QALY ICER., Conclusions: The Link-me approach to stepped mental health care would not be considered cost-effective utilising a cost/QALY outcome metric commonly adopted by health technology assessment agencies. Rather, Link-me showed a trend toward cost-effectiveness by providing improvement in mental health symptoms, measured by the K10, at an additional cost., Trial Registration: Australian and New Zealand Clinical Trials Registry, ANZCTRN 12617001333303., (© 2022. The Author(s).)

Background: COVID-19 required mental health services to quickly switch from face-to-face service delivery to telehealth (telephone and videoconferencing). This evaluation explored implementation of a telehealth mental health response in a regional public mental health provider., Methods: A mixed methods approach, combining service use data, brief satisfaction surveys, and qualitative interviews/focus groups was undertaken. Number and types of contacts from de-identified mental health service data were compared between April-May 2020 and April-May 2019. Mental health consumers and providers completed brief online satisfaction surveys after videoconferencing sessions. Attitudes and perspectives on the implementation of telehealth were further explored by applying a descriptive qualitative framework to the analysis of interview and focus group data supplied by consumers and providers. Template thematic analysis was used to elucidate key themes relating to the barriers and enablers of telehealth uptake and future implementation recommendations., Results: Total contacts decreased by 13% from 2019 to 2020. Face-to-face contacts decreased from 55% of total in 2019 to 24% in 2020. In 2019, 45% of contacts were by telephone, increasing to 70% in 2020. Only four videoconferencing contacts were made in 2019; increasing to 886 in 2020. Consumer surveys (n = 26) rated videoconferencing as good or excellent for technical quality (92%), overall experience (86%), and satisfaction with personal comfort (82%). Provider surveys (n = 88) rated technical quality as good or excellent (68%) and 86% could achieve assessment/treatment goals with videoconferencing. Provider focus groups/interviews (n = 32) identified that videoconferencing was well-suited to some clinical tasks. Consumers interviewed (n = 6) endorsed the ongoing availability of telehealth within a blended approach to service delivery. Both groups reflected on videoconferencing limitations due to infrastructure (laptops, phones, internet access), cumbersome platform and privacy concerns, with many reverting to telephone use., Conclusions: While videoconferencing increased, technical and other issues led to telephone being the preferred contact method. Satisfaction surveys indicated improvement opportunities in videoconferencing. Investment in user-friendly platforms, telehealth infrastructure and organisational guidelines are needed for successful integration of videoconferencing in public mental health systems., (© 2022. The Author(s).)

Background: Target-D, a new person-centred e-health platform matching depression care to symptom severity prognosis (minimal/mild, moderate or severe) has demonstrated greater improvement in depressive symptoms than usual care plus attention control. The aim of this study was to evaluate the cost-effectiveness of Target-D compared to usual care from a health sector and partial societal perspective across 3-month and 12-month follow-up., Methods and Findings: A cost-utility analysis was conducted alongside the Target-D randomised controlled trial; which involved 1,868 participants attending 14 general practices in metropolitan Melbourne, Australia. Data on costs were collected using a resource use questionnaire administered concurrently with all other outcome measures at baseline, 3-month and 12-month follow-up. Intervention costs were assessed using financial records compiled during the trial. All costs were expressed in Australian dollars (A$) for the 2018-19 financial year. QALY outcomes were derived using the Assessment of Quality of Life-8D (AQoL-8D) questionnaire. On a per person basis, the Target-D intervention cost between $14 (minimal/mild prognostic group) and $676 (severe group). Health sector and societal costs were not significantly different between trial arms at both 3 and 12 months. Relative to a A$50,000 per QALY willingness-to-pay threshold, the probability of Target-D being cost-effective under a health sector perspective was 81% at 3 months and 96% at 12 months. From a societal perspective, the probability of cost-effectiveness was 30% at 3 months and 80% at 12 months., Conclusions: Target-D is likely to represent good value for money for health care decision makers. Further evaluation of QALY outcomes should accompany any routine roll-out to assess comparability of results to those observed in the trial. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000537459)., Competing Interests: The authors have declared that no competing interests exist.

Background: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a 'first-line', 'non-negotiable' treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks., Methods: The study is being conducted in partnership with Barwon Health's Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance., Discussion: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820 , Registered 8 April 2021., (© 2022. The Author(s).)

Objective: To identify and describe the available literature quantifying the economic burden associated with the negative symptoms of schizophrenia., Methods: A search of five electronic databases (Medline, PsycINFO, EconLit, CINAHL, EMBASE) and hand searches of bibliographies was conducted to identify all relevant articles written in English and published from date of database inception to January 2021. Search strategies included terms for schizophrenia, negative symptoms, direct and indirect costs and health-care resource utilisation. Quality assessment of included articles was undertaken using a standardised checklist for the evaluation of cost of illness studies. Annual costs were converted to 2022 Australian dollars (A$)., Results: Four hundred and thirty-six abstracts were identified for inclusion. Following screening, six unique studies utilizing data from 6293 participants with an average age of 40 were identified to inform the review. Study quality was high for four studies. All studies concluded there was a positive relationship between negative symptoms and costs or resource utilisation. Four studies providing cost data show an increase in direct costs per annum associated with negative symptoms (range A$ 4046 to 171,564). The wide range in costs was attributable to between study differences in patient characteristics and cohorts, included costs, and country of study., Conclusion: Health care costs and resource utilisation are associated with negative symptoms in people with schizophrenia. Heterogeneity prevented calculation of an overall dollar value per point increase in negative symptoms. Future research is warranted to further quantify the relationship between negative symptoms and costs, including health sector and societal., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The early postnatal period is a time of increased risk for psychiatric admission. However, there is scope to further examine if this increase in risk extends to the entire perinatal period (pregnancy and first postnatal year), and how it compares to admission outside of the perinatal period., Methods: Data were linked across birth and hospital admission registers from July 2000 to December 2009. The study cohort, consisting of all pregnant and childbearing women with a psychiatric history, was divided into two groups: case women (at least one perinatal principal psychiatric admission in the study period) (38%) and comparison women (no perinatal principal psychiatric admissions) (62%). Outcomes were admission rate and length of stay adjusted for diagnosis, socio-demographic factors and timing of admission., Results: Antenatal and postnatal admissions rates were both higher than non-perinatal admission rates for case women for all diagnoses. There was little evidence that women with perinatal admissions were at an increased risk of admissions at other times. Socially disadvantaged women had significantly fewer and shorter admissions than their respective counterparts., Conclusions: The entire perinatal period is a time of increased risk for admission across the range of psychiatric disorders, compared to other times in a woman's childbearing years. Reduced admission rate and length of stay for socially disadvantaged women suggest lack of equity of access highlighting the importance of national perinatal mental health policy initiatives inclusive of disadvantaged groups., (© 2021. Crown.)