A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial.

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.

The reflections of health service providers on implementing contingency management for methamphetamine use disorder in Australia.

INTRODUCTION: Contingency management (CM) is the most effective treatment for reducing methamphetamine use. We sought to understand why CM has not been taken up to manage methamphetamine use disorder in Australia. METHODS: Six focus groups (4-8 participants per group) were conducted with health workers from agencies in Australia that provided drug-related health care to people who use methamphetamine. These agencies had no previous experience delivering CM for substance use. The potential acceptability and feasibility of implementing CM in their services were discussed. RESULTS: Participants felt that it would be beneficial to have an evidence-based treatment for methamphetamine use disorder. This sentiment was offset by concerns that CM conflicted with a client-centred harm-reduction approach and that it dictated the goal of treatment as abstinence. It was also perceived as potentially coercive and seen to reify the power imbalance in the therapeutic relationship and therefore potentially reinforce stigma. There was also concern about the public's perception and the political acceptability of CM, who would fund CM, and the inequity of providing incentives only to clients with a methamphetamine use disorder. Some concerns could be ameliorated if the goals and structure of CM could be tailored to a client's needs. DISCUSSION AND CONCLUSIONS: Many healthcare workers were keen to offer CM as an effective treatment option for people with methamphetamine use disorder, but CM would need to be sufficiently flexible to allow it to be tailored to client needs and implemented in a way that did not adversely impact the therapeutic relationship.

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention.

INTRODUCTION: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. METHODS: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. RESULTS: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial. DISCUSSION: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

Using the Alcohol, Smoking and Substance Involvement Screening Test to predict substance-related hospitalisation after release from prison: A cohort study.

BACKGROUND AND AIMS: Poor substance use-related health outcomes after release from prison are common. Identifying people at greatest risk of substance use and related harms post-release would help to target support at those most in need. The Alcohol Smoking and Substance Involvement Screening Test (ASSIST) is a validated substance use screener, but its utility in predicting substance-related hospitalisation post-release is unestablished. We measured whether screening for moderate/high-risk substance use on the ASSIST was associated with increased risk of substance-related hospitalisation. DESIGN: A prospective cohort study. SETTING: Prisons in Queensland and Western Australia. PARTICIPANTS: Participants were incarcerated and within 6 weeks of expected release when recruited. A total of 2585 participants were followed up for a median of 873 days. MEASUREMENTS: Baseline survey data were combined with linked unit record administrative hospital data. We used the ASSIST to assess participants for moderate/high-risk cannabis, methamphetamine and heroin use in the 3 months prior to incarceration. We used International Classification of Diseases (ICD) codes to identify substance-related hospitalisations during follow-up. We compared rates of substance-related hospitalisation between those classified as low/no-risk and moderate/high-risk on the ASSIST for each substance. We estimated adjusted hazard ratios (aHR) by ASSIST risk group for each substance using Weibull regression survival analysis allowing for multiple failures. FINDINGS: During follow-up, 158 (6%) participants had cannabis-related, 178 (7%) had opioid-related and 266 (10%) had methamphetamine-related hospitalisation. The hazard rates of substance-related hospitalisation after prison were significantly higher among those who screened moderate/high-risk compared with those screening low risk on the ASSIST for cannabis (aHR 2.38, 95% confidence interval [CI] 1.74, 3.24), methamphetamine (aHR 2.23, 95%CI 1.75, 2.84) and heroin (aHR 5.79, 95%CI 4.41, 7.60). CONCLUSIONS: Incarcerated people with an Alcohol Smoking and Substance Involvement Screening Test (ASSIST) screening of moderate/high-risk substance use appear to have a significantly higher risk of post-release substance-related hospitalisation than those with low risk. Administering the ASSIST during incarceration may inform who has the greatest need for substance use treatment and harm reduction services in prison and after release from prison.

Psychosocial stress and methamphetamine use: A mixed-methods study of intersectional stigma and Aboriginal and Torres Strait Islander methamphetamine use.

