Substance‐related disorders

Objective: To compare computer-delivered and therapist-delivered treatments for people with depression and comorbid addictive disorders.Design: Randomised controlled clinical trial.Setting and participants: Our study was conducted between January 2005 and August 2007 at seven study clinics in rural and urban New South Wales. Participants were 274 people who had a Beck Depression Inventory II (BDI-II) score ≥ 17 and were using alcohol and/or cannabis at harmful levels in the month before baseline. They were self-referred or referred from other sources such as outpatient drug treatment clinics, general practices and non-government support agencies.Interventions: Participants were randomly allocated to receive (1) integrated cognitive behaviour therapy and motivational interviewing (CBT/MI) delivered by a therapist; (2) integrated CBT/MI delivered by computer, with brief therapist assistance at the end of each session (clinician-assisted computerised [CAC] treatment), or (3) person-centred therapy (PCT), consisting of supportive counselling given by a therapist (the control group). All three treatments were delivered according to a manual developed specifically for the study.Main outcome measures: Changes in depression, alcohol use and cannabis use at 3 months after baseline; significant predictors of change in the primary outcome variables.Results: Compared with computer- or therapist-delivered CBT/MI, PCT was associated with significantly less reduction in depression and alcohol consumption at 3 months. CAC therapy was associated with improvement at least equivalent to that achieved by therapist-delivered treatment, with superior results as far as reducing alcohol consumption. Change in depression was significantly predicted by change in alcohol use (in the same direction) and an ability to determine primacy, irrespective of whether this was for drug use or depression. Change in alcohol use was significantly predicted by changes in cannabis use and depression, and change in cannabis use by change in alcohol use. In the regression model, treatment allocation did not independently predict change, but was associated with significant reduction in depression and alcohol use at 3 months.Conclusions: Over a 3-month period, CBT/MI was associated with a better treatment response than supportive counselling. CAC therapy was associated with greater reduction in alcohol use than therapist-delivered treatment.Trial registration number: ACTRN12610000274077.

Frances J Kay-Lambkin BSc(Psych)(Hons), PhD · Amanda L Baker BA(Hons), MPsych, PhD · Brian Kelly BMed, FRANZCP, PhD · Terry J Lewin BComm(Psych)((Hons)

Objective: To determine the prevalence of major depression among people entering treatment for methamphetamine use.Design, setting and participants: The study was a cross-sectional survey involving 41 specialised drug and alcohol treatment agencies in Brisbane and Sydney. Services provided by these agencies included residential rehabilitation, detoxification and counselling. Participants were 400 people entering treatment for methamphetamine use who were recruited from participating treatment agencies between January 2006 and November 2007. Participants underwent a structured, face-to-face, 1.5-hour interview. Assessment instruments included the Composite International Diagnostic Interview and the Short Form 12.Main outcome measure: Diagnosis of a major depressive episode in the year prior to the study.Results: The prevalence of major depression in the year prior to the study was 40% (95% CI, 35%–44%). A noteworthy post-hoc observation was that a further 44% of participants met the symptom criteria for major depression but were excluded from a diagnosis because their symptoms were better accounted for by psychoactive substance use. Both major depression and these latter cases of “substance-induced depression” were associated with severe symptoms of depression, high levels of disability and suicidal ideation.Conclusion: Most people entering treatment programs for methamphetamine use have levels of depression that require clinical management. Making a diagnosis of major depression in the context of heavy methamphetamine use is problematic because of substance-induced symptoms of depression.

Rebecca McKetin BSc(Psych)(Hons), PhD · Daniel I Lubman FRANZCP, FAChAM, PhD · Nicole M Lee BSc(Hons), MAPS, PhD · Joanne E Ross BSc(Hons), PhD · Tim N Slade BSc(Psych), PhD

Objective: To identify the type and proportion of depressive and related mental health disorders in a group of individuals seeking outpatient treatment at an alcohol and other drug (AOD) service.Design, setting and participants: A cross-sectional study using diagnostic interviews with 95 participants (56 men, 39 women) seeking treatment from an AOD service.Main outcome measures: Mental health and substance disorders were measured using the Composite International Diagnostic Interview, Posttraumatic Stress Disorder Checklist, Beck Depression Inventory, and State–Trait Anxiety Inventory (Trait Version).Results: This was a complex group with addiction, mental health and physical health conditions; 76% had a depressive disorder and 71% had an anxiety disorder. Most were diagnosed with at least two mental health disorders and 25% were diagnosed with four or more different disorders. Alcohol and cannabis use were the most commonly diagnosed AOD disorders. Further, those diagnosed with a drug use disorder reported significantly higher levels of depression compared with those with an alcohol-only disorder. Finally, 60% of the sample reported chronic health conditions, with over one-third taking medication for a physical condition on a regular basis.Conclusions: Primary care providers such as general practitioners are likely to be increasingly called on to assess, treat and/or coordinate care of patients with AOD disorders. We show that this group will likely present to their GP with more than one mental health disorder in addition to acute and chronic physical health conditions.

Petra K Staiger PhD · Anna C Thomas PhD · Lina A Ricciardelli PhD · Marita P McCabe PhD

Objective: To estimate the number of deaths among people released from prison in Australia in the 2007–08 financial year, within 4 weeks and 1 year of release.Design, participants and setting: Application of crude mortality rates for ex-prisoners (obtained from two independent, state-based record-linkage studies [New South Wales and Western Australia]) to a national estimate of the number and characteristics of people released from prison in 2007–08.Main outcome measures: Estimated number of deaths among adults released from Australian prisons in 2007–08, within 4 weeks and 1 year of release, classified by age, sex, Indigenous status and cause of death.Results: It was estimated that among people released from prison in 2007–08, between 449 (95% CI, 380–527) and 472 (95% CI, 438–507) died within 1 year of release. Of these, between 68 (95% CI, 56–82) and 138 (95% CI, 101–183) died within 4 weeks of release. Most of these deaths were not drug-related.Conclusion: The estimated annual number of deaths among recently released prisoners in Australia is considerably greater than the annual number of deaths in custody, highlighting the extreme vulnerability of this population on return to the community. There is an urgent need to establish a national system for routine monitoring of ex-prisoner mortality and to continue the duty of care beyond the prison walls.

