Explore the vast range of titles available.

IntroductionHarms due to methamphetamine use disorder (MAUD) are rising globally. Untreated withdrawal symptoms perpetuate the cycle of dependence and are a barrier to treatment. There is no pharmacotherapy approved for methamphetamine withdrawal. Lisdexamfetamine (LDX) dimesylate has potential as an agonist therapy to ameliorate symptom severity during acute methamphetamine withdrawal and increase duration of initial abstinence and retention in treatment.Methods and analysisWe will conduct a double-blind, randomised, controlled trial to evaluate the efficacy of LDX in reducing symptom severity during acute methamphetamine (MA) withdrawal. One hundred eighty-four adults with moderate to severe MAUD presenting to a health service requesting MA withdrawal treatment who report use of MA within the last 72 hours will be recruited. Participants will be randomised 1:1 to receive a tapering dose of lisdexamfetamine (250 mg on day 1, reducing by 50 mg per day to 50 mg on day 5, followed by 2 days of placebo washout on days 6 and 7), or placebo for 7 days. The study will be conducted over 7 days in an inpatient unit, and all participants will also receive standard inpatient withdrawal care. Participants will be followed up in the community to day 84. The primary outcome is efficacy, defined as the between-group difference in average withdrawal severity measured over the 7-day admission by the Amphetamine Withdrawal Questionnaire. Secondary outcomes are retention in treatment, treatment satisfaction, sleep and concomitant medication use (symptomatic medications and medications for other indications to day 7); safety, craving for MA, post-treatment withdrawal symptoms, depression, anxiety and stress, insomnia and cost effectiveness (to day 28) and MA use, mental, physical and social health and post-withdrawal treatment utilisation (to day 84). A First Nations qualitative substudy will assess the experiences of Aboriginal and Torres Strait Islander participants, ensuring the treatment meets the needs of First Nations people.Ethics and disseminationThis protocol was first approved by the St Vincent’s Hospital Human Research Ethics Committee on 15/05/2024 (2024/ETH00788). All participants will be provided with a participant information sheet and consent form, be fully informed about the study and given ample time to consider participation. Results will be published in peer-reviewed journals and presented at national and international conferences. Findings will be presented such that individual participants will not be identifiable.Trial registration numberACTRN12624001061527.

Positive psychotic symptoms have consistently been associated with methamphetamine use but the presence of a negative symptom cluster remains unclear. We used exploratory factor analysis to examine whether a discrete negative syndrome could be delineated among methamphetamine users, and to examine the clinical correlates of this syndrome. Participants (N = 154) were people who used methamphetamine at least monthly and did not meet DSM-IV diagnostic criteria for lifetime schizophrenia. Scores on the Brief Psychiatric Rating Scale for the past month were subject to exploratory factor analysis. Latent class analysis was applied to resultant factor scores to determine whether negative and positive factors were experienced by the same participants. Past-month substance use measures were days of use for each drug type and methamphetamine dependence assessed using the Severity of Dependence Scale. We articulated a three-factor model including ‘positive/activation symptoms’ (e.g. suspiciousness, hallucinations, conceptual disorganisation, tension), ‘affective symptoms’ (e.g. depression, anxiety) and ‘negative symptoms’ (e.g. blunted affect, motor retardation). Positive-activation and affective symptoms (but not negative symptoms) were positively correlated with past month days of methamphetamine use (r = 0.16; r = 0.25) and severity of dependence (r = 0.24; r = 0.41). Negative symptoms were correlated with heroin (r = 0.24) and benzodiazepine use (r = 0.21). Latent class analysis revealed a three-class model comprising a positive-symptom class (44%, high positive-activation, low negative symptoms), a negative-symptom class (31%, low positive-activation, high negative symptoms), and a low-symptom class (38%, low on all factors). A negative symptom syndrome exists among people who use methamphetamine, but this appears related to polysubstance use rather than forming a part of the psychotic syndrome associated with methamphetamine use. Overlooking the role of polysubstance use on negative symptoms may conflate the profiles of methamphetamine-associated psychosis and schizophrenia. •A negative syndrome exists in methamphetamine users without schizophrenia (SZ).•This negative syndrome was not correlated with methamphetamine use.•This negative syndrome may be an artefact of depressant use.•Depressant use may obfuscate differences between SZ and methamphetamine psychosis.•Differential diagnosis may be more accurate with complete drug history assessment.