BACKGROUND: Regular methamphetamine use can cause a range of physical, psychological and social harms. Stigma is one factor that impacts engagement and successful completion of treatment. In Australia, Aboriginal and Torres Strait Islander people who regularly use methamphetamine experience multiple stigmas, which further compounds access to treatment and quality of life. This paper explores the cumulative and compounding effects of participating in a stigmatised activity such as illicit drug use in relation to the stigma experienced by Aboriginal and Torres Strait Islander people as a population marginalised through colonisation. METHODS: Ten sites nationally participated in a cross-sectional survey measuring a range of factors including psychosocial stress in methamphetamine users. The survey sample size was 734, with 59% identifying as Aboriginal and Torres Strait Islander (n = 433). In addition, a total of 147 mainly Aboriginal and Torres Strait Islander people who use methamphetamine, community and family members, and service providers took part in a total of 19 focus groups and 7 interviews. RESULTS: Aboriginal and Torres Strait Islander participants experienced multiple psychosocial stressors at significantly higher rates than non-Indigenous participants. These stressors include diminished access to health care (33%), experiences of racism (34%), grief and sorrow (39%), worry for family (46%), and child welfare experiences (46%). The qualitative findings highlight the cumulative impact of historical, political and social stressors on an already stigmatised population. CONCLUSIONS: The findings of this unique analysis demonstrate the disruptive impact of methamphetamine use on the lives of those who use methamphetamines and their family members. They also illustrate challenges, such as stigma, that may confront those seeking assistance for drug-related issues. Aboriginal and Torres Strait Islander community involvement is necessary to provide support and education for the individual, the family, and the community as a whole. Stigma reduction is therefore a worthy target for intervention.

Perspectives and sentiments on contingency management from people who use methamphetamine.

INTRODUCTION: Contingency management (CM) is currently the most efficacious treatment for methamphetamine use, yet it is rarely available in routine care. We examined the viewpoints of people who use methamphetamine on CM as a potential treatment for methamphetamine use disorder. METHODS: Semi-structured qualitative interviews with 30 Australians aged 18 years or older who had used methamphetamine at least weekly in the past 6 months. RESULTS: Participants reported overall positive attitudes towards CM as a potential treatment option for methamphetamine use disorder. However, there was need for greater flexibility in meeting participant treatment goals (e.g., reduced use or complete abstinence), with particular concern about the viability of initiating abstinence, both in terms of the sufficiency of the initial financial incentive and managing withdrawal symptoms. There was strong interest in the use of digital technologies to provide remote CM, particularly around the convenience and flexibility this offered. Despite this, participants remained keen to access adjunctive treatment and support services but stressed that engagement with these additional services should not be mandatory. Marketing of CM will need to address preconceptions about drug-testing used in abstinence-based CM being punitive (especially urine testing) and its connotations with criminal justice interventions. DISCUSSION AND CONCLUSION: Positive attitudes towards CM bode well for potential uptake should CM be made available in routine clinical practice. However, there is a need to adapt CM to ensure it is feasible and attractive to people who are seeking treatment for methamphetamine use disorder.

Methamphetamine exposure and depression-A systematic review and meta-analysis.

ISSUES: Methamphetamine use is a public health concern that has been associated with comorbid mental health problems. We aim to better understand the relationship between methamphetamine use and depression by: (i) systematically reviewing and meta-analysing the risks of depression by methamphetamine use; and (ii) investigating the risk of unmeasured confounding. APPROACH: A systematic review and meta-analysis were conducted following PRISMA guidelines. EMBASE, PsycINFO and PubMed were searched to identify human studies reporting on the association between methamphetamine or amphetamine use and depressive outcomes. The data were summarised narratively and meta-analysed, stratified by cross-sectional and longitudinal estimates. Unmeasured confounding was assessed by E-values analyses. KEY FINDINGS: From the 6606 studies that came up from the search, 14 eligible studies were included in the narrative review and had data for meta-analysis. A significant association was found between any use of methamphetamine and any depression outcomes in cross-sectional (odds ratio [OR] = 1.66 [95% confidence interval [CI] 1.34, 2.05]) and longitudinal estimates (OR = 1.18 [95% CI 1.08, 1.28]). People with a methamphetamine use disorder had significantly higher odds of depression than those without (OR = 2.80 [95% CI 1.40, 5.90]). The E-values ranged from 1.28 to 6.30 for cross-sectional studies and from 2.37 to 3.21 for longitudinal studies. CONCLUSION: Based on limited data, people who used methamphetamine have higher odds of depression than people who do not. There were mostly a low to moderate risk of unmeasured confounding in the longitudinal study results. Future longitudinal studies conducted using causal framework methods are warranted.