Stuart A Kinner PhD · David B Preen BSc(Hons), PhD · Azar Kariminia BSc, MSc, PhD · Tony Butler PhD, MSc · Jessica Y Andrews BHSci/Comm(Hons) · Mark Stoové PhD · Matthew Law MA, MSc, PhD

The Australian Government’s decision to raise taxes on ready-to-drink spirit-based beverages (RTDs; “alcopops”) in 2008 caused great controversy. Interest groups have selectively cited evidence to support their points of view. The alcohol industry cited Victorian data from the Australian Secondary Students’ Alcohol and Drug Survey (ASSADS) as evidence that the tax had failed, but closer examination of the data suggests that fewer students are drinking, and fewer are drinking at risky or high-risk levels. Excise data from the first full year after the tax came into effect showed a more than 30% reduction in RTD sales and a 1.5% reduction in total pure alcohol sold in Australia. Although understanding the impact of the alcopops tax will require critical analysis of a range of evidence, sales and ASSADS data suggest that the tax has resulted in reduced consumption of RTDs and total alcohol. The most effective and cost-effective measures for reducing consumption and harm are a comprehensive graduated volumetric alcohol taxation system, a minimum price per standard drink, and special measures for particular products that may cause disproportionate harm. While welcoming the alcopops tax, public health advocates have consistently argued for a comprehensive package of reform that covers pricing, availability and promotion of alcohol, as well as education and treatment services.

Steven J Skov MB BS, MPH, FAFPHM · Tanya N Chikritzhs BA(Hons), GradDipEpidBioStats, PhD · Kypros Kypri BA(Hons), PhD · Peter G Miller PhD · Wayne D Hall BSc, PhD · Michael M Daube BA(Hons), HonDSci · A Rob Moodie MB BS, MPH, FAFPHM

To the Editor: The association between poor hand hygiene of health care workers and nosocomial infection is well established.1 The National Hand Hygiene Initiative2 has been established to improve hand hygiene among health care workers, and the use of ethanol- or isopropanol-based hand sanitisers has been widely adopted in the hospital setting. To encourage their use by health care workers, many hospitals have undertaken extensive education programs and made hand sanitisers with high alcohol content readily available at all points of patient care. An unanticipated but potentially adverse outcome of this campaign is the intentional consumption of hand sanitisers by patients. We report the case of a 45-year-old man, with a history of polysubstance misuse, who was admitted to our institution with epigastric pain in the setting of acute-on-chronic alcohol intake. No evidence of pancreatic or biliary disease was found and the diagnosis of probable alcohol-related gastritis was made. On Day 3 of admission, the patient became increasingly drowsy. Clinical examination showed that he was rousable, and had a Glasgow Coma Scale score of 13. There were no other significant findings. Some hours later, six near-empty 375 mL bottles of Aqium Gel (Ego Pharmaceuticals, Melbourne, Vic), an antibacterial hand sanitiser that has an ethanol content of 66%, were found by the patient’s bedside. Excipients in this gel include thickener, dexpanthenol, dl-alpha-tocopheryl acetate, fragrance, pH neutraliser and water.3 On direct questioning, the patient admitted to intentionally consuming the contents of the hand sanitiser bottles. This was supported by a breath test performed about 40 minutes after the bottles were found, which showed a blood alcohol concentration of 0.271%. Following advice from the Poisons Information Line, supportive therapy was instigated and the patient made an uneventful recovery. Intentional consumption of ethanol- and isopropanol-based hand sanitisers by hospitalised patients has been described in overseas settings and serious adverse outcomes (including the need for intubation) have occurred.4-6 In one emergency department, all removable bottles of alcohol-based hand sanitiser in patient care areas were replaced with non-removable, self-contained dispensers.6 Experience at our institution over the past 6 months suggests that consumption of alcohol-based hand sanitisers by inpatients may be an increasing problem in Australian settings — we are aware of a further three patients who have consumed these products while at our institution. An increased awareness of this practice is required among health care workers in Australia, as it has the potential to create diagnostic dilemmas and lead to serious outcomes, and preventive measures need to be identified and implemented.

Lachlan M Batty · Anna J Brischetto · Ajay C Kevat · Michael J Oldmeadow

To the Editor: We read with interest the article by Ng and colleagues on life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis,1 and wish to present our own experience of four patients presenting to our hospital over a year (Box). The patients all presented with biochemical signs of renal tubular acidosis with severe hypokalaemia and a normal anion gap metabolic acidosis from long-standing misuse of ibuprofen taken in combination with codeine from over-the-counter (OTC) medications. Patients 1 and 2 presented acutely with deliberate misuse that included an ibuprofen–codeine combination product. Both patients subsequently admitted to long-standing misuse of ibuprofen and codeine taken in combination. Patients 3 and 4 presented with constitutional symptoms and generalised weakness with a history of taking large amounts of an ibuprofen–codeine combination product. Both these patients required intensive care unit admission for central venous access and potassium replacement. As in the case series by Ng and colleagues, there was no history to suggest gastrointestinal loss of potassium, and medication histories were negative for drugs known to cause intracellular potassium movement or potassium wasting (eg, diuretics). Ibuprofen cessation, potassium replacement and supportive care resulted in biochemical recovery in all four patients. Opioid addiction appears to be the common thread reported by Ng et al and in our case series. Other case reports support this.2,3 Paracetamol taken in supratherapeutic doses is known to cause hepatotoxicity, and it appears that patients with opioid addiction may now be turning to ibuprofen–codeine combination products. More evidence of the danger of these products comes from a case series reporting 27 patients with ibuprofen–codeine misuse that resulted in significant morbidity, including presentations for opioid dependence, gastrointestinal haemorrhage, hypokalaemia, anaemia and/or renal failure.4 In Australia, ibuprofen–codeine combination products are available OTC, albeit in restricted amounts due to problems related to codeine misuse.1 Further restrictions may need to be considered in light of the significant morbidity related to the ibuprofen component. Baseline laboratory investigations and other characteristics of four patients with ibuprofen-induced renal tubular acidosis* RR Patient 1 Patient 2 Patient 3 Patient 4 Sex, age in years Female, 35 Male, 55 Male, 41 Female, 39 Ibuprofen dose† Unclear, years’ duration 9.0–18.0 g/day 5.0 g/day 8.0 g/day Other medications Amitriptyline 50 mg at night Esomeprazole 40 mg daily Multiple medications Nil Serum pH 7.35–7.45 7.29 7.13 7.26 7.32 Pco2, mmHg 35–45 45 42 30 28 HCO3-, mmol/L 22–32 21 13 13 14 Anion gap, mmol/L 7–17 3 9 12 11 Na+, mmol/L 136–146 137 139 142 135 Cl-, mmol/L 98–106 116 120 120 111 Urea, mmol/L 3.0–8.0 4.7 4.4 3.0 6.9 Creatinine, μmol/L 60–120 70 123 125 99 K+ on presentation, mmol/L 3.5–5.0 2.8 2.9 2.5 1.4 K+ on discharge, mmol/L 3.5–5.0 3.5 3.8 3.7 4.5 RR = reference range. Pco2 = partial pressure of carbon dioxide. HCO3- = bicarbonate ion. Na+ = sodium ion. Cl- = chloride ion. K+ = potassium ion. * Same format as used in Ng et al case series1 to allow direct comparison. † Maximum recommended: 3.2 g/day.

