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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.

Introduction: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million). Methods: This is a longitudinal health record linkage, 2011–2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included. Results: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 61.7% female); unintentional poisoning/animals/plants (median age 43 years, 45% female); and adverse drug reactions (median age 70 years, 54% female). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively. Discussion: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia. Conclusions: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period. [ABSTRACT FROM AUTHOR]

Ketamine is a restricted and regulated medication in Australia and New Zealand, which has implications when considering treatment for patients with treatment-resistant depression and a history of illicit drug use, abuse or dependence. Regulations governing prescription of ketamine for treatment-resistant depression vary between jurisdictions in Australia and New Zealand, though most restrict use in those with drug dependence. There is substantial variation in definitions of drug dependence used in each jurisdiction, and between the legal and clinical definitions, with the latter specified in the current International Classification of Diseases, Eleventh Revision and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This paper reviews the literature assessing the risk of ketamine misuse and dependence in patients with a history of illicit drug use, abuse or dependence and presents recommendations for psychiatrists who prescribe ketamine in such patients with treatment-resistant depression. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

Aims: Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. Methods: Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital‐based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46–82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost‐reduction in patient sub‐populations. Conclusions: Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital‐based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions. [ABSTRACT FROM AUTHOR]

Introduction: The Sydney Medically Supervised Injecting Centre provides a safe, non‐judgemental space where people can inject pre‐obtained substances under the supervision of trained staff. This article describes an unusual incident occurring at the Medically Supervised Injecting Centre in January 2023. Case Presentation: Two regular male clients attending the Medically Supervised Injecting Centre injected a substance they believed to be cocaine. Both clients experienced adverse reactions; one was transported to hospital, while the other became extremely distressed and agitated. Paraphernalia sent for testing returned a result of tiletamine (a dissociative used in veterinary medicine) and no cocaine, 30 h after the incident. Discussion and Conclusions: Where substances are novel or unknown, adverse events are often unexpected and may be more difficult to prepare for. Substance‐induced acute agitation can be alarming and hazardous for people consuming drugs and those around them and may pose challenges for staff. There is a substantial evidence base for the benefits of on‐site drug analysis and drug checking in reducing harms related to drug use, and in enhancing drug market monitoring. This incident was successfully managed by Medically Supervised Injecting Centre and hospital staff, with no major consequence, however clinical management could have been improved using point of care drug testing. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

Background: Sustained‐release (SR) tapentadol was listed on Australia's Pharmaceutical Benefits Scheme (PBS) in 2014 for chronic severe pain requiring long‐term opioid treatment. Dispensings have increased since listing despite declining trends in other PBS‐listed opioids. Preferential prescribing of SR opioids may increase the risk of dependence and accidental overdose, particularly when used to treat acute pain. Aims: To explore the quality use of publicly subsidised tapentadol in Australia. Methods: We examined annual initiation rates and patterns of use of tapentadol (SR) in the dispensing records of a 10% random sample of PBS‐eligible Australians (2014–2021). We used national tapentadol sales data to assess the proportion of sales attributable to the PBS. Results: Tapentadol initiation increased from 2014, peaking at 7.5/1000 adult population in 2019 before declining to 5.3/1000 in 2021. We identified 63 766 new users between 2014 and 2020, of whom 92.8% discontinued in the first year following initiation, 58.0% had only a single dispensing and 34.3% had no other opioids dispensed in the 3 months before or after initiation. 27.8% of new users were dispensed tapentadol on the same day as potentially interacting medicines. There was a sustained drop in the proportion of sales attributable to the PBS from June 2020 onwards, from an average of 69.1%, to 63.9% of pack sales. Conclusions: Patterns of use suggest tapentadol (SR) is generally used for short duration. Although most tapentadol sold in Australia is subsidised, there is evidence of a shift towards private sales. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half‐pack size item codes for IR formulations. Design, setting: Population‐based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS‐eligible residents and IQVIA national opioid medicine sales data (PBS‐subsidised and private prescriptions), 28 May 2018 – 6 June 2021. Main outcome measures: Mean amount of PBS‐subsidised opioid medicines dispensed per day and mean overall amount sold per day — each expressed as oral morphine equivalent milligrams (OME) — overall, by formulation type (IR, CR), and by specific formulation. Results: During the twelve months following the PBS changes, daily PBS‐subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, –106 146 to –56 984 OME) than the mean daily level for 2018–20, a decline of 3.8% after adjusting for the pre‐intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS‐subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half‐pack sizes comprised 8.4% of PBS‐subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. Conclusions: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS‐subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions. [ABSTRACT FROM AUTHOR]

The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful. [ABSTRACT FROM AUTHOR]

