Effect of CYP2D6 genetic variation on patient-reported symptom improvement and side effects among children and adolescents treated with amphetamines.

OBJECTIVES: Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with amphetamines. METHODS: Two hundred fourteen participants aged 6-24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6 . Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects. RESULTS: Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15-11.7, P  = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects. CONCLUSION: Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

In utero exposure to ADHD medication and long-term offspring outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

Cerebral vasculitis associated with drug abuse.

PURPOSE OF REVIEW: To review understand the epidemiology, background, neuropharmacology, and histopathology of literature verified cases, and likely etiopathogenic mechanisms. RECENT FINDINGS: There are only a handful of histologically confirmed patients in the literature with cerebral vasculitis because of drug abuse. SUMMARY: There is little justification for invasive laboratory investigation given the ready availability of highly accurate vascular neuroimaging techniques to dictate management, which usually rests upon avoidance of further exposure and minimizing the secondary neurotoxic effects of the abused substances and polypharmacy use.

How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?: A Pilot Study of 49 Consecutively Referred Medication-Naive Adults With Attention-Deficit/Hyperactivity Disorder.

PURPOSE/BACKGROUND: This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. METHODS/PROCEDURES: Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. FINDINGS/RESULTS: Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. IMPLICATIONS/CONCLUSIONS: Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Clinical Trials for Stimulant Use Disorders: Addressing Heterogeneities That May Undermine Treatment Outcomes.

In recent years, use of cocaine and amphetamines and deaths associated with stimulants have been on the rise, and there are still no FDA-approved medications for stimulant use disorders. One contributing factor may involve heterogeneity. At the neurobiological level, dual dopamine dysfunction may be undermining medication efficacy, suggesting a need for combination pharmacotherapies. At the population level, individual variability is expressed in a number of ways and, if left unaddressed, may interfere with medication efficacy. This chapter reviews studies investigating medications to address dopamine dysfunction, and it also identifies several prominent heterogeneities associated with stimulant (and other substance) use disorders. The chapter has implications for improving interventions to treat stimulant use disorders, and the theme of individual heterogeneity may have broader application across substance use disorders.

Adult attention deficit/hyperactivity disorder in the ambulatory care setting.

Adult attention deficit/hyperactivity disorder (ADHD) is a significant and prevalent disorder. ADHD can impair adults' quality of life, so clinicians in multiple specialties should be able to recognize and treat the disorder. Much of the current literature has focused on childhood ADHD. However, adult ADHD is a common comorbidity in patients with mental illness, and it is essential that patients diagnosed with the disorder are treated appropriately, which can significantly improve outcomes. Adults with untreated ADHD are more likely to have substance dependence, job instability, and an overall poorer quality of life. This article reviews the screening and assessment for adult ADHD along with pharmacologic and nonpharmacologic recommendations for the management of the disorder.

The Supplement Adulterant ß-Methylphenethylamine Increases Blood Pressure by Acting at Peripheral Norepinephrine Transporters.

ß-Methylphenethylamine [(BMPEA), 2-phenylpropan-1-amine] is a structural isomer of amphetamine (1-phenylpropan-2-amine) that has been identified in preworkout and weight loss supplements, yet little information is available about its pharmacology. Here, the neurochemical and cardiovascular effects of BMPEA and its analogs, N-methyl-2-phenylpropan-1-amine (MPPA) and N,N-dimethyl-2-phenylpropan-1-amine (DMPPA), were compared with structurally related amphetamines. As expected, amphetamine and methamphetamine were potent substrate-type releasing agents at dopamine transporters (DATs) and norepinephrine transporters (NETs) in rat brain synaptosomes. BMPEA and MPPA were also substrates at DATs and NETs, but they were at least 10-fold less potent than amphetamine. DMPPA was a weak substrate only at NETs. Importantly, the releasing actions of BMPEA and MPPA were more potent at NETs than DATs. Amphetamine produced significant dose-related increases in blood pressure (BP), heart rate (HR), and locomotor activity in conscious rats fitted with surgically implanted biotelemetry transmitters. BMPEA, MPPA, and DMPPA produced increases in BP that were similar to the effects of amphetamine, but the compounds failed to substantially affect HR or activity. The hypertensive effect of BMPEA was reversed by the α-adrenergic antagonist prazosin but not the ganglionic blocker chlorisondamine. Radioligand binding at various G protein-coupled receptors did not identify nontransporter sites of action that could account for cardiovascular effects of BMPEA or its analogs. Our results show that BMPEA, MPPA, and DMPPA are biologically active. The compounds are unlikely to be abused due to weak effects at DATs, but they could produce adverse cardiovascular effects via substrate activity at peripheral NET sites.