Colin B Page · Paul A Wilson · Aidan Foy · Michael A Downes · Ian M Whyte · Geoffrey K Isbister

To the Editor: We have previously argued that the recent rapid increase in the popularity of low-carbohydrate (“low-carb”) beers, in Australia and other countries, is more a community health risk than a healthy alternative to traditional beers.1 This contention has since been supported by a survey conducted by the Victorian Health Promotion Foundation (VicHealth), which found that “low carbohydrate beer drinkers mistakenly believe these beverages are a healthier choice than other varieties”.2 Seventy-one per cent of respondents believed that low-carbohydrate beer is healthier than full-carbohydrate beer, despite having the same alcohol content. Alarmingly, 15% of respondents indicated that they consume more beer when drinking low-carbohydrate beer because they believe it is healthier than full-carbohydrate beer. The potentially insidious marketing of health benefits for alcohol products has recently been followed by the release of lower-alcohol, lower-calorie wines such as the McWilliam’s Balance range, Cockatoo Ridge’s Low Calorie Brut Cuvée, Beringer Blass’s White Lie, and the JMB Beverages Brightlite range. These are represented as containing a “lower” rather than “low” alcohol content because, at between 6.5% and 9.5% alcohol by volume, these wines clearly contain a far higher alcohol content than the ≤ 1.15% alcohol by volume that is required by Australian food standards to be represented as a low-alcohol product.4 The health-based marketing of these wines is similar to that of low-carb beer — it implies that consuming these products is healthier than consuming traditional versions. This implied health benefit message is reinforced by endorsement of McWilliam’s Balance wines by Weight Watchers and inclusion of these wines in the Weight Watchers diet program, which is followed by over 1.8 million Australians annually.4 According to its manufacturers, “McWilliam’s Balance is destined for incredible consumer demand”.4 McWilliam’s Balance wines contain about one-third less alcohol and one-third fewer kilojoules than regular wines.4 If these wines are being consumed to replace regular wine consumption in the same quantity, they could offer a community health benefit. If they are consumed instead of soft drinks or water in the belief that they are healthier than regular wines, or consumed in larger quantities than regular wine in the belief that they are healthier, they could represent a community health threat. Presently, the Australian Government is considering making alcohol companies display nutritional information and ingredients on all beer, wine and spirits labels as a result of a submission by the Alcohol and other Drugs Council of Australia.5 Governments need to modify food regulations to help make the message more explicit: lower-alcohol, lower-calorie wines are not a licence to drink to your own health.

Stephen P McKenzie · Evie R Leslie · Peter G Miller

The Cancer Council Australia (CCA) Alcohol Working Group has prepared a position statement on alcohol use and cancer. The statement has been reviewed by external experts and endorsed by the CCA Board. Alcohol use is a cause of cancer. Any level of alcohol consumption increases the risk of developing an alcohol-related cancer; the level of risk increases in line with the level of consumption. It is estimated that 5070 cases of cancer (or 5% of all cancers) are attributable to long-term chronic use of alcohol each year in Australia. Together, smoking and alcohol have a synergistic effect on cancer risk, meaning the combined effects of use are significantly greater than the sum of individual risks. Alcohol use may contribute to weight (fat) gain, and greater body fatness is a convincing cause of cancers of the oesophagus, pancreas, bowel, endometrium, kidney and breast (in postmenopausal women). The existing evidence does not justify the promotion of alcohol use to prevent coronary heart disease, as the previously reported role of alcohol in reducing heart disease risk in light-to-moderate drinkers appears to have been overestimated. CCA recommends that to reduce their risk of cancer, people limit their consumption of alcohol, or better still avoid alcohol altogether. For individuals who choose to drink alcohol, CCA recommends that they drink only within the National Health and Medical Research Council guidelines for alcohol consumption.

Margaret H Winstanley BA · Iain S Pratt GradDip(Diet), APD, AEP · Kathryn Chapman BSc, MNutrDiet · Hayley J Griffin BMedSc, MNutrDiet, PhD · Emma J Croager PhD, MBA · Ian N Olver MD, PhD, FRACP · Craig Sinclair MPubPolMgt, GradDipOrgBehav, BEd(Sec) · Terry J Slevin MPH, FPHAA

