BACKGROUND:Depression in both bipolar and major depressive disorder remains a major unmet need due to treatment resistance to the existing treatments. Emerging evidence implicates the renin-angiotensin system in regulating the cellular stress response relevant to depression, suggesting it as a novel therapeutic target for depression. Candesartan, a common hypertension medication, decreases neuroinflammation, oxidative and nitrosative pathway activation, and neurotrophic signalling of angiotensin II by predominantly blocking the angiotensin II type 1 receptors (AT1R). Given AT1R-induced activities are implicated in the pathophysiology of bipolar and major depressive disorder and with supportive pharmacoepidemiology data, candesartan may represent a novel antidepressant strategy. METHODS:The CADET Trials are 2 parallel 16-week double-blind randomized placebo-controlled trials of adjunctive candesartan (or placebo) for the treatment of bipolar depression (CADET-BD) and major depressive disorder (CADET-UD). Each trial aims to recruit 240 adult participants. The primary outcome is the between-group (ie, intervention vs. placebo) differential change from baseline to week 16 in depression symptoms as measured by the Montgomery Åsberg Depression Rating Scale. Secondary outcomes measure depression, mania, anxiety, quality of life, cost-effectiveness, functioning, substance use, cognition, and biological markers. FINDINGS:Findings are not yet available as the trial is ongoing. IMPLICATIONS:The CADET Trials examine the efficacy of candesartan in reducing depressive symptoms in both unipolar and bipolar depression, and whether its effects are mediated through the renin-angiotensin system. Candesartan is affordable, accessible, and well-tolerated. If effective, it could quickly be adopted into clinical practice as a new adjunctive medication for the treatment of these disorders.

Importance:Methamphetamine use disorder is a global health challenge for which there are no approved pharmacotherapies. The safety and effectiveness of mirtazapine, a promising candidate for methamphetamine use disorder, has not been established in routine clinical practice. Objective:To determine the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder in routine clinical practice. Design, Setting, and Participants:This phase 3, parallel-group, double-blind, placebo-controlled randomized clinical trial was conducted between November 16, 2022, and May 1, 2025, at 6 outpatient alcohol and other drug clinics in Australia among adults with moderate to severe methamphetamine use disorder. Data analysis was conducted from May to September 2025. Intervention:Mirtazapine (30 mg daily for 12 weeks) or equivalent placebo. Main Outcomes and Measures:The primary end point was the change in days of methamphetamine use in the past 28 days from baseline to week 12. Secondary end points were depression, insomnia, HIV risk behavior, quality of life, and methamphetamine-negative oral fluid samples. Results:Of 344 participants randomized, 339 participants received the intervention (167 in the placebo group and 172 in the mirtazapine group). Mean (SD) age was 42.0 (8.6) years, 126 participants (37.2%) were female, and participants had used methamphetamine for a median (IQR) of 24 days (17-28) of the past 28 days at baseline. The mean reduction in days of methamphetamine use from baseline to week 12 was greater in the mirtazapine group (7.0 days of 28 days) than in the placebo group (4.8 days of 28 days; mean difference, 2.2 days; 95% CI, -4.2 to -0.2 days; P = .02). More participants in the mirtazapine group reported drowsiness (47% vs 33%) and weight gain (10% vs 3%). Forty participants (23%) discontinued mirtazapine due to adverse events compared to 25 participants (15%) in the placebo group. No significant effects of mirtazapine on secondary end points were found. Conclusions and Relevance:In this parallel-group randomized clinical trial, mirtazapine delivered in routine clinical practice reduced methamphetamine use in adults with methamphetamine use disorder. No unexpected safety concerns delivering mirtazapine in this setting were found; this finding has important clinical implications in the absence of any approved pharmacotherapies for methamphetamine use disorder. Trial Registration:anzctr.org.au Identifier: ACTRN12622000235707.

