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BackgroundThere are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.MethodsThis is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles.DiscussionThis trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Objective: Harmonized tools are essential for reliable data sharing and accurate identification of relevant factors in mental health research. The primary objective of this study was to create a harmonized questionnaire to collect demographic, clinical and behavioral data in diverse clinical trials in adult psychiatry. Methods: We conducted a literature review and examined 24 questionnaires used in previously published randomized controlled trials in psychiatry, identifying a total of 27 domains previously explored. Using a Delphi-method process, a task force team comprising experts in psychiatry, epidemiology and statistics selected 15 essential domains for inclusion in the final questionnaire. Results: The final selection resulted in a concise set of 22 questions. These questions cover factors such as age, sex, gender, ancestry, education, living arrangement, employment status, home location, relationship status, and history of medical and mental illness. Behavioral factors like physical activity, diet, smoking, alcohol and illicit drug use were also included, along with one question addressing family history of mental illness. Income was excluded due to high confounding and redundancy, while language was included as a measure of migration status. Conclusion: The recommendation and adoption of this harmonized tool for the assessment of demographic, clinical and behavioral data in mental health research can enhance data consistency and enable comparability across clinical trials. [ABSTRACT FROM AUTHOR]

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Aims: To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis. Design: Secondary analysis of 13 contiguous 1‐week periods of data (1370 weeks). A risk modification framework was used to test each scenario. Setting: Geelong, Wollongong and Melbourne, Australia. Participants: Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment. Measurements Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self‐reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. Findings The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3–4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9–7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0–7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3–1.8), but there was a small non‐significant excess risk due to the interaction (0.20 95% CI = −1.63 to 2.03). Conclusions: Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population. [ABSTRACT FROM AUTHOR]

Objective: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (＋4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder. [ABSTRACT FROM AUTHOR]

Objective: N-acetylcysteine (NAC) is a novel therapeutic agent with multiple mechanisms of action in the central nervous system and a favourable side effect profile. Clinical evidence indicates that adjunctive NAC may reduce the severity of depressive symptoms in individuals with major depressive disorder (MDD). Methods: A 12-week randomised controlled trial of 2,000 mg/day adjunctive NAC for MDD found no significant improvement at the primary endpoint (week 12) but did see improvements at the post-discontinuation interview (week 16). Within the context of patient-centered treatment, mixed-methods qualitative analysis was also included to explore factors that may determine individual responses to adjunctive NAC treatment. These data were drawn, under blinded conditions, from clinician notes recorded in the case report form. Using the DSM-5 symptom profile for MDD as the initial framework, themes were developed and explored. Frequencies were compared between placebo and NAC groups. Results: Per protocol analysis of individual themes across the six interviews revealed group differences in favour of NAC for overall depressive affect, optimism, relationships and reduced functional impairment. Conclusion: This study provides further evidence for the utility of the mixed methods approach complimenting the primary findings using traditional quantitative analyses, as well as being able to capture additional, often more subtle, evidence of individual symptom-level change that reflects improvement in functional abilities in response to NAC supplementation. The use of mixed methods to explore outcomes from psychiatric studies should be considered in future to work towards improved patient-centred care and both confirm quantitative findings and generate novel hypotheses. [ABSTRACT FROM AUTHOR]

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer's disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma is related to an increased number of depressive episodes and more severe depressive symptoms in bipolar disorder. The evaluation of the networks of depressive symptoms—or the patterns of relationships between individual symptoms—among people with bipolar disorder with and without a history of childhood trauma may assist in further clarifying this complex relationship. Methods: Data from over 500 participants from the Heinz C. Prechter Longitudinal Study of Bipolar Disorder were used to construct a series of regularised Gaussian Graphical Models. The networks of individual depressive symptoms—self‐reported (Patient Health Questionnaire—9; n = 543) and clinician‐rated (Hamilton Depression Rating Scale—17; n = 529)—among participants with bipolar disorder with and without a history of childhood trauma (Childhood Trauma Questionnaire) were characterised and compared. Results: Across the sets of networks, depressed mood consistently emerged as a central symptom (as indicated by strength centrality and expected influence); regardless of participants' history of childhood trauma. Additionally, feelings of worthlessness emerged as a key symptom in the network of self‐reported depressive symptoms among participants with—but not without—a history of childhood trauma. Conclusion: The present analyses—although exploratory—provide nuanced insights into the impact of childhood trauma on the presentation of depressive symptoms in bipolar disorder, which have the potential to aid detection and inform targeted intervention development. [ABSTRACT FROM AUTHOR]