Peripheral vascular manifestation in patients receiving an amphetamine analog: A case series.

Amphetamine and its related derivatives and analogues (ADRA) are highly addictive central nervous system stimulants that are used commonly in the treatment of attention-deficit/hyperactivity disorder and narcolepsy. These medications are associated with many side effects but reports of peripheral arterial manifestations associated with ADRA usage are scarce. We retrospectively reviewed the records of 16 patients (median age 37 years (IQR 31-47), 13 females) referred to a single tertiary referral service while receiving ADRA. Follow-up was available for a median of 3 years (IQR 3-4.5). The most common presentation (62.5%) was mild vasospastic symptoms involving the upper, lower or both extremities. Six patients developed severe manifestations including tissue loss and the need for lower extremity amputation. Most patients (75%) refused to stop the medication during follow-up. Underlying rheumatologic disorders were found in 25% of the patients, and the presence of rheumatologic disease seemed to be associated with more severe vascular manifestations. In conclusion, it is important to search for ADRA usage as part of the differential diagnosis of digital ischemia.

Systematic review and exploratory meta-analysis of the efficacy, safety, and biological effects of psychostimulants and atomoxetine in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Our aim was to summarize the efficacy and safety of atomoxetine, amphetamines, and methylphenidate in schizophrenia. METHODS: We undertook a systematic review, searching PubMed/Scopus/Clinicaltrials.gov for double-blind, randomized, placebo-controlled studies of psychostimulants or atomoxetine in schizophrenia published up to 1 January 2017. A meta-analysis of outcomes reported in two or more studies is presented. RESULTS: We included 22 studies investigating therapeutic effects of stimulants (k=14) or measuring symptomatic worsening/relapse prediction after stimulant challenge (k=6). Six studies of these two groups plus one additional study investigated biological effects of psychostimulants or atomoxetine. No effect resulted from interventional studies on weight loss (k=1), smoking cessation (k=1), and positive symptoms (k=12), and no improvement was reported with atomoxetine (k=3) for negative symptoms, with equivocal findings for negative (k=6) and mood symptoms (k=2) with amphetamines. Attention, processing speed, working memory, problem solving, and executive functions, among others, showed from no to some improvement with atomoxetine (k=3) or amphetamines (k=6). Meta-analysis did not confirm any effect of stimulants in any symptom domain, including negative symptoms, apart from atomoxetine improving problem solving (k=2, standardized mean difference (SMD)=0.73, 95% CI=0.10-1.36, p=0.02, I2=0%), and trending toward significant improvement in executive functions with amphetamines (k=2, SMD=0.80, 95% CI=-1.68 to +0.08, p=0.08, I2=66%). In challenge studies, amphetamines (k=1) did not worsen symptoms, and methylphenidate (k=5) consistently worsened or predicted relapse. Biological effects of atomoxetine (k=1) and amphetamines (k=1) were cortical activation, without change in ß-endorphin (k=1), improved response to antipsychotics after amphetamine challenge (k=2), and an increase of growth hormone-mediated psychosis with methylphenidate (k=2). No major side effects were reported (k=6). CONCLUSIONS: No efficacy for stimulants or atomoxetine on negative symptoms is proven. Atomoxetine or amphetamines may improve cognitive symptoms, while methylphenidate should be avoided in patients with schizophrenia. Insufficient evidence is available to draw firm conclusions.

Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion (CHANTER) Syndrome.

BACKGROUND: Abnormal restricted diffusion on magnetic resonance imaging is often associated with ischemic stroke or anoxic injury, but other conditions can present similarly. We present six cases of an unusual but consistent pattern of restricted diffusion in bilateral hippocampi and cerebellar cortices. This pattern of injury is distinct from typical imaging findings in ischemic, anoxic, or toxic injury, suggesting it may represent an under-recognized clinicoradiographic syndrome. Despite initial presentation with stupor or coma in the context of obstructive hydrocephalus, patients may have acceptable outcomes if offered early intervention. METHODS: We identified an ad hoc series of patients at our two institutions between years 2014 and 2017 who presented to the neurocritical care unit with severe, otherwise unexplained cerebellar edema and retrospectively identified several commonalities in history, presentation, and imaging. RESULTS: Between two institutions, we identified six patients-ages 33-59 years, four male-with similar presentations of decreased level of consciousness in the context of intoxicant exposure, with acute cytotoxic edema of the cerebellar cortex, hippocampi, and aspects of the basal nuclei. All patients presented with severe cerebellar edema which led to obstructive hydrocephalus requiring aggressive medical and/or surgical management. The five patients who survived to discharge demonstrated variable degrees of physical and memory impairment on discharge and at follow-up. CONCLUSIONS: We present findings of a potentially novel syndrome involving a distinct pattern of cerebellar and hippocampal restricted diffusion, with imaging and clinical characteristics distinct from ischemic stroke, hypoxic injury, and known toxidromes and leukoencephalopathies. Given the potential for favorable outcome despite early obstructive hydrocephalus, early identification and treatment of this syndrome are critical.

Association of recreational drug consumption, cardiac toxicity and heart transplantation

Summary: Cardiac toxicity from recreational drug use remains difficult to establish. We report the cases of 3 young patients who were hospitalized for cardiogenic shock. All were bridged to transplantation with implantation of a left ventricular assist device (LVAD). They underwent uneventful heart transplantation. The patients did not have any significant personal or family medical history, but all admitted consuming large quantities of recreational drugs daily. Histological examination of the native heart did not show any inflammation or infiltrative myocardial disease. In this series of young patients presenting in cardiogenic shock with minimal histologic findings on examination of the native hearts, the association between cardiac toxicity and active use of recreational drugs remains a strong possibility. The transplant community should be made aware of this possible association in the current era of legalization and social trivialization of drug consumption.

Intra-Nasally Administered Oligopeptide Lunasin Acts as a Possible Anti-Psychotic Agent in Mice Models.

Background and Objectives: Previously we have shown that synthetic lunasin, a 43 amino acid residue-containing peptide, after its central (intracisternal) administration in mice demonstrated antagonism against dopaminergic drug behavioural effects, indicating a putative antipsychotic/anti-schizophrenic profile of lunasin. The aims of the present studies were: to test whether lunasin would show an influence on the dopaminergic system after intranasal administration, and to examine the effect(s) of lunasin on serotonin and glutamatergic systems, which could play an essential role in antipsychotic action. Materials and Methods: Lunasin was administered intra-nasally at doses 0.1 and 1 nmol/mouse in ICR mice (n = 7-8) and tested in an open field on hyperlocomotion caused by amphetamine; serotonin 5-HT 2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane (DOI); and glutamate NMDA receptor antagonist phencyclidine. Following behavioural testing, the contents of neurotransmitters and their metabolites in brain hemispheres (n = 6-8) were assessed by ultra-high-performance liquid chromatography-time of flight mas-spectrometry (UHPLC-TOF-MS) method. Also, lunasin binding to serotonin receptors was assessed. Results: Lunasin intra-nasally fully normalized hyper-locomotion and brain monoamine levels in amphetamine- and DOI-treated mice brains. Phencyclidine behavioural effects were not influenced. In vitro receptor binding data demonstrated a low affinity of lunasin (at µM concentrations) compared with DOI (nM concentrations) for the 5-HT2A and 5-HT2C receptors. Conclusions: These results demonstrated, for the first time, that the intranasal administration of oligopeptide lunasin normalized mice behaviour and brain monoamine levels in experimental psychosis mice models. Its neuro-regulatory effects indicated a usefulness of this peptide molecule for the design of novel psychotropic agents.