Background:Depression in both bipolar and major depressive disorder remains a major unmet need due to treatment resistance to the existing treatments. Emerging evidence implicates the renin-angiotensin system in regulating the cellular stress response relevant to depression, suggesting it as a novel therapeutic target for depression. Candesartan, a common hypertension medication, decreases neuroinflammation, oxidative and nitrosative pathway activation, and neurotrophic signalling of angiotensin II by predominantly blocking the angiotensin II type 1 receptors (AT1R). Given AT1R-induced activities are implicated in the pathophysiology of bipolar and major depressive disorder and with supportive pharmacoepidemiology data, candesartan may represent a novel antidepressant strategy.MethodsThe CADET Trials are 2 parallel 16-week double-blind randomized placebo-controlled trials of adjunctive candesartan (or placebo) for the treatment of bipolar depression (CADET-BD) and major depressive disorder (CADET-UD). Each trial aims to recruit 240 adult participants. The primary outcome is the between-group (ie, intervention vs. placebo) differential change from baseline to week 16 in depression symptoms as measured by the Montgomery & Aring;sberg Depression Rating Scale. Secondary outcomes measure depression, mania, anxiety, quality of life, cost-effectiveness, functioning, substance use, cognition, and biological markers.Findings:Findings are not yet available as the trial is ongoing.Implications:The CADET Trials examine the efficacy of candesartan in reducing depressive symptoms in both unipolar and bipolar depression, and whether its effects are mediated through the renin-angiotensin system. Candesartan is affordable, accessible, and well-tolerated. If effective, it could quickly be adopted into clinical practice as a new adjunctive medication for the treatment of these disorders.

Background:Programs to support mental health in workplaces, particularly those using digital methods, show promise for increasing appropriate use of services. However, it is unclear which factors influence the successful implementation of such programs. Methods:Implementation outcomes from a cluster randomised trial (cRCT) of a digital single-session intervention (Helipad program) for improving mental health help seeking in employees were explored using both qualitative interviews (n = 16) and quantitative data collected at post-test during the cRCT (N = 344). Linear regression analyses tested predictors of participation (uptake) by workplace, and predictors of participant views about the acceptability, appropriateness, and feasibility of both the Helipad program and the control (static psychoeducation only). Qualitative data were thematically analysed to summarise feedback and recommendations around implementing the program, based on the Consolidated Framework for Implementation Research. Results:The Helipad program performed better than the control program for participant implementation outcomes, with significantly superior acceptability, appropriateness, and feasibility. More intensive methods to encourage participation such as additional emails, meetings, and delivery via a learning management system were associated with significantly greater uptake. There were few differences in acceptability ratings between workplace types indicating that the program may be useful and acceptable in a broad range of settings. Qualitative data indicated that the Helipad program was easy-to-use and contained a broad range of information on workplace mental health. A challenge identified by participants was how to best engage people with less interest or low perceived need for mental health support. Recommendations for implementation included ensuring workplace leader investment, allowing time during work to complete the program and modelling positive attitudes and behaviours towards mental health and help seeking. Conclusions:Implementation of workplace mental health interventions can be enhanced by clear communication with workplace leaders about its benefits, and by facilitating engagement of employees with the program during work time. Partnerships with stakeholders such as insurance companies or industry bodies may improve reach.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12623000270617.

QuestionIs mirtazapine safe and effective for methamphetamine use disorder when delivered in routine clinical practice?FindingsIn this double-blind, placebo-controlled randomized clinical trial of 344 adults with methamphetamine use disorder, 12 weeks of mirtazapine (30 mg/day) delivered in routine clinical practice produced a greater reduction in methamphetamine use days than placebo. There were no unexpected safety concerns from mirtazapine.MeaningMirtazapine is safe and effective when used in routine clinical practice for reducing methamphetamine use in adults with methamphetamine use disorder. ImportanceMethamphetamine use disorder is a global health challenge for which there are no approved pharmacotherapies. The safety and effectiveness of mirtazapine, a promising candidate for methamphetamine use disorder, has not been established in routine clinical practice.ObjectiveTo determine the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder in routine clinical practice.Design, Setting, and ParticipantsThis phase 3, parallel-group, double-blind, placebo-controlled randomized clinical trial was conducted between November 16, 2022, and May 1, 2025, at 6 outpatient alcohol and other drug clinics in Australia among adults with moderate to severe methamphetamine use disorder. Data analysis was conducted from May to September 2025.InterventionMirtazapine (30 mg daily for 12 weeks) or equivalent placebo.Main Outcomes and MeasuresThe primary end point was the change in days of methamphetamine use in the past 28 days from baseline to week 12. Secondary end points were depression, insomnia, HIV risk behavior, quality of life, and methamphetamine-negative oral fluid samples.ResultsOf 344 participants randomized, 339 participants received the intervention (167 in the placebo group and 172 in the mirtazapine group). Mean (SD) age was 42.0 (8.6) years, 126 participants (37.2%) were female, and participants had used methamphetamine for a median (IQR) of 24 days (17-28) of the past 28 days at baseline. The mean reduction in days of methamphetamine use from baseline to week 12 was greater in the mirtazapine group (7.0 days of 28 days) than in the placebo group (4.8 days of 28 days; mean difference, 2.2 days; 95% CI, -4.2 to -0.2 days; P = .02). More participants in the mirtazapine group reported drowsiness (47% vs 33%) and weight gain (10% vs 3%). Forty participants (23%) discontinued mirtazapine due to adverse events compared to 25 participants (15%) in the placebo group. No significant effects of mirtazapine on secondary end points were found.Conclusions and RelevanceIn this parallel-group randomized clinical trial, mirtazapine delivered in routine clinical practice reduced methamphetamine use in adults with methamphetamine use disorder. No unexpected safety concerns delivering mirtazapine in this setting were found; this finding has important clinical implications in the absence of any approved pharmacotherapies for methamphetamine use disorder.Trial Registrationanzctr.org.au Identifier: ACTRN12622000235707 This randomized clinical trial conducted in Australia determines the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder in routine clinical practice.