Vancomycin's widespread use as the mainstay antibiotic against methicillin‐resistant Staphylococcus aureus infections is complicated by its narrow therapeutic index. Therapeutic drug monitoring using area under the concentration–time curve (AUC)–guided dosing is recommended to optimize therapy and prevent vancomycin‐associated nephrotoxicity (VAN). In 2018, a consultative therapeutic drug monitoring Advisory Service (the Service) was piloted at an Australian hospital to enable AUC‐guided vancomycin dosing. This study sought to compare the incidence of VAN pre‐ and post‐Service implementation. A 4‐year retrospective observational study of intravenous vancomycin therapy (greater than 48 hours) in adults (aged 18 years or older), spanning 3 years before and 1‐year after implementation of the Service was undertaken. Nephrotoxicity was defined as an increase in serum creatinine concentrations of 26.5 μmol/L or greater or 50% or more from baseline, on 2 or more consecutive days. Univariate analysis was performed to compare patients before and after implementation, and with and without VAN. Independent factors associated with VAN were identified using a multivariate model. In total, 971 courses of vancomycin therapy, administered to 781 patients, were included: 764 courses (603 patients) before implementation and 207 courses (163 patients) after implementation. The incidence of VAN decreased by 5% after Service implementation (15% before implementation vs 10% after implementation; P =.075). Independent factors associated with VAN were sepsis, heart failure, solid‐organ transplant, concomitant piperacillin–tazobactam, and average vancomycin AUC during therapy. In conclusion, there was a nonsignificant trend toward a reduced incidence of VAN after the Service. Larger prospective studies are needed to confirm the efficacy of the Service. [ABSTRACT FROM AUTHOR]

This document contains summaries from the Proceedings of the Toxicology and Poisons Network Australasia (TAPNA) 2023 Annual Scientific Meeting. The summaries cover various topics related to toxicology and poisoning, including the neurological effects of nitrous oxide abuse, managing poisoned patients at risk for QT interval prolongation, the misuse of amygdalin/cyanogenic glycoside products for cancer therapy, premature death after self-poisoning, a state-wide poisoning data linkage cohort in New South Wales, methaemoglobinemia caused by ingesting alkyl nitrites, and using screening questions to identify substance use disorder in patients presenting with deliberate self-poisoning. Other summaries discuss cases of aspiration pneumonitis in a clinical toxicology unit, marine animal envenomation and poisoning in Malaysia, the partitioning of methadone in blood and plasma, the management of accidental pediatric liquid paracetamol exposures, a case of non-fatal intoxication from the inhalation of synthetic opioid protonitazene through a vape product, and the use of funnel-web spider antivenom in hospitals in New South Wales and the Australian Capital Territory. The summaries provide valuable information for further research and highlight emerging risks and recommendations in the field of toxicology and poisoning. [Extracted from the article]

Aims: There are increasing concerns about harms related to suboptimal antipsychotic use. Here we describe recent population‐based trends in antipsychotic use and harms in Australia and identify population groups exhibiting patterns of use likely to contribute to these harms. Methods: Using population‐based data from the Australian Pharmaceutical Benefits Scheme (2015‐2020), poisoning calls to the New South Wales (NSW) Poisons Information Centre (2015‐2020) and poisoning deaths in all coronial records (2005‐2018) in Australia, we measured trends in the prevalence of antipsychotic use and related deaths and poisonings. We applied latent class analyses to identify patterns of antipsychotic use that may contribute to harms. Results: Quetiapine and olanzapine had the highest prevalence of use between 2015 and 2020. Noteworthy trends included increases of 9.1% and 30.8% in quetiapine use and poisonings, while olanzapine use decreased by 4.5% but poisonings increased by 32.7%. Quetiapine and olanzapine poisonings and related deaths had the highest rates of co‐ingestion of opioids, benzodiazepines and pregabalin compared to other antipsychotics. We identified six distinct population groups using antipsychotics: (i) ongoing high‐dose use with sedatives (8%), (ii) ongoing use (42%), (iii) ongoing use with analgesics and sedatives (11%), (iv) long‐term low‐dose use (9%), (v) sporadic use (20%) and (vi) sporadic use with analgesics (10%). Conclusion: Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for example through prescription monitoring systems. [ABSTRACT FROM AUTHOR]

Background and aims: New therapeutic options such as lisdexamfetamine and guanfacine have recently become available for the treatment of attention deficit hyperactivity disorder. We described contemporary patterns of attention deficit hyperactivity disorder medicine use among children, adolescents and adults in Australia. Methods: This population-based study used dispensing data for a 10% random sample of Australian residents between July 2012 and December 2020. We estimated the annual prevalence and incidence of attention deficit hyperactivity disorder medicines, second-line guanfacine use and examined concurrent medicine use of both stimulants and non-stimulants. We followed incident users for up to 5 years and analysed treatment persistence using a novel proportion of people covered method. Analyses were stratified by attention deficit hyperactivity disorder medicine, sex and age group; young children (0–5 years), children (6–12 years), adolescents (13–17 years), young adults (18–24 years) and adults (⩾25 years). Results: We observed a twofold increase in the overall prevalence of attention deficit hyperactivity disorder medicine use between 2013 and 2020, from 4.9 to 9.7 per 1000 persons. Incident use also increased across all age groups and both sexes, with the most pronounced increases among adolescent females (from 1.4 to 5.3 per 1000 persons). Stimulant treatment persistence after 5 years was highest among those initiating treatment as young children (64%) and children (69%) and lowest among those initiating treatment in adolescence (19%). Concurrent use of stimulants and non-stimulants was more common among males and younger age groups. Most children (87%) initiating guanfacine had prior dispensings of attention deficit hyperactivity disorder medicines. Conclusion: We observed increasing attention deficit hyperactivity disorder medicine use in Australia, especially among young females. Nevertheless, treatment rates remain lower than the estimated prevalence of attention deficit hyperactivity disorder across all subpopulations. Poor long-term treatment persistence in adolescence may warrant improved clinical monitoring of attention deficit hyperactivity disorder in patients transitioning from paediatric to adult care. Reassuringly, use of newly approved guanfacine appeared to be in accordance with guidelines among children. [ABSTRACT FROM AUTHOR]