Comprehensive review of cardiovascular toxicity of drugs and related agents.

Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

Maximal strength training improves musculoskeletal health in amphetamine users in clinical treatment.

Amphetamine use leads to impaired skeletal health and elevated risk of osteoporosis. In the current study, we document that maximal strength training (MST), as a part of clinical treatment, works as a countermeasure, improving muscle force generating capacity, body composition, and skeletal health at sites particularly prone to osteoporotic fractures. INTRODUCTION: Amphetamine users have attenuated musculoskeletal health. MST with heavy loads, few repetitions, and emphasis on maximal mobilization in the concentric phase may increase muscle force generating capacity and skeletal health. This study investigated if MST-induced improvements in force generating capacity improved bone mineral density (BMD), trabecular bone score, and body composition in amphetamine users participating in 3-months clinical treatment. METHODS: Of 40 randomized patients, 23 completed the study: 11 in the supervised training group (TG; 8 men, 3 women, 34 ± 10 years) and 12 in the control group (CG; 9 men, 3 women, 32 ± 8 years). The TG performed hack-squat MST three times a week for 12 weeks with an intensity of ~90% of one repetition maximum (1RM). Both groups attended conventional clinical treatment. Pre-training and post-training, we assessed hack-squat 1RM and rate of force development (RFD), BMD, body composition and trabecular bone score by dual X-ray absorptiometry, and serum bone metabolism markers. RESULTS: MST induced increases in 1RM (70%) and RFD (86%), and resulted in BMD improvements at lumbar spine (3.6%) and total hip (2.4%); all improvements were different from CG (p < 0.05). Both the 1RM and RFD increases were associated with BMD improvements (lumbar spine: r = 0.73 (1RM), r = 0.60 (RFD); total hip: r = 0.61 (1RM); all p < 0.05). No differences were observed in trabecular bone score or bone metabolism markers. CONCLUSIONS: MST improved force generating capacity and skeletal health at sites prone to bone loss in amphetamine users, and advocate that MST should be implemented as a clinical strategy to restore the patients' musculoskeletal health.

Fatalities, Cerebral Hemorrhage, and Severe Cardiovascular Toxicity After Exposure to the New Psychoactive Substance 4-Fluoroamphetamine: A Prospective Cohort Study.

STUDY OBJECTIVE: We study adverse health effects after use of the new psychoactive substance 4-fluoroamphetamine. METHODS: All patients who reported 4-fluoroamphetamine exposure and for whom the Dutch Poisons Information Center was consulted by their physician in 2016 were included in a prospective cohort study. The clinical course was investigated through telephone interviews with the physician and/or patient, using standardized questionnaires. 4-Fluoroamphetamine was analyzed in remaining drug material and biological samples with liquid and gas chromatography-mass spectrometry techniques. RESULTS: We included 45 patients, and follow-up with the physician and/or patient was performed in 33 cases. All patients experienced adverse effects after 4-fluoroamphetamine use. Severe toxicity was reported in 8 patients. In 5 of these patients, 4-fluoroamphetamine exposure was confirmed in biological specimens. Severe toxicity that was reported included 2 fatalities, 4 patients with cerebral hemorrhage (1 fatal), 2 patients with inverted Takotsubo's cardiomyopathy, 1 patient with myocardial infarction, 1 patient with acute heart failure, and an overall high prevalence of pronounced hypertension and tachycardia. CONCLUSION: Since the introduction of 4-fluoroamphetamine to the Dutch drug market in 2007, its use continues to increase, possibly because users perceive it as "ecstasy light" and thus relatively safe. However, the proportion of patients with severe toxicity after 4-fluoroamphetamine use is relatively large in our study population. Therefore, users should be warned about the risks of 4-fluoroamphetamine.