Bipolar disorder is dominated by the depressive phase, and its treatment represents the greatest unmet need in mood disorders. Converging evidence indicates that bipolar depression is characterized by reduced mitochondrial function compared to the euthymic phase, with the severity of depressive symptoms correlated with the extent of mitochondrial dysfunction. Trimetazidine, a medication for angina pectoris, improves efficiency of mitochondrial energy generation and reduces oxidative stress and inflammation - addressing the three core biological features of bipolar depression. Thus, the Trimetazidine In bipolar DEpression (TIDE) trial repurposes trimetazidine to test its efficacy in treating bipolar depression. The TIDE trial is a randomized, placebo-controlled, double-blinded, with a total recruitment target of 260 participants with bipolar disorder. Eligible participants will complete four visits and receive add-on trimetazidine or placebo across 8 weeks. Allocation to treatment arms will be randomized in a 1:1 ratio using permuted block randomization. An independent statistician will generate and retain the random allocation list. The trial biostatistician and clinicians, participants, their carers and physicians will be blinded to group allocations (i.e., a double-blind design). The effectiveness analysis will assess group differences (i.e., trimetazidine vs. placebo) in the primary outcome measure, the Montgomery Åsberg Depression Rating Scale total score, over the entire study period. The analysis will follow modified intention-to-treat principles and use a Generalized Estimating Equations (GEE) approach. Secondary outcomes include interviews and self-reports measuring global symptomology, anxiety symptoms, quality of life, day-to-day functioning, cognition, overall impairment, fatigue, cost effectiveness, and safety and tolerability data. Bipolar disorder is characterized by dysregulated energy metabolism, and trimetazidine is the first mitochondrial regulator identified as a potential drug to treat bipolar depression. Considering its established safety profile and novel target mechanism, a positive trial outcome may complement or even replace other options and offer an alternative for treating bipolar depression. If successful, its clinical impact could be global, improving health outcomes for hundreds of millions of people living with bipolar disorder. ANZCTR ACTRN12622000474752, registered 25th March 2023.