To the Editor: Frei and colleagues recently drew our attention to combination analgesic misuse-related morbidity.1 The same phenomenon has also been reported in New Zealand.2 About 50 years ago, analgesic misuse was widespread in Australia and commonly involved chronic, excessive use of combination analgesics (including the aspirin–phenacetin–caffeine [APC] products, Bex and Vincent’s Powders). After many years, some people who used APC developed “analgesic nephropathy”, which made up 12%–15% of dialysis cases.3 I recently performed a retrospective chart review of patients who were referred to the Drug and Alcohol Services at the Western Hospital (Melbourne) for excessive compound analgesic use between September 2005 and September 2010. There were 32 patients (18% of all referrals; median age, 38 years; 23 were women). All had some form of chronic pain, had initiated compound analgesic use for acute pain (eg, headache) and all described progressive use of analgesics because of psychogenic effects (eg, “gave me energy”, “helped me forget”). All 32 patients were diagnosed with opioid dependence and had medical and psychiatric problems correlating with their compound analgesic misuse. One patient, a 34-year-old man, reported taking more than 70 codeine–ibuprofen tablets daily and sustained recurrent gastric ulceration, which eventually required surgery. Despite this, he continued to misuse the analgesics until he undertook opioid replacement pharmacotherapy. A 24-year-old man misusing the same analgesic, despite completing a detoxification program, also relapsed and died after bleeding from gastric ulceration.4 Overall, the patient profiles were remarkably similar to those described by Frei and colleagues.1 Combination analgesic misuse appears largely correlated with products containing drugs of dependence (eg, codeine) and the phenomenon of “rebound pain” (ie, pain that recurs after a short-acting analgesic effect wanes, or “medication overuse headache”). Most morbidity and mortality risks associated with combination analgesic misuse are a consequence of chronic overdose of the non-steroidal anti-inflammatory drug and/or paracetamol components. Paracetamol (mostly when in combination with an opioid analgesic) is reported as the commonest cause of acute liver failure in the United States and United Kingdom.5 Another long-term complication can be hearing loss.6 Two patients in my clinic group had hearing loss, and the ear, nose and throat specialist’s opinion was that it was related to analgesic misuse. Dextropropoxyphene–paracetamol combination products are still available in Australia but are no longer available in the UK. I question the need for opioids in combination analgesic products and, if used, they should be restricted to prescription.

Michael A McDonough

To the Editor: A 61-year-old man presented to the emergency department (ED) of a tertiary hospital seeking treatment for alcohol withdrawal after 36 hours of abstinence. He reported central chest pain radiating to the jaw and left arm that had been present for 2 hours before his arrival at the hospital. He had no history of cardiac disease and no known risk factors for coronary artery disease. An electrocardiogram (ECG) showed sinus tachycardia with T-wave inversion in leads V1, V2 and V3. Two hours after the patient’s arrival at the ED, he tested positive for troponin-T. Over the next hour, his ECG showed development of ST elevation of 1–2 mm in leads V3, V4 and V5. Because of severe alcohol withdrawal, his clinical status precluded urgent coronary angiography; and after treatment with diazepam was commenced, the ST elevation that was evident no longer met criteria for urgent angiography. The patient was given standard medical therapy for acute coronary syndrome, including aspirin, clopidogrel and intravenous heparin, while in the ED, along with ongoing diazepam for alcohol withdrawal. He was later admitted to the coronary care unit with a diagnosis of acute coronary syndrome. The next day, an ECG showed development of widespread T-wave inversion in leads V1 to V5. The dynamic ECG changes were not associated with ongoing chest pain. On Day 3 of the patient’s admission, coronary angiography showed normal coronary arteries, and ventriculography showed apical ballooning of the left ventricle, consistent with a diagnosis of takotsubo cardiomyopathy (Box). Treatment with an angiotensin-converting enzyme inhibitor and a β-blocker was commenced. Three months later, follow-up echocardiography showed a return to normal regional and global left ventricular function. Takotsubo cardiomyopathy takes its name from a traditional Japanese octopus trap that has a similar shape to the abnormally contracting left ventricle seen with this condition.1 Typical findings in a patient with takotsubo cardiomyopathy are chest pain associated with emotional or physical stress, with ST segment changes on electrocardiography and apical ballooning on ventriculography, which is generally expected to resolve within weeks to months; troponin level may or may not be positive. The mechanism of this condition has not yet been determined, but it appears likely that it is due to hyperadrenergic-hypercatecholaminergic states (such as alcohol withdrawal) resulting in localised or diffuse coronary vasospasm.2 Takotsubo cardiomyopathy has only rarely been associated with alcohol withdrawal, and has once been reported in a patient with alcohol withdrawal associated with seizures.3,4 Coronary ventriculography image showing apical ballooning of the left ventricle

Angus G Thompson · Joseph Hung

To the Editor: In Australia, addition of thiamine to bread flour (at 6.4 mg/kg) was made mandatory on 1 January 1991 in an effort to reduce the incidence of Wernicke’s encephalopathy and Korsakoff psychosis.1 Recently, an isocratic high-performance liquid chromatography (HPLC) method for the assessment of thiamine, thiamine monophosphate and thiamine diphosphate (TDP) in human erythrocytes has been described.2 This direct method of measuring thiamine in blood is superior to measuring red blood cell transketolase. We used an HPLC reagent kit (Chromsystems Instruments and Chemicals GmbH, Munich, Germany) to measure whole blood TDP concentrations in a population of 156 people who had alcohol use disorders. They were consecutive cases presenting between June and September 2010 at a driver assessment clinic in South Australia after they were convicted of two or more drink-driving offences. Thirty-two people taking a thiamine-containing medication or vitamin supplement were excluded. Based on the Diagnostic and statistical manual of mental disorders, fourth edition, text revision, of the remaining 124 people, 42 fulfilled criteria for “alcohol dependence” and 82 fulfilled criteria for “alcohol abuse” in the preceding 12 months.3 Of those tested, none had biochemical thiamine deficiency (defined as 2 standard deviations below the reference mean TDP concentration [< 66.5 nmol/L]). The lowest whole blood TDP concentration was 106 nmol/L. The highest concentration found was 362 nmol/L. The mean concentration was 217 nmol/L. This value is 2.5 standard deviations above the mean for the reference population (mean, 133 nmol/L; SD, 33 nmol/L).4,5 The reference range (66.5–200 nmol/L) was derived from a population that did not receive thiamine supplementation in foods. The characteristics of the distributions of thiamine concentrations in the Australian and reference populations are shown in the Box. The mean age of our population was 36 years, the youngest person was aged 19 years and the oldest, 73 years. The mean body mass index was 26.6 kg/m2 and the lowest was 18 kg/m2, so this group was not malnourished. The mean daily alcohol intake reported was 22 g/day but there was wide variation (range, 0–272 g/day; SD, 35 g/day). The results from the population with alcohol use disorders show remarkably elevated thiamine concentrations and no evidence of thiamine deficiency. The very high mean concentration of thiamine shows that this population is not at immediate risk of thiamine deficiency. It also suggests that mandatory supplementation of flour with thiamine has raised the baseline concentration of thiamine in Australians. Distribution of thiamine diphosphate (TDP) concentration in an Australian population with alcohol use disorders compared with a reference population4,5