Digital interventions can help to overcome barriers to care, including stigma, geographical distance, and a lack of culturally appropriate treatment options. \"We Can Do This\" is a web-based app that was designed with input from cultural advisors and end users to support Aboriginal and Torres Strait Islander people seeking to stop or reduce their use of methamphetamine and increase psychosocial well-being. This study aimed to evaluate the effectiveness of the \"We Can Do This\" web-based app as a psychosocial treatment for Aboriginal and Torres Strait Islander people who use methamphetamine. The web app was evaluated using a randomized waitlist controlled parallel group trial. Participants were Aboriginal and Torres Strait Islander people aged 16 years or older who self-identified as having used methamphetamine at least weekly for the past 3 months. Participants were randomized on a 1:1 ratio to receive either access to the web-based app for 6 weeks or a waitlist control group. Both groups received access to a website with harm minimization information. The primary outcome was days of methamphetamine use in the past 4 weeks assessed at 1, 2, and 3 months post randomization. Secondary outcomes included severity of methamphetamine dependence (Severity of Dependence Scale [SDS]), psychological distress (Kessler 10 [K10]), help-seeking behavior, and days spent out of role due to methamphetamine use. Participants (N=210) were randomized to receive either access to the web-based app (n=115) or the waitlist control condition (n=95). Follow-up was 63% at 1 month, 57% at 2 months, and 54% at 3 months. There were no significant group differences in days of methamphetamine use in the past 4 weeks at 1 the month (mean difference 0.2 days, 95% CI -1.5 to -2), 2 months (mean difference 0.6 days, 95% CI -1 to 2.4 days) or 3 months (mean difference 1.4 days, 95% CI -0.3 to 3.3 days) follow-up. There were no significant group differences in K10 scores, SDS scores, days out of role, or help-seeking at any of the 3 follow-up timepoints. There was poor adherence to the web-based app, only 20% of participants in the intervention group returned to the web-based app after their initial log-in. Participants cited personal issues and forgetting about the web-based app as the most common reasons for nonadherence. We found poor engagement with this web-based app. The web-based app had no significant effects on methamphetamine use or psychosocial well-being. Poor adherence and low follow-up hindered our ability to accurately evaluate the effectiveness of the web-based app. Future web-based apps for this population need to consider methods to increase participant engagement. Australian New Zealand Clinical Trials Registry ACTRN12619000134123p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376088. RR2-10.2196/14084.

Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients. A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary). This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.

Background Methamphetamine is the second most used illicit drug in Aotearoa New Zealand, after cannabis. Regular and heavy users of methamphetamine are likely to develop methamphetamine use disorder (MUD), and significant health and psychiatric harm. Effective treatments for MUD are limited, and relapses are common. Tū Whakaruruhau is a programme of research that aims to understand what treatment approaches are effective in managing MUD and related physical and psychological harms, in New Zealand. Methods Tū Whakaruruhau comprises two studies. The first study is a 24-month longitudinal cohort study that will follow people receiving treatment and those not in treatment for MUD (outpatient counselling, residential treatment, and detoxification) in the Auckland, Northland, and Waikato regions of New Zealand. Data collection will occur on entry to treatment (baseline), then 3-, 12-, and 24-months later. The primary outcome is self-reported methamphetamine use (days used in the past month) at 12-months. Secondary outcomes include psychiatric comorbidity, polydrug use, change in diagnosis of MUD, criminal involvement, healthcare utilisation, and expectations and experiences of treatment. Three hundred and twenty participants (50% indigenous Māori, 240 in the Treatment Group, 80 in the Non treatment Group) will be sought for 90% power on the primary outcome. The second study is a longitudinal qualitative study involving interviews at baseline, 6-, and 12-months with 30 participants (50% Māori) from the Treatment Group, to explore their expectations of treatment and lived experiences of treatment for MUD over time. Discussion This programme of work will provide the first evidence of treatment outcomes for MUD and the relative effectiveness of the current approaches to treating MUD, in the New Zealand context. It will provide information on what factors predict better and more equitable health outcomes. The incorporation of qualitative interviews will ensure that the participants’ treatment experiences are captured. This will inform perspectives about what treatment approaches work, and do not work, so that the most appropriate interventions are made available to support consumer needs. Findings will be incorporated into relevant reviews, informing practice and policy. Study registration Australian and New Zealand Clinical Trial Registry: ACTRN12623000438651p. Registered 1st May 2023.

IntroductionAmphetamine type stimulant (ATS) use and self-harm are both major public health concerns globally. Use of ATS is associated with a range of health and social problems, and has been increasing internationally in the last decade. Self-harm and ATS use share a number of underlying risk factors and occur at elevated rates in marginalised groups with high rates of exposure to trauma. The relationship between self-harm and ATS use is likely complex, and the causal pathway may run in either direction. A comprehensive review, synthesis and analysis of the evidence are warranted to investigate this relationship and inform policy and practice.Methods and analysisWe will search the Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and Scopus databases for relevant observational studies published in peer-reviewed journals. The initial search was conducted on 5 February 2021, with a final search expected on 1 February 2022. All studies will be independently screened by two reviewers, first on title and abstract, and then on full-text to determine inclusion in the review. We place no restriction on the population that studies investigate, our exposure of interest is both prescription and illicit ATS use, comparators will be those not currently using ATS, and our primary outcome of interest is the prevalence of self-harm. Data will be extracted using a predesigned template, and pooled prevalence and pooled measures of effect for the association between ATS use and self-harm. If sufficient data are available, we will perform multiple meta-analyses to produce pooled measures of effect for each measure of ATS exposure, as well as different population sub-groups. The Methodological Standard for Epidemiological Research scale will be used to assess study quality, and Egger’s test and I2 values will be used to assess publication bias and heterogeneity, respectively.Ethics and disseminationNo ethical approval is required for this review. We will only synthesise information from published studies that were conducted with ethical approval, so no individual participant data will be used. We will disseminate our findings via publication in a peer-reviewed journal, national and international conference presentations, and presentations to stakeholders in the community.Trial registration numberThis study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021226562).