Background:Depression and anxiety are prevalent in working-aged adults. Although treatment provided by health professionals can improve symptoms and functioning, many people experiencing mental ill-health do not seek help. There have been very few effective interventions to improve help seeking in adults, with none implemented across diverse workplaces through online delivery. Objective:The primary aim of this trial was to test the effectiveness of a co-designed program for increasing professional help seeking intentions in Australian employees, relative to an active control condition. Methods:A triple-blinded, 2-arm cluster randomized controlled trial (N=487; control workplaces: n=26 and intervention workplaces: n=25) was conducted to assess the relative effectiveness of Helipad, a fully automated co-designed single-session interactive program (intervention condition) with a standard psychoeducation program (active control condition). Eligible workplaces (those with ≥50 employees and an employee assistance program; clusters) were recruited via advertising or invited directly by researchers. Eligible participants (employees in a participating Australian workplace, aged ≥18 y, living in Australia, fluent in reading and understanding English, and had access to a device and a reliable internet connection) completed a pretest, immediate posttest, and 6-month follow-up survey sent via email assessing help seeking intentions (primary outcome); mental illness stigma; mental health literacy; help seeking attitudes and behavior; work and activity functioning; quality of life; and symptoms of depression, anxiety, and general psychological distress. Results:A significant difference in change over time in professional help seeking intentions was found between the 2 conditions (F2,185.44=6.89; P=.001), with planned contrasts showing that the Helipad program was effective in increasing professional help seeking intentions compared with the control at the primary end point of immediate posttest (t359.35=-3.72; P<.001). This difference was not maintained at the 6-month follow-up (t119.76=-1.05; P=.30). Retention rates were 71.1% at posttest and 24.9% at follow-up. The Helipad program was also associated with improved mental health literacy and help seeking attitudes at posttest. Helipad was not significantly superior to the control in reducing mental illness stigma or improving professional help seeking behavior; functioning; quality of life; or symptoms of depression, anxiety, or general psychological distress (secondary outcomes) at the 6-month follow-up. A total of 15 people (control: n=9, 4.5%; intervention: n=6, 4.3%) reported adverse events at posttest. Conclusions:This study demonstrated that the co-designed online Helipad program was effective in improving the intentions of employees to seek help from a professional compared to an active control. The program also improved mental health literacy and help seeking attitudes, but these changes were not sustained and did not translate into observable differences in help seeking behaviors or mental health symptoms. This was the first trial of a co-designed intervention to improve mental health help seeking in general workplaces, with previous trials focusing primarily on specific high-risk work environments. Workplace programs that can be delivered at scale may lead to more appropriate engagement with professional mental health care to prevent poor mental health outcomes and increase productivity.

Background There is a lack of research examining whether childhood abuse affects the quality of life (QoL) of individuals living with bipolar disorder and its improvement over the course of treatment.Methods Data from the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder were used to explore the associations between childhood abuse and multiple domains of QoL among 476 outpatients with bipolar disorder. Rates of change in QoL throughout treatment were explored with a series of Generalised Estimation Equations for repeated measures.Results At baseline, childhood abuse was related to poorer QoL in the domains of subjective feelings of wellbeing, social relationships and general activities-but not in physical health or leisure activities. Throughout treatment, participants with a history of childhood abuse reported significantly worse QoL in the same domains, than participants with no history of childhood abuse. Interestingly, exploratory analyses showed that participants with a history of childhood abuse and a current diagnosis of post-traumatic stress disorder (PTSD) had significantly worse QoL in all domains, than participants with no history of childhood abuse or diagnosis of PTSD. There were no significant differences between groups in change in QoL in any of the domains.Conclusion This study comprehensively investigated the relationships between a history of childhood abuse and QoL among people with bipolar disorder who were receiving pharmacotherapy. Although the present findings need to be replicated, they suggest significant impairment in several domains of QoL associated with childhood abuse, which has service and treatment implications for trauma-informed care.Trial Registration ClinicalTrials.gov identifier: NCT01331304

Bipolar disorder is associated with increased mortality from cardiovascular disease, incidence of Metabolic Syndrome (MetS), and obesity. Adverse childhood experiences (ACEs) may contribute to this increased incidence, but findings have been mixed. We aimed to determine associations between ACEs and cardiometabolic risk markers in people with bipolar disorder, and how they change during pharmacological treatment. Data was analysed from 482 participants with bipolar disorder treated for 24 weeks with lithium or quetiapine, comparing those with and without ACEs across cardiometabolic markers. At baseline, those with ACEs had higher body mass indexes but were similar on all other cardiometabolic measures. During the 24-week treatment period, those with ACEs improved slightly more on continuous metabolic syndrome score (cMetS; p = .004), waist circumference, (p = .041) high density lipoproteins (HDL) cholesterol, (p = .028) and diastolic blood pressure (p = .042) than those without ACEs. Sensitivity analysis exploring the role of ACE type revealed that change in HDL was most strongly associated with sexual abuse; higher diastolic blood pressure with emotional abuse; and increased waist circumference with emotional and physical abuse, and higher cMetS with all three ACE types. There were almost no baseline differences in cardiometabolic markers between the ACE and no ACE groups. Those with ACEs seemingly benefitted more from psychiatric treatment regarding their cardiovascular health compared to the no ACE group. Future research should explore links between ACEs and cardiovascular health in those with bipolar disorder, including benefits of psychiatric treatment, the role of specific ACE types, and longer-term outcomes.