Philip M Crowley · Matt D Gaughwin

To the Editor: I describe two episodes of transient recurrence of psychosis temporally related to ingestion of an “energy drink” in an obese (125 kg) 27-year-old New Zealand Maori man who had been diagnosed with schizophrenia 8 years earlier. The patient had found that risperidone 6 mg/day effectively relieved persecutory ideas and auditory hallucinations. He had stopped using cannabis and alcohol to excess, but continued to drink up to 10 cups of instant coffee throughout the day for a “lift”, apparently without insomnia or other complications. In July 2009, he consumed a 60 mL Demon Shot energy drink and enjoyed an hour-long “buzz”. Repeating the dose did not re-create the desired effect, and instead made him uneasy, irritable and paranoid; for the first time in many months, he had recurrent thoughts, lasting several hours, of people wanting to harm him. One week later, he drank three shots over 15 minutes. He again experienced a buzz and was observed to be emotionally labile — initially laughing and talkative, and later, restless, withdrawn and argumentative. He had a rapid pulse and insomnia. These symptoms subsided over the next day, and when he was back to his usual self after a further 2 days, he described having had paranoid ideas (“gangsters after me ... scared to leave the house”) over several hours after consuming the drinks. His family also associated these symptoms with the drinks, noting a striking similarity to his illness before commencing antipsychotic treatment. He has since avoided energy drinks and continued risperidone monotherapy, remaining stable for 15 months. Demon Shot is a concentrated energy drink, widely available in Australia and New Zealand. The product’s web page describes each “insanely intense” shot as containing 200 mg caffeine, plus taurine, guarana, and B vitamins (http://www.demonenergy.com.au/products/demon-shots). As a regular smoker, the patient does have increased caffeine metabolism, and his response to consuming large amounts of coffee suggests he is not particularly sensitive to caffeine. Nevertheless, he did exceed the maximum recommended dose (two shots per day) on the second occasion, consuming at least 600 mg of caffeine (4.8 mg/kg) virtually as a single dose. The additional presence of guarana extract (48 mg per shot in Australia; unspecified in New Zealand) is probably relevant, as guarana is a further source of caffeine and may have other stimulant properties. Caffeinated drinks are popular among patients being treated for schizophrenia,1 possibly due to partial reversal of the unpleasant effects of dopamine blockade.2 Although case reports3 and a later controlled study4 suggest that high doses of caffeine may exacerbate psychosis, this has only recently been described for energy drinks.5 This case provides naturalistic challenge–dechallenge–rechallenge evidence that some patients with treated schizophrenia may be vulnerable to exacerbation of their illness by such products.

David B Menkes

CorrectionIncorrect statement of risk: In “Factors associated with psychiatric morbidity and hazardous alcohol use in Australian doctors” in the 2 August 2010 issue of the Journal (Med J Aust 2010; 193: 161-166), there was an error in the first paragraph on page 163. The sentence regarding solo practitioners should read: “Solo practitioners had a lower risk of psychiatric morbidity than non-solo practitioners (OR, 0.78 [95% CI, 0.61–0.99]).” The html and pdf versions of this article were corrected on 10 November 2010.

Louise M Nash · Michele G Daly · Patrick J Kelly · Elizabeth H van Ekert · Garry Walter · Merrilyn Walton · Simon M Willcock · Chris C Tennant