Aims: Treatment of methamphetamine dependence requires monitoring of recent use or abstinence. Self‐report is commonly used for routine monitoring, but the accuracy of self‐report is not established. For the treating clinician, the key accuracy statistic is the negative predictive value (NPV). The study aim was to estimate the NPV of self‐reported non‐use of methamphetamine compared with an oral fluid reference standard. Design, Setting and Participants: This study was a secondary (subgroup) analysis from a randomized controlled pharmacotherapy trial. Three Australian outpatient addiction services took part. Particpants were 139 people dependent on methamphetamine. Measurements: Weekly oral fluid samples over 12 weeks to determine methamphetamine (and amphetamine) concentrations were used as the reference standard. Self‐report of any methamphetamine use in the previous 7 days by the time‐line follow‐back method was the index test. Standard diagnostic accuracy statistics were calculated for all available paired episodes (n = 1134). Three NPV values were calculated: unadjusted NPV and NPV adjusted for clustering of observations through logistic regression and generalized estimating equation (GEE). We also calculated the NPVs for a range of prevalence rates of methamphetamine use, for the calculated levels of sensitivity and specificity. Findings Sensitivity was 96.4% [95% confidence interval (CI) = 95–97.5], specificity was 63.7% (95% CI = 57.3–69.8) and positive predictive value (PPV) was 90.8% (95% CI = 88.8–92.6). The unadjusted NPV was 82.7% (95% CI = 76.5–87.9), adjusted NPV by logistic regression 82.7% (95% CI = 73.9–91.5) and GEE 76.8% (95% CI = 66.8–86.8). At a methamphetamine use prevalence of 5%, the estimated NPV would be 99.7% (95% CI = 99.6–99.9) and at 95% prevalence, 48.2% (95% CI = 39.6–57.0). Conclusions: Self‐report of no recent methamphetamine use appears to be sufficiently accurate to be clinically useful at the expected prevalence rates of methamphetamine use in clinical treatment settings. If generalizable to clinical settings, where these tests are routinely conducted, this may permit a reduction in the frequency and cost of oral fluid assays. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is prevalent and often highly burdensome in people with schizophrenia. The aim of this study was to investigate if mangosteen (Garcinia mangostana Linn.) pericarp extract may be an effective intervention to improve cognitive performance in this population. Methods: This was a secondary analysis of a larger randomized placebo-controlled trial that investigated a 24-weeks intervention of mangosteen pericarp extract supplementation in people diagnosed with schizophrenia. A subset of n = 114 participants with completed cognitive outcomes at follow up were included in this analysis. Using the Cogstate Brief Battery, the following cognitive outcomes were assessed: psychomotor function, attention, visual learning and memory (visual and working). Subgroup analyses investigated whether baseline clinical parameters (baseline cognitive functioning, illness severity and duration, depressive symptoms) moderated the relationship between mangosteen pericarp extract intervention and change in cognitive outcomes. Results: There were no significant between-group changes in any cognitive outcomes assessed. Subgroup analysis based on baseline cognition and clinical characteristics did not reveal any significant between-group difference in change. Conclusions: Mangosteen pericarp extract did not affect cognitive outcomes in people with schizophrenia. Further investigation regarding optimal dosing strategies for mangosteen interventions and the testing of additional cognitive domains may be warranted. Trial Registration: ANZCTR.org.au identifier: ACTRN12616000859482, registered 30 June 3 2016. [ABSTRACT FROM AUTHOR]

Objectives: Garcinia mangostana Linn. ("mangosteen") pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. Methods: People diagnosed with schizophrenia or schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. Results: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. Conclusion: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder. [ABSTRACT FROM AUTHOR]

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that Garcinia mangostana Linn. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders. [ABSTRACT FROM AUTHOR]