How does a family history of psychosis influence the risk of methamphetamine-related psychotic symptoms: Evidence from longitudinal panel data.

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.

Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

The health needs of people leaving prison with a history of methamphetamine and/or opioid use.

INTRODUCTION: Methamphetamine use is more common than opioid use among prison entrants in some countries, including Australia, yet most research and policy focuses on opioid use. This suggests that traditional opioid-focused interventions are no longer appropriate for the majority of this group in countries such as Australia. To inform policy and practice, we compared socio-demographic characteristics and health needs of people leaving prison with a history of methamphetamine use and/or opioid use. METHODS: A cross-sectional survey of incarcerated adults administered the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test was used to identify moderate-/high-risk methamphetamine use (n = 909), opioid use (n = 115) or combined methamphetamine/opioid use (n = 356) before incarceration. We compared groups using modified log-linked Poisson regression with robust error variance. RESULTS: Compared to the opioid-only group, the methamphetamine-only group were: significantly more often aged <25 years; significantly more likely to identify as Indigenous; significantly less likely to have a history of prior incarceration, drug injection or overdose. A significantly lower proportion of methamphetamine-only and methamphetamine-and-opioid participants self-reported current hepatitis C infection compared to opioid-only participants. A majority of participants in all groups screened positive for current psychological distress according to the K10. DISCUSSION AND CONCLUSIONS: People leaving prison with a history of methamphetamine use differ from opioid users with respect to demographics, patterns of substance use and related health concerns. Treatment and harm reduction efforts for people who experience incarceration must respond to patterns of drug use in this population, and invest at scale in coordinated, continuous services for co-occurring substance use and mental health problems.

The predictive validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for moderate- to high-risk cannabis, methamphetamine and opioid use after release from prison.

BACKGROUND AND AIMS: Illicit substance use is common among people entering prisons, as is returning to substance use after release from prison. We aimed to assess the predictive validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for returning to substance use after release from prison. DESIGN: A longitudinal design with baseline survey conducted between 2008 and 2010 in the 6 weeks before expected prison release and up to three follow-up surveys in the 6 months after release. SETTING: Prisons in Queensland, Australia. PARTICIPANTS: A total of 1054 adults within 6 weeks of expected release from prison. MEASUREMENTS: The ASSIST was used to assess problematic use of cannabis, methamphetamine, heroin and other non-prescribed opioids in the 3 months before incarceration. Post-incarceration substance use was measured at 1, 3 and 6 months after release. We calculated the area under the receiver operating characteristic curve (AUROC) and the optimal ASSIST cut-off score for each substance, using Youden's index (J). FINDINGS: Forty-one per cent (n = 434) of the cohort reported any substance use during follow-up: 33% (n = 344) used cannabis, 20% (n = 209) methamphetamine, 10% (n = 109) heroin and 9% (n = 97) illicit other opioids. The optimal ASSIST cut-off score was ≥ 4 for heroin, methamphetamine and cannabis and ≥ 1 for other opioids. Using these cut-offs, the AUROC was highest for heroin in predicting both any use (AUROC = 0.82) and weekly use (AUROC = 0.88) in the past 4 weeks. AUROCs for other drugs ranged from 0.73 to 0.79. CONCLUSIONS: The ASSIST shows promise as an accurate and potentially scalable tool that may be useful for predicting a return to substance use after release from prison and could inform service delivery. The substantial rates of returning to substance use after release from prison suggest that prison serves to interrupt rather than cease substance use.

Pharmacological treatment for methamphetamine withdrawal: A systematic review and meta-analysis of randomised controlled trials.