To the Editor: Significant morbidity and mortality are associated with excessive alcohol use, which, for Aboriginal Australians, generally occurs within a context of disadvantage. During 2007–2009, we assessed cognitive and psychological factors (using CogState1 and Strong Souls2 [CogState Ltd, Melbourne, Vic]) of 21 men and 11 women on admission to a 2-month Aboriginal residential treatment program in the Northern Territory. Participants’ mean age was 32 years (SD, 8.7 years) and the mean length of time for which they had used alcohol was 13.3 years (SD, 7.7 years). To determine the effect of age, number of years of drinking and other factors on continued alcohol use, we reinterviewed and reassessed participants in their home community with the same cognitive and psychological measures used at the initial assessment after a mean period of 11 months (SD, 4.4 months). At both baseline and follow-up, the number of participants for whom data were available varied for some characteristics. The Human Research Ethics Committee of the Northern Territory Department of Health and Community Services and Menzies School of Health Research (including the Aboriginal Ethics Sub Committee) approved the study. At baseline, 14 of 23 alcohol users reported drinking every day or most days, and 26 of 31 drank more than 10 standard drinks on each occasion. At follow-up in the community, 23 had resumed drinking at the same level, and nine had reduced their use (six had stopped using alcohol, and three had resumed drinking at lower levels). Compared with users who reduced their alcohol intake, users who did not showed poorer paired associate learning at the time of admission for treatment, and poorer performance at follow-up in visual attention, learning and executive function, visual learning and recall, and paired associate learning tasks (Box). This suggests that while subtle cognitive impairment may be a risk factor for continued heavy alcohol use after treatment, heavy alcohol use is also a likely cause of additional cognitive deficits.3 While reduced alcohol use may be associated with improvements in cognitive function, continued use may lead to further cognitive decline. Alcohol users who resumed drinking at the same level were significantly more likely to experience the psychological symptom “worry” after treatment (4/6; Fisher exact test, P < 0.05) than were users who reduced their alcohol use (0/6), which suggests that alcohol may have been used for self-medication or that excessive alcohol use may mask underlying psychological problems. Interestingly, a greater proportion of alcohol users who resumed drinking at the same level (10/16) were also using cannabis at follow-up, compared with those who reduced their use (1/9; Fisher exact test, P < 0.05). Cannabis use has been independently associated with psychological symptoms in other Australian studies, but with no impact on cognition.2,4 Our data indicate that there is a need to treat mental health problems concurrently with alcohol misuse problems among alcohol users undergoing treatment. Alcohol users who resumed drinking at the same level were less likely to return to remote communities with restricted alcohol availability (11/23), compared with those who reduced their alcohol use (9/9; Fisher exact test, P < 0.01), lending some support to the effectiveness of alcohol restrictions. Overall, our data show that cognitive problems and alcohol availability may be underlying factors in ongoing alcohol misuse by Aboriginal Australians. Charactersitics of alcohol users who resumed drinking at the same level and those who reduced their alcohol use after a 2-month residential treatment program, at baseline and at follow-up (n = 32) Characteristic Unchanged alcohol use, median Reduced alcohol use, median Z Significance No. of alcohol users 23 9 Age at baseline, years 31.3 29.0 − 0.15 ns Years of drinking, at baseline 13.0 11.6 − 0.59 ns Visual attention, speed (log transformed)* Baseline 2.81 2.76 − 1.67 ns Follow-up 2.79 2.71 − 2.10 P = 0.04 Working memory, accuracy (arcsine transformed)† Baseline 0.70 0.70 − 0.19 ns Follow-up 0.80 0.74 − 0.53 ns Psychomotor speed, moves per second† Baseline 0.77 0.95 − 0.35 ns Follow-up 1.17 1.37 − 0.75 ns Learning and executive function, moves per second† Baseline 0.44 0.47 − 0.39 ns Follow-up 0.58 0.76 − 2.32 P = 0.02 Visual learning and recall, moves per second† Baseline 0.48 0.46 − 0.21 ns Follow-up 0.73 0.84 − 2.20 P = 0.03 Paired associate learning, duration (seconds)* Baseline 307.81 214.11 − 2.52 P = 0.01 Follow-up 286.51 168.48 − 2.67 P = 0.008 ns = not significant; P > 0.07. * Higher values indicate poorer performance. † Higher values indicate better performance.

Kylie M Dingwall · Paul Maruff · Sheree Cairney

To the Editor: In response to Hall and colleagues,1 the Royal Australasian College of Surgeons supports any measures that have been proven to successfully reduce death and injury in young drivers. Raising the minimum legal drinking age (MLDA) to 21 years has been shown to significantly decrease road crash deaths in the United States.1 The College agrees with these authors that there would be major political obstacles and very little public support in Australia to increasing the MLDA; however, should the politicians and the public see first hand the devastating effects of alcohol on young people that our surgeons see on an all-too-regular basis, the mindset might change significantly. Hall and colleagues state other ways that we can achieve further reductions in road crash deaths — extending the zero-tolerance laws for young drivers until age 22 years, as it is in Victoria, or until 25 years for even further reductions.1 The College certainly supports this, particularly as evidence is building that the physical maturation of the part of the human brain that assesses risk and controls impulsive behaviour is not complete until age 25 years in men.2-4 The Trauma Committee is most concerned about alcohol-related trauma and will explore this issue at the annual Trauma Committee workshop, during the College’s Trauma Week. The workshop, entitled “Alcohol and injury”, will be held at the College in Melbourne on 18 November 2010.

Daryl R Wall

Herbert Gibson, well known in Victoria for his dedicated work on HIV/AIDS, bloodborne viruses, and drugs and alcohol, died suddenly on 5 June 2010 at the age of 64. Born on 19 August 1945 in Bendigo, Victoria, Herbert studied medicine at Monash University, graduating in 1970. He did his residency at Bendigo Base Hospital and the Lakeside Psychiatric Hospital, Ballarat. In 1973, he helped found the Middle Park Clinic in Melbourne, where he was at the centre of medical care and studies to combat HIV/AIDS. His work included lecturing on sexually transmitted diseases and bloodborne viruses for Monash University, the Victorian Health Promotion Commission, the Royal Australian College of General Practitioners and the Alfred Hospital, where he was also Honorary Clinical Assistant at the Special Microbiology Unit (HIV/AIDS). In addition, he undertook honorary palliative care work for a number of Melbourne’s medical facilities. In 1994, Herbert moved back to his home town of Bendigo to care for his elderly mother. He became Senior Psychiatric Medical Officer with the Bendigo Health Care Group, and also worked for the Rural Health General Practice division of Monash University in Bendigo. He was an Outreach Rural Mental Health visiting consultant and Crisis Assessment Team clinician throughout the extensive Loddon/Campaspe region of Victoria. The stress of long hours and distance travel eventually took its toll, and family-inherited bipolar disorder and diabetes began to wear him down. In 2007, he retired from practice and moved to Sydney, where his health greatly improved. Apart from his dedication to medical care for the underprivileged and marginalised, Herbert’s passions in life were reading European history and tracking down rare stamps for his collection, especially stamps of Imperial Russia and the early Soviet Union. He also enjoyed painting with watercolours and relaxing with his music collection of Wagner, Mozart and Shostakovich. A suspected minor stroke/brain haemorrhage in 2010 saw him admitted to St Vincent’s Hospital, Sydney. He was transferred to the nearby Sacred Heart Hospice, where he died within a few days. A month later, a celebration of Herbert’s life was held in Melbourne, where some 70 former patients, staff, colleagues and friends gathered to remember a convivial, compassionate medic, a brilliant diagnostician and generous associate who enjoyed both solitude and good company.