It is estimated that up to 50 % of people with bipolar disorder (BD) also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the presentation and treatment of people with this comorbidity. Data from 577 individuals diagnosed with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study of BD were explored at baseline, year two and four. Three trauma groups were created: (i) one trauma (n = 75), (ii) multiple traumas (n = 417), and comorbid PTSD (n = 85). Measures of depression, mania, sleep, number of hospitalisations, suicide attempts, and medication use were analysed using regression modelling to determine differences between the three trauma groups. There was an increase in depression, mania, and sleep scores and a higher number of hospitalisations in participants with comorbid PTSD compared to those experiencing one trauma. Additionally, increased mania and depression scores were reported in participants experiencing multiple traumas compared to those with one trauma. There was no difference in medication use between those who experienced one trauma compared to those with comorbid PTSD. The trauma groups may include confounding with more participants experiencing PTSD than reported in this study due to screening processes. Additionally, the severity of trauma was not recorded, therefore number of traumas was utilised as a proxy. Comorbid BD and PTSD is associated with worse symptom scores compared to participants reporting one trauma. Clinical implications include the addition of trauma-informed care to clinical settings to identify PTSD to provide appropriate treatments. • Comorbid bipolar disorder and PTSD reports worse depression and mania symptoms. • Sleep scores were significantly worse in the comorbid PTSD group. • Increased hospitalisations were reported in the comorbid PTSD group. • Lithium was less likely to be prescribed to the multiple trauma group. • Trends displays sedatives were more likely to be used in the comorbid PTSD group. [ABSTRACT FROM AUTHOR]

Objective: The influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder was systematically reviewed.Methods: Randomised and non-randomised studies of interventions for bipolar disorder that included an assessment of childhood trauma were eligible. MEDLINE Complete, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched. Two independent reviewers completed the screening and extraction process. Two independent reviewers assessed the risk of bias in the included studies using the Cochrane Collaboration's Risk of Bias tool and the Newcastle-Ottawa Scale. Alongside a narrative synthesis, random-effects meta-analyses were performed.Results: Twelve studies (1175 participants) were included. The narrative review highlighted differential treatment outcomes among individuals with a history of childhood trauma. The meta-analyses suggested that childhood trauma was unrelated to treatment response (five studies, 426 participants; odds ratio 0.58, 95% CI 0.27-1.25, p = .164) but may be associated with greater improvement in global functioning (three studies, 210 participants; Hedge's g 0.65, 95% CI 0.04-1.26, p = .037).Limitations: The impact of childhood trauma on the effectiveness of specific pharmacological/psychological interventions could not be explored due to the small body of research identified.Conclusion: The overall quality of the extant evidence is low, which precludes definitive comment on the role of childhood trauma in the treatment of bipolar disorder. Additional research that uses large and representative samples is required to ascertain whether a history of childhood trauma affects the treatment outcomes of interventions for individuals with bipolar disorder. [ABSTRACT FROM AUTHOR]

The aim of this pilot randomised control trial (RCT) was to test, 1) feasibility and acceptability of a surf therapy program to improve symptoms of mental ill-health among children and adolescents, and 2) the design and procedures of an evaluative study. This pilot RCT compared a 6-week mentor-supported surf therapy program with a wait list control group, in Australian children and adolescents aged 8–18yrs (M age = 11.28, SD = 2.34; 15 females), who were help seeking for issues relating to their mental health. Exclusion criteria included if an individual was actively suicidal or experiencing a psychotic episode or being unavailable for program dates. The primary outcome was the feasibility and acceptability of the intervention and study design assessed via 11 pre-defined criteria. A secondary outcome was to investigate the effectiveness signal of the intervention on child indicators of depression and anxiety, assessed via the Revised Children's Anxiety and Depression Scale-Short Form and the Strengths and Difficulties Questionnaire. Random allocation was computer generated and while it was not possible to blind participants, researchers collecting assessments were blinded to group allocation. Thirty-six youth were randomised (intervention = 18; wait list controls = 18), representing an 84% participation rate among eligible youth. Of the 11 a priori feasibility and acceptability criteria, 4 of 5 relating to the intervention, and 4 of 6 addressing the study design were fully met, with the unmet factors guiding program revision. At the completion of the intervention, children and adolescents receiving the intervention reported reductions in symptoms of depression (ES = 0.57), anxiety (ES = 0.43), emotional problems, (ES = 0.79), peer problems (ES = 0.56), hyperactivity/inattention (ES = 0.28), and overall difficulties (ES = 0.64). These reductions were not sustained 6-weeks after completion of the intervention. Surf therapy is an acceptable and feasible intervention for addressing symptoms of mental ill-health among children and adolescents. Preliminary evidence suggests that surf therapy improves symptoms of mental ill-health in the short-term but that these improvements were not sustained after the intervention is ceased. • Children receiving surf therapy had greater reductions in symptoms of mental ill-health than those in the control group. • Mental ill-health symptom reduction was not sustained 6-weeks post program. • Surf therapy is a feasible and acceptable intervention for managing child and adolescent mental ill-health. • A definitive RCT study design is an appropriate next step to assess the mental health effects of surf therapy. [ABSTRACT FROM AUTHOR]