Cognitive-behavioural treatment for amphetamine-type stimulants (ATS)-use disorders.

BACKGROUND: Amphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related substances. ATS are highly addictive and prolonged use may result in a series of mental and physical symptoms including anxiety, confusion, insomnia, mood disturbances, cognitive impairments, paranoia, hallucinations and delusion.Currently there is no widely accepted treatment for ATS-use disorder. However, cognitive-behavioural treatment (CBT) is the first-choice treatment. The effectiveness of CBT for other substance-use disorders (e.g. alcohol-, opioid- and cocaine-use disorders) has been well documented and as such this basic treatment approach has been applied to the ATS-use disorder. OBJECTIVES: To investigate the efficacy of cognitive-behavioural treatment for people with ATS-use disorder for reducing ATS use compared to other types of psychotherapy, pharmacotherapy, 12-step facilitation, no intervention or treatment as usual. SEARCH METHODS: We identified randomised controlled trials (RCT) and quasi-RCTs comparing CBT for ATS-use disorders with other types of psychotherapy, pharmacotherapy, 12 step facilitation or no intervention. We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Embase and five other databases up to July 2018. In addition, we examined reference lists of eligible studies and other systematic reviews. We contacted experts in the field. SELECTION CRITERIA: Eligibility criteria consisted of RCTs and quasi-RCTs comparing CBT versus other types of interventions with adult ATS users (aged 18 years or older) diagnosed by any explicit diagnostic system. Primary outcomes included abstinence rate and other indicators of drug-using behaviours. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Only two studies met the eligibility criteria. Both studies were at low risk of selection bias and reporting bias. In one study, almost half of participants in the intervention group dropped out and this study was at high risk of attrition bias. The studies compared a single session of brief CBT or a web-based CBT to a waiting-list control (total sample size across studies of 129). Results were mixed across the studies. For the single-session brief CBT study, two out of five measures of drug use produced significant results, percentage of abstinent days in 90 days (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.11) and dependence symptoms (standardised mean difference (SMD) -0.59, 95% CI -1.16 to -0.02). Little confidence could be placed in the results from this study give the small sample size (25 participants per group) and corresponding large CIs around the observed effects. For the web-based CBT, there was no significant difference across different outcomes. Neither study reported adverse effects. The meta-analytic mean across these two trials for drug use was not significant (SMD -0.28, 95% CI -0.69 to 0.14). In summary, overall quality of evidence was low and there was insufficient evidence to conclude that CBT is effective, or ineffective, at treating ATS use. AUTHORS' CONCLUSIONS: Currently, there is not enough evidence to establish the efficacy of CBT for ATS-use disorders because of a paucity of high-quality research in this area.

Ice in the Outback: the epidemiology of amphetamine-type stimulant-related hospital admissions and presentations to the emergency department in Hedland, Western Australia.

OBJECTIVES: Despite research showing higher use of amphetamine-type stimulants (ATS) in rural areas, limited research has examined the epidemiology of ATS-related presentations and admissions to remote regional centres. To determine the epidemiology of ATS-related (a) Emergency Department (ED) presentations and (b) inpatient admissions over a five-year period at the Hedland Health Campus (HHC) in remote Western Australia. METHODS: A retrospective review of medical records was conducted. Demographic data including gender, age and indigenous status were captured. RESULTS: Four hundred and eighty-two ATS-related hospital presentations were identified during the study period. The most common reason for ED presentation was mental and behavioural problems. Of those presenting, 66% were male and 69% identified as Aboriginal. ATS-related ED presentations increased seven-fold over the study period. Ninety-nine ATS-related inpatient admissions were identified during the study period. Psychotic disorder was the most common reason for admission. Males made up 75% of admissions and 53% identified as Aboriginal. CONCLUSIONS: This study showed a disproportionally high burden of ATS-related harm among Aboriginal people. The number of ATS-related ED presentations and inpatient admissions increased significantly over the study period.