Edward Underwood

Objectives: To determine the prevalence of occult brain abnormalities in magnetic resonance imaging of active amphetamine users.Design, setting and participants: Prospective convenience study in a tertiary hospital emergency department (ED). Patients presenting to the ED for an amphetamine-related reason were eligible for inclusion. We collected demographic data, drug use data, and performed a mini-mental state examination (MMSE).Main outcome measures: The proportion of patients with an abnormality on their MRI scan.Results: Of 38 patients enrolled, 30 had MRI scans. Nineteen were male and their mean age was 26.7 ± 5.4 years (range 19–41 years). The mean age of first amphetamine use was 18 years (range 13–26 years). Sixteen patients used crystal methamphetamine (mean amount 2.5 g/week), nine used amphetamine (“speed”) (mean amount 2.9 g/week), and 23 used ecstasy (mean amount 2.3 tablets/week). Marijuana was smoked by 26 (mean amount 5.9 g/week), and 28 drank alcohol (mean amount 207 g/week). The median MMSE score was 27/30 (interquartile range, 26–29). Abnormalities on brain MRI scans were identified in six patients, most commonly an unidentified bright object (n = 4).Conclusion: In this pilot study of brain MRI of young people attending the ED with an amphetamine-related presentation, one in five had an occult brain lesion. While the significance of this is uncertain, it is congruent with evidence that amphetamines cause brain injury.

Daniel M Fatovich MB BS, FACEM · David L McCoubrie MB BS, FACEM · Swithin J Song MB BS, FRANZCR · David M Rosen MB BS, FRACP, PhD · Nick D Lawn MB ChB, FRACP · Frank F Daly MB BS, FACEM

Objective: Design, setting and participants: Descriptive study of alcohol consumption in the NT population, based on sales data and self-report surveys, and alcohol-attributable deaths and hospitalisations among people in the NT in the 2004–05 and 2005–06 financial years using population alcohol-attributable fractions specific to the NT.Main outcome measures: Per capita consumption of pure alcohol, self-reported level of consumption, and age-standardised rates of death and hospitalisation attributable to alcohol.Results: Apparent per capita consumption of pure alcohol for both Aboriginal and non-Aboriginal populations in the NT has been about 14 litres or more per year for many years, about 50% higher than for Australia as a whole. We estimated that there were 120 and 119 alcohol-attributable deaths in the NT in 2004–05 and 2005–06, respectively, at corresponding age-standardised rates of 7.2 and 7.8 per 10 000 adult population. Alcohol-attributable deaths occur in the NT at about 3.5 times the rate they do in Australia generally; rates in non-Aboriginal people were about double the national rate, while they were 9–10 times higher in Aboriginal people. There were 2319 and 2544 alcohol-attributable hospitalisations in the NT in 2004–05 and 2005–06, respectively, at corresponding rates of 146.6 and 157.7 per 10 000 population (more than twice the national rate).Conclusion: In recent years, alcohol consumption and consequent alcohol-attributable deaths and hospitalisations for both Aboriginal and non-Aboriginal people in the NT have occurred at levels far higher than elsewhere in Australia.

Steven J Skov MB BS, FAFPHM, MPH · Tanya N Chikritzhs BA(Hons), PostGradDip(Epi · Shu Q Li BM, BN, MPH · Sabine Pircher BNutrDiet, MPH · Steven Whetton BEc(Hons), MSc(Economics)

Objective: To investigate morbidity related to misuse of over-the-counter (OTC) codeine–ibuprofen analgesics.Design and setting: Prospective case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008.Main outcome measures: Morbidity associated with codeine–ibuprofen misuse.Results: Twenty-seven patients with serious morbidity were included, mainly with gastrointestinal haemorrhage and opioid dependence. The patients were taking mean daily doses of 435–602 mg of codeine phosphate and 6800–9400 mg ibuprofen. Most patients had no previous history of substance use disorder. The main treatment was opioid substitution treatment with buprenorphine–naloxone or methadone.Conclusions: Although codeine can be considered a relatively weak opioid analgesic, it is nevertheless addictive, and the significant morbidity and specific patient characteristics associated with overuse of codeine–ibuprofen analgesics support further awareness, investigation and monitoring of OTC codeine–ibuprofen analgesic use.

Matthew Y Frei MB BS, FAChAM · Suzanne Nielsen BPharm, PhD, MPS · Malcolm D H Dobbin PhD, MB BS, FAFPHM · Claire L Tobin RN, MPH

Incorrect statement of risk: In “Factors associated with psychiatric morbidity and hazardous alcohol use in Australian doctors” in the 2 August 2010 issue of the Journal (Med J Aust 2010; 193: 161-166), there was an error in the last paragraph of the Results section (page 163). The wording of the last sentence of the paragraph should be: “Doctors were at less risk of hazardous alcohol use if they: trained overseas rather than in Australia (OR, 0.56 [95% CI, 0.39–0.81); worked more than 60 hours a week compared with less than 40 hours a week (OR, 0.67 [95% CI, 0.45–0.99]); and had not taken a holiday in more than a year (OR, 0.63 [95% CI, 0.43–0.93]).”

Louise M Nash · Michele G Daly · Patrick J Kelly · Elizabeth H van Ekert · Garry Walter · Merrilyn Walton · Simon M Willcock · Chris C Tennant

Objective: To identify factors associated with psychiatric morbidity and hazardous alcohol use in Australian doctors.Design, setting and participants: Cross-sectional postal survey of 2999 doctors (including all major specialty groups, trainees and general practitioners) insured with an Australian medical insurance company. The potential for psychiatric morbidity was measured by the General Health Questionnaire (GHQ), and the potential for hazardous alcohol use by the Alcohol Use Disorders Identification Test (AUDIT). The survey was conducted in 2007.Main outcome measures: Demographic, work-related and personality factors associated with a GHQ score > 4 and an AUDIT score ≥ 8.Results: Factors significantly associated with psychiatric morbidity in doctors were: having a current medicolegal matter, not taking a holiday in the previous year, working long hours, type of specialty, and having personality traits of neuroticism and introversion. Factors significantly associated with potentially hazardous alcohol use were being male, being Australian-trained, being between 40 and 49 years of age, having personality traits of neuroticism and extroversion, failing to meet Continuing Medical Education requirements, and being a solo practitioner.Conclusions: The mental health of medical practitioners is crucial to the quality of care their patients receive. Doctors should reflect on their hours of work and need for holidays. Involvement with medicolegal processes, such as lawsuits, complaints and inquiries, is a stressful part of medical practice today. Doctors need to be educated about these processes and understand how the experience may affect their health, work and loved ones.