Abstract Background The depressive phase of bipolar disorder lasts longer than the manic phase and poses the highest risk due to its negative impact on quality of life and mental health, and peak in suicide attempts. Unfortunately, current therapies for bipolar disorder are far more efficacious in mania than depression, suggesting an urgent need for new and improved therapies for bipolar depression. The literature suggests the chronic presence of low-grade peripheral and central inflammation is a key pathophysiology of depression. In particular, Angiotensin II Type I receptor (AT1R) of the renin-angiotensin system appears to play a critical role in activating the relevant stress, oxidative stress and inflammatory pathways (see Vian et al., 2017, for review). In support of this, cutting-edge genomic studies (e.g. Kidnapillai et al., 2020), findings from animal models of bipolar disorder (e.g. Luo et al., 2020), independent large-scale epidemiological studies (e.g. Johansen et al., 2012) and a meta-analysis (Brownstein et al., 2018) have collectively nominated agents that reduce AT1R activity as a potential novel therapy for depression. Thus, our team designed clinical trials using candesartan, a common anti-hypertensive medication and AT1R blocker, to target this major unmet need in depression. Aims & Objectives The clinical trials aim to investigate the efficacy of adjunctive candesartan versus placebo for the treatment of major depression in unipolar and bipolar disorder. To achieve this aim, two separate trials are run in parallel for participants with either bipolar disorder or major depressive disorder. The two streams are: The Candesartan Adjunctive Bipolar Depression Trial (CADET-BD) and The Candesartan Adjunctive Major Depression Trial (CADET-UD). These trials are the first study of this agent in bipolar and major depressive disorder and will provide important proof-of-principle of the role of the angiotensin system in mood regulation. The primary outcome will measure if candesartan is superior to placebo in reducing depressive symptoms. The secondary outcomes will measure weather candesartan is superior to placebo in reducing anxiety symptoms, inflammatory biomarkers, and improving quality of life, social and work function and cognition. Method Funded by National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF), the CADET trials are both 16-week multi-site double-blind randomized placebo-controlled trials and will aim to recruit 240 participants each (i.e. bipolar depression and unipolar depression). The trials are being conducted at five sites in Australia and each site is equipped with a team of Research Assistants and Principal Investigators to assess participants for inclusion (e.g. moderate to severe depression indexed by a depression rating scale score of 20 or higher), exclusion (e.g. a diagnosis of another psychotic disorder assessed using the SCID-5-RV) and withdrawal criteria, and conduct participant interviews. The participant will first attend the screen visit, followed by six visits within the 16 weeks, either in-person or via telehealth. The participants will complete different sets of tasks at each visit (Figure 1). Results, Discussion & Conclusion The trials are double-blinded and currently recruiting participants. The results, discussion and conclusion will be available once the recruitment is complete. References Brownstein, D.J., Salagre, E., Kö hler, C., Stubbs, B., Vian, J., Pereira, C., Chavarria, V., Karmakar, C., Turner, A., Quevedo, J. and Carvalho, A.F., 2018. Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials. Australian &New Zealand Journal of Psychiatry, 52(1), pp.24-38. Kidnapillai, S., Bortolasci, C.C., Udawela, M., Panizzutti, B., Spolding, B., Connor, T., Sanigorski, A., Dean, O.M., Crowley, T., Jamain, S. and Gray, L., 2020. The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder. The World Journal of Biological Psychiatry, 21(10), pp.775- 783. Luo, H., Wu, P.F., Cao, Y., Jin, M., Shen, T.T., Wang, J., Huang, J.G., Han, Q.Q., He, J.G., Deng, S.L. and Ni, L., 2020. Angiotensin-converting enzyme inhibitor rapidly ameliorates depressive-type behaviors via bradykinin-dependent activation of mammalian target of rapamycin complex 1. Biological Psychiatry, 88 (5), pp.415-425. Johansen, A., Holmen, J., Stewart, R. and Bjerkeset, O., 2012. Anxiety and depression symptoms in arterial hypertension: the influence of antihypertensive treatment. The HUNT study, Norway. European journal of epidemiology, 27, pp.63-72. Vian, J., Pereira, C., Chavarria, V., Kö hler, C., Stubbs, B., Quevedo, J., Kim, S.W., Carvalho, A.F., Berk, M. and Fernandes, B.S., 2017. The renin– angiotensin system: a possible new target for depression. BMC medicine, 15, pp.1-13.