The use of amphetamine-type stimulants (ATS) places a large burden on health services. The aim was to evaluate the effectiveness of a self-guided Web-based intervention (\"breakingtheice\") for ATS users over 6 months via a free-to-access site. We conducted a randomized trial comparing a waitlist control with a fully automated intervention containing 3 modules derived from cognitive behavioral therapy and motivation enhancement. The main outcome was self-reported ATS use in the past 3 months assessed at 3- and 6-month follow-ups using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Secondary outcomes were help-seeking intentions (general help-seeking questionnaire), actual help seeking (actual help-seeking questionnaire), psychological distress (Kessler 10), polydrug use (ASSIST), quality of life (European Health Interview Survey), days out of role, and readiness to change. Follow-up data were evaluated using an intention-to-treat (ITT) analysis with a group by time interaction. We randomized 160 people (intervention: n=81; control: n=79). At 6 months, 38 of 81 (47%) intervention and 41 of 79 (52%) control participants provided data. ATS scores significantly declined for both groups, but the interaction effect was not significant. There were significant ITT time by group interactions for actual help seeking (rate ratio [RR] 2.16; d=0.45) and help-seeking intentions (RR 1.17; d=0.32), with help seeking increasing for the intervention group and declining for the control group. There were also significant interactions for days completely (RR 0.50) and partially (RR 0.74) out of role favoring the intervention group. However, 37% (30/81) of the intervention group did not complete even 1 module. This self-guided Web-based intervention encouraged help seeking associated with ATS use and reduced days out of role, but it did not reduce ATS use. Thus, this program provides a means of engaging with some sections of a difficult-to-reach group to encourage treatment, but a substantial minority remained disengaged. Australian and New Zealand Clinical Trials Registry: ACTRN12611000947909; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343307 (Archived by WebCite at http://www.webcitation.org/6Y0PGGp8q).

Background There 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. Methods This 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. Discussion This 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 registration Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Preventing and treating methamphetamine-related harm in Aboriginal and Torres Strait Islander populations is a significant challenge for health care services. Digital health care may offer opportunities to support individuals and families in ways that complement existing methamphetamine treatment options. This study responds to a community-identified priority as Aboriginal Community Controlled Health Services identified methamphetamine use as a key concern and sought support to respond to the needs of people who use methamphetamine and their families. This paper reports on a process evaluation of the web application's acceptability and feasibility when used by clients and clinicians in residential rehabilitation services and primary care. This study is part of a larger project entitled \"Novel Interventions to address Methamphetamine use in Aboriginal and Torres Strait Islander Communities\" (NIMAC), which seeks to develop culturally appropriate and strengths-based prevention and treatment interventions to reduce methamphetamine related harm. \"We Can Do This\" was a web application developed for Aboriginal and Torres Strait Islander people who are seeking to reduce or stop methamphetamine use. Clinicians and clients who had used the web application were recruited through Aboriginal Community Controlled Health Services and Aboriginal residential rehabilitation services in urban and regional Victoria and South Australia. Unidentified usage data was collected from all participants. After using the web application, those who indicated a willingness to be interviewed were contacted and interviewed by phone or in person and asked about the feasibility and acceptability of the web application. The framework method of analysis was used to structure and summarise the resulting qualitative data. Interviews with 24 clients and 11 clinicians explored the acceptability and feasibility of the web application. Acceptability incorporated the following domains: affective attitude, burden, ethicality, cultural appropriateness, coherence, opportunity cost, perceived effectiveness, and self-efficacy. The evaluation of feasibility assessed barriers and facilitators to the implementation of the program, with a focus on demand, practicality, fidelity, and integration. Results indicated that both clients and clinicians found the web application content coherent, relatable, empowering, and culturally safe. Barriers to using the web application for clients included a lack of internet connectivity and personal issues such as scheduling. Process evaluation is often under-valued. However, as \"We Can Do This\" was new, innovative and targeted a hard-to-reach population, understanding its feasibility and acceptability as a clinical tool was essential to understanding its potential. \"We Can Do This\" is unique as the only evidence-based, culturally appropriate internet-based therapeutic program specifically designed for Aboriginal and Torres Strait Islander people who use methamphetamine. Findings suggest it was both acceptable and feasible as a low-cost adjunct to usual care in residential rehabilitation and primary care settings.