Louise M Nash MB BS(Hons), BA, FRANZCP · Michele G Daly BSc(Hons), MSc · Patrick J Kelly BMath(Hons), PhD · Elizabeth H van Ekert BADipEd, MMedHum · Garry Walter MB BS, PhD, FRANZCP · Merrilyn Walton BA, MSW, PhD · Simon M Willcock MB BS, PhD, FRACGP · Chris C Tennant MD, MPH, FRANZCP

Objective: To assess women’s compliance with different Australian guidelines on alcohol intake during pregnancy and examine factors that might influence compliance.Design, setting and participants: We analysed prospective, population-based data on women aged 22–33 years who were pregnant before October 2001, when guidelines recommended zero alcohol (n = 419), or were first pregnant after October 2001, when guidelines recommended low alcohol intake (n = 829). Data were obtained from surveys conducted in 1996, 2000, 2003 and 2006 as part of the Australian Longitudinal Study on Women’s Health.Main outcome measures: Relative risks (RRs) for zero alcohol intake, low alcohol intake and compliance with alcohol guidelines, estimated by a modified Poisson regression model with robust error variance.Results: About 80% of women consumed alcohol during pregnancy under zero and low alcohol guidelines. Compliance with zero alcohol guidelines or low alcohol guidelines (up to two drinks per day and less than seven drinks per week) was the same for women who were pregnant before October 2001 and women who were first pregnant after October 2001 (20% v 17% for compliance with zero alcohol guidelines, P > 0.01; 75% v 80% for compliance with low alcohol guidelines, P > 0.01). Over 90% of women drank alcohol before pregnancy and prior alcohol intake had a strong effect on alcohol intake during pregnancy, even at low levels (RR for zero alcohol, 0.21 [95% CI, 0.16–0.28]; RR for low alcohol, 0.91 [95% CI, 0.86–0.96]). RR for compliance with guidelines was 3.54 (95% CI, 2.85–4.40) for women who were pregnant while low alcohol intake was recommended, compared with those who were pregnant while zero alcohol guidelines were in place.Conclusion: The October 2001 change in alcohol guidelines does not appear to have changed behaviour. Risks associated with different levels of alcohol intake during pregnancy need to be clearly established and communicated.

Jennifer R Powers BSc, MMedStat · Deborah J Loxton BPsych(Hons), PhD · Lucy A Burns MPH, PhD, GradCertHlthPol · Anthony Shakeshaft BA, MA, PhD · Elizabeth J Elliott MD, MPhil, FRACP · Adrian J Dunlop MB BS, PhD, FAChAM

To the Editor: We present a case of fatal cocaine overdose in which the drug was contaminated with levamisole, a therapeutic agent known to cause reversible agranulocytosis. The deceased, a previously well woman in her early 20s, was found dead in circumstances suspicious of a drug overdose. The death was reported to the coroner and the autopsy findings were unremarkable, with no evidence of injury or significant natural disease processes. Toxicological sampling of blood revealed a cocaine level in the blood of 4.9 mg/L, as well as the cocaine metabolite benzoylecgonine at a level of 3.4 mg/L. These are lethal levels for cocaine and benzoylecgonine.1 Cocaine was also detected in a nasal swab, and levamisole was detected in the nasal swab and in the blood, as well as in a quantity of white powder found near the woman’s body. The cause of death was given as cocaine toxicity. Illicit cocaine in Australia is generally diluted (“cut”) with a range of innocuous substances, including fructose and sucrose, and less commonly with other drugs, such as lignocaine.2 In this case, levamisole was detected as a contaminant. Levamisole is primarily used as a veterinary anthelmintic, and used uncommonly in humans for rheumatoid arthritis, and as adjuvant therapy to fluorouracil in the treatment of a variety of cancers.3,4 Agranulocytosis is a significant side effect of levamisole, and this has limited its use in humans. The clinical presentation of agranulocytosis is protean, presenting with a spectrum of abnormalities, ranging from a flu-like illness to leukopenia with a potentially fatal outcome.3-5 The mechanism whereby levamisole induces agranulocytosis is unknown, although a strong link with the human leukocyte antigen HLA-B27 and rheumatoid factor positivity suggests a likely genetic predisposition.4 Recent reports from the United States and Canada have highlighted the presence of levamisole in seized illicit cocaine entering these countries, with up to 69% of seized cocaine lots containing levamisole. There has been a subsequent clustering of fatal and nonfatal cases of agranulocytosis in a number of disparate locations.3-5 The reason for contaminating cocaine with levamisole is unknown, although there are indications that levamisole may promote the effects of cocaine by interfering with its reuptake at a synaptic level.4 Although there was no evidence of agranulocytosis in the present case, we highlight the apparent recent appearance of this contaminant in the cocaine supply in Australia, because it has the potential to induce reversible agranulocytosis in people not otherwise obviously at risk for this condition.

Johan A Duflou · Issabella G Brouwer · Shane Darke

Objective: To conduct a systematic review of randomised trials of web-based interventions for problematic substance use by adolescents and young adults.Data sources: An extensive search conducted in February 2009 of computer databases (MEDLINE, PsycINFO, Current Contents) and manual searches of key references.Study selection: Randomised comparisons of fully automated web-based interventions specifically targeting adolescents and young adults (ie, typically school or tertiary students, ≤ 25 years old) versus other interventions.Data synthesis: 16 relevant studies were identified, and data were extracted from 13 of the 14 reporting on alcohol use by young adults. The alcohol interventions had a small effect overall (d = − 0.22) and for specific outcomes (level of alcohol consumption, d = − 0.12; binge or heavy drinking frequency, d = − 0.35; alcohol-related social problems, d = − 0.57). The interventions were not effective (d = − 0.001) in preventing subsequent development of alcohol-related problems among people who were non-drinkers at baseline. Due to methodological differences, data from the two studies reporting on tobacco interventions among adolescents were not combined.Conclusions: Based on findings largely from tertiary students, web interventions targeting alcohol-related problems have an effect about equivalent to brief in-person interventions, but with the advantage that they can be delivered to a far larger proportion of the target population. Web-based interventions to