ABSTRACTIntroductionPost‐traumatic stress disorder (PTSD) is more prevalent in those with bipolar disorder (BD) than in the general population, with rates of PTSD as high as 55% in some BD cohorts. Despite this, little research explores the effects of pharmacotherapy treatments in those with comorbid BD and PTSD. This study aims to explore patterns of pharmacotherapy use at baseline and their impact on symptoms in individuals with BD alone and comorbid BD and PTSD.MethodsThe Systematic Treatment Enhancement Program for BD (STEP‐BD) cohort was utilised to examine and compare BD symptoms and pharmacotherapy treatments between those with BD alone (n = 3393) and those with comorbid BD and PTSD (n = 304). We conducted regression models to compare those with and without comorbid PTSD. Models included measures of depression, mania, functioning and quality of life over 24 months of the STEP‐BD study. We included baseline pharmacotherapies (lithium, valproate, antidepressants, antipsychotics and benzodiazepines) as predictor outcome variables in all models.ResultsAt baseline, reported use of lithium was lower in the comorbid BD and PTSD group, while the use of antidepressants, antipsychotics and benzodiazepines was significantly higher in the comorbid BD and PTSD than in the BD alone group. Benzodiazepine use was associated with a small improvement in depression symptom scores and poorer quality of life in those with comorbid BD and PTSD. Lastly, those with comorbid PTSD experienced higher levels of mania and depression symptoms and lower functioning and quality of life compared to BD alone, irrespective of pharmacotherapy treatment.ConclusionClinical trial participants with BD and PTSD reported worse symptoms and outcomes across 24 months of the STEP‐BD study compared to those without comorbid PTSD, regardless of baseline medication use. These results highlight the importance of considering comorbidity in the treatment of mental health conditions, specifically BD, and the need for further exploration of effective treatment options.

Methamphetamine use disorder is a pressing global health issue, often accompanied by significant cognitive deficits that impair daily functioning and quality of life and complicate treatment. Emerging evidence highlights the potential role of genetic factors in methamphetamine use disorder, particularly in association with cognitive function. This review examines the key genetic and cognitive dimensions and their interplay in methamphetamine use disorder. There is converging evidence from several studies that genetic polymorphisms in BDNF, FAAH, SLC18A1, and SLC18A2 are associated with protection against or susceptibility to the disorder. In addition, people with methamphetamine use disorder consistently displayed impairments in cognitive flexibility and inhibitory control compared with people without the disorder. These cognitive domains were associated with reactivity to methamphetamine cues that were positively correlated with total years of methamphetamine use history. Emerging research also suggests that inhibitory control is negatively correlated with lower blood FAAH mRNA levels, while cognitive flexibility positively correlates with higher blood SLC18A2 mRNA levels, highlighting how genetic and cognitive dimensions interact in methamphetamine use disorder. We also include some future directions, emphasizing potential personalized therapeutic strategies that integrate genetic and cognitive insights. By drawing attention to the interplay between genes and cognition, we hope to advance our understanding of methamphetamine use disorder and inform the development of targeted interventions.

This is the first in a series of Position Papers from the Mental Health Australia General Clinical Trials Network (MAGNET) intended to promote the standard of mental health research in Australia. This paper focuses on improving the quality and safety of non-pharmacological trials with a mental health focus, which for the purpose of this paper, are those testing ‘complex’ behavioural interventions (including lifestyle or psychotherapy interventions) with clinical populations. This is timely after last year’s update of the National Statement for Ethical Conduct in Human Research which is intended to provide extended guidance on assessing, mitigating and managing risk and the introduction of the Australian Commission on Safety & Quality in Healthcare’s National Clinical Trials Governance Framework. However, what the implementation of these research policies means for behavioural trials in mental health, given their many nuances, is only being realised. This paper outlines historical issues in the conduct of behavioural trials in mental health (lack of consensus on the concept of harm; lack of governance and inconsistent data collection and/or trial procedures around harms). Next, we detail the methods for developing recommendations to aid triallists’ monitoring and assessing safety during the conduct of behavioural mental health trials that evaluate lifestyle or psychotherapy interventions in clinical populations. Finally, we present a decision-making algorithm to support implementation. Ultimately, we intend to promote quality and safety of behavioural interventions in mental health, to better understand the risk/benefit profile of these treatments and to minimise unnecessary risk to participants and triallists.