ISSUES: Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008. APPROACH: MEDLINE (1966-2020), CINAHL (1982-2020), PsychINFO (1806-2020) and EMBASE (1947-2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted. KEY FINDINGS: Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established. CONCLUSIONS: There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials.

Methamphetamine use and psychotic symptoms: findings from a New Zealand longitudinal birth cohort.

BACKGROUND: This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort (n = 1265 at birth). METHODS: At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30. RESULTS: After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use. CONCLUSION: Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

Diagnostic accuracy for self-reported methamphetamine use versus oral fluid test as the reference standard in a methamphetamine-dependent intervention trial population.

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.

Lisdexamfetamine for the treatment of acute methamphetamine withdrawal: A pilot feasibility and safety trial.

BACKGROUND: There is no effective treatment for methamphetamine withdrawal. This study aimed to determine the feasibility and safety of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine (MA) withdrawal. METHODS: Open-label, single-arm pilot study, in an inpatient drug and alcohol withdrawal unit assessing a tapering dose of oral lisdexamfetamine dimesylate commencing at 250 mg once daily, reducing by 50 mg per day to 50 mg on Day 5. Measures were assessed daily (days 0-7) with 21-day telephone follow-up. Feasibility was measured by the time taken to enrol the sample. Safety was the number of adverse events (AEs) by system organ class. Retention was the proportion to complete treatment. Other measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), the Amphetamine Withdrawal Questionnaire and craving (Visual Analogue Scale). RESULTS: Ten adults seeking inpatient treatment for MA withdrawal (9 male, median age 37.1 years [IQR 31.7-41.9]), diagnosed with MA use disorder were recruited. The trial was open for 126 days; enroling one participant every 12.6 days. Eight of ten participants completed treatment (Day 5). Two participants left treatment early. There were no treatment-related serious adverse events (SAEs). Forty-seven AEs were recorded, 17 (36%) of which were potentially causally related, all graded as mild severity. Acceptability of the study drug by TSQM was rated at 100% at treatment completion. Withdrawal severity and craving reduced through the admission. CONCLUSION: A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.

Trial protocol of an open label pilot study of lisdexamfetamine for the treatment of acute methamphetamine withdrawal.

INTRODUCTION: 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. METHODS: 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). DISCUSSION: 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.

Trends in methamphetamine use, markets and harms in Australia, 2003-2019.

INTRODUCTION: To describe trends in methamphetamine use, markets and harms in Australia from 2003 to 2019. METHODS: Data comprised patterns of use and price from sentinel samples of people who inject drugs and who use MDMA/other illicit stimulants and population-level amphetamine-related police seizures, arrests, hospitalisations, treatment episodes and deaths from approximately 2003 to 2019. Bayesian autoregressive time-series models were analysed for: no change; constant rate of change; and change over time differing in rate after one to three changepoints. Related indicators were analysed post hoc with identical changepoints. RESULTS: The percentage of people who inject drugs reporting weekly use increased from 2010 to 2013 onwards, while use among samples of people who regularly use ecstasy and other illicit stimulants decreased. Seizures and arrests rose steeply from around 2009/10 to 2014/15 and subsequently plateaued. Price increased ($15.9 [95% credible interval, CrI $9.9, $28.9] per point of crystal per year) from around 2009 to 2011, plateauing and then declining from around 2017. Hospitalisation rates increased steeply from around 2009/10 until 2015/16, with a small subsequent decline. Treatment also increased (19.8 episodes [95% CrI 13.2, 27.6] with amphetamines as the principal drug of concern per 100 000 persons per year) from 2010/11 onwards. Deaths involving amphetamines increased (0.285 per 100 000 persons per year) from 2012 until 2016. DISCUSSION AND CONCLUSIONS: These findings suggest that problematic methamphetamine use and harms escalated from 2010 to 2012 onwards in Australia, with continued demand and a sustained market for methamphetamine. [Correction added on 30 May 2022, after first online publication: In the Abstract under 'Discussion and Conclusions' 'onwards' has been added after … 2010 to 2012].