Age at first drink and its influence on alcohol use behaviours in young adulthood: Evidence from an Australian household-based panel study.

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.

Economic evidence for prevention and treatment of eating disorders: An updated systematic review.

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.

OBJETIVO: Esta revisión sistemática actualiza una revisión existente que examina la rentabilidad de las intervenciones para prevenir y tratar los trastornos de la conducta alimentaria (TCA). MÉTODO: Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite y Health Policy Reference Center, abarcando estudios publicados entre marzo de 2017 y abril de 2023. Se realizó una búsqueda manual como complemento, incluyendo la búsqueda de literatura gris. Los artículos incluidos eran (1) evaluaciones económicas completas o estudios de retorno de inversión, (2) en inglés y (3) dirigidos a la prevención y tratamiento de cualquier TCA. Los estudios incluidos se añadieron y sintetizaron con estudios previamente revisados. El cribado y la extracción siguieron las pautas PRISMA. La evaluación de la calidad se realizó utilizando la lista de verificación de Drummond. Registro en PROSPERO CRD42021287464. RESULTADOS: Se identificaron 28 estudios, incluyendo 15 publicados después de la revisión anterior. Hubo nueve estudios de prevención, siete de tratamiento de anorexia nerviosa (AN), cinco de tratamiento de bulimia nerviosa (BN), cuatro de trastorno por atracón (TpA) y tres de tratamiento de TCA no especificados. Los hallazgos indican evidencia de valor por dinero que respalda todas las intervenciones. La evaluación de la calidad mostró que los estudios eran de calidad aceptable a buena. DISCUSIÓN: Ha habido un crecimiento significativo en los estudios de rentabilidad en los últimos cinco años. Los hallazgos sugieren que las intervenciones para prevenir y tratar los TCA ofrecen valor por dinero. Intervenciones como Featback (prevención de TCA y tratamiento de TCA no específicos); terapia psicodinámica focal, terapia cognitivo-conductual mejorada y rehabilitación nutricional con alto contenido calórico (tratamiento de AN); atención escalonada con autoayuda asistida y terapia cognitivo-conductual en línea (tratamiento de BN); y terapia cognitivo-conductual guiada de autoayuda (tratamiento de TpA) tienen una buena evidencia económica de calidad. Se requiere más investigación en la implementación de intervenciones.

Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia.

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.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

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.

Cost-utility analysis of adjunct repetitive transcranial magnetic stimulation for treatment resistant bipolar depression.

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.

A Brief Workplace Training Program to Support Help-Seeking for Mental Ill-Health: Protocol for the Helipad Cluster Randomized Controlled Trial.

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.

Web-based intervention for young adults experiencing anxiety and hazardous alcohol use: Study protocol for an 18-month randomized controlled trial.

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.

Effectiveness of a universal, school-based, online programme for the prevention of anxiety, depression, and substance misuse among adolescents in Australia: 72-month outcomes from a cluster-randomised controlled trial.

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.

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

Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.