AIMS:The study aimed to explore the recent scientific literature regarding the knowledge, attitudes and practices of informal caregivers towards supporting a person with astroke. DESIGN:This study was a scoping review that followed the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Scoping Review extension) guidelines. DATA SOURCES:Searches were conducted across Medline, CINAHL, PsycINFO, EMBASE, Cochrane, SCOPUS and Web of Science from January 2009 to January 2024. REVIEW METHODS:The search results from the various database sources were collated in EndNote 20 and duplicates were removed. Following the removal of duplicates, the studies were imported to Covidence and filtered based on the well-defined eligibility criteria. Three reviewers independently conducted screening and data extraction, and any conflicts were resolved through discussion. RESULTS:The analysis included a total of 37 studies that focused on the knowledge, attitudes and practices related to stroke caregiving. Of these, 15 studies addressed knowledge, 24 studies examined attitudes and 33 studies looked at caregiver practices. CONCLUSION:This scoping review finds that lack of knowledge impacts the attitudes and practices of informal stroke caregivers. With the increasing incidence of stroke and the growing number of caregivers, there is an urgent need for targeted, individualised interventions accompanied by comprehensive evaluation. IMPACT:Caregivers of people with stroke are often unprepared to provide care. Further research is needed to support these individuals, ensuring improved quality of life and better health outcomes for both the caregiver and the person with stroke. PATIENT OR PUBLIC CONTRIBUTION:Not applicable.

The aim of this article is to review the neurobiological changes associated with methamphetamine use disorder (MUD) and consider what implications they have for the development of effective pharmacotherapies. Novel pharmacotherapies are urgently needed to address the complex neurobiological changes that occur both during and after MUD. Current approaches are modelled on maintenance therapies for opioid use, particularly with the use of prescription stimulant medications to substitute for illicit methamphetamine. Existing evidence suggests that these have limited effectiveness, and enthusiasm has been dampened by concerns about the risk of toxicity. We identify an opportunity to look beyond maintenance therapies and to consider alternative models of pharmacotherapy that support the initiation and maintenance of abstinence. In doing this, we highlight the complexity of the neurobiological changes that occur both during and after cessation of methamphetamine use. We identify a need for pharmacotherapies that can address the lasting neurobiological changes from long-term methamphetamine use to improve treatment engagement and retention as well as functional recovery and to reduce relapse risk.

IntroductionData sharing is the practice of making de-identified participant-level data available for use by other researchers. It increases the potential of a dataset to answer new questions, accelerates knowledge creation and increases research integrity by allowing conclusions to be replicated, verified or corrected. Data sharing helps fulfil the ethical obligation to make the most of research participants' contributions to science.Analysis and EvidenceThere is evidence that research participants and the general public are supportive of data sharing. However, those who conducted the original studies may be reluctant to share data, and datasets may be difficult to access, and there may be ethical and governance concerns.DiscussionThis paper describes the Mental Health Node, an Australian Government initiative that aims to increase mental health data sharing. The Mental Health Node works with primary researchers (those who conduct original studies), and secondary researchers (those who reuse data generated by others) to promote ethical data sharing that respects the role of primary researchers and the privacy concerns of research participants.ConclusionPrimary and secondary researchers can collaborate to maximise the value of data collected. This paper includes recommendations for good practice in data sharing and links to resources.

BACKGROUND:Despite higher suicide rates, men are less likely to seek psychological help than women, and even when they do seek help, services are often ill-equipped to meet their needs and maintain their ongoing engagement in care. AIMS:This study aimed to systematically scope the existing literature to summarise research findings and identify gaps related to the association between gender norm conformity (incorporating masculinities and femininities) and psychological help-seeking and treatment engagement. METHODS:A search of MEDLINE, EMBASE, APA PsycINFO and CINAHL databases was conducted. Of 3,652 identified studies, 82 met inclusion criteria. Data from included studies was extracted and synthesised thematically. RESULTS:Findings from the included studies suggested heightened conformity to masculine gender norms was linked with lower help-seeking and treatment engagement, and preliminary evidence was found for positive relationships between feminine gender norm conformity and both help-seeking and treatment engagement. Strength-based approaches to improving men's engagement with psychological services were often recommended, yet the prevailing position on masculinities was deficit-based. CONCLUSIONS:Further research is needed to explore the role of femininities and masculinities in men's help-seeking, and to further examine men's treatment engagement. Researchers are also encouraged to shift toward a strength-based position regarding masculinities in the context of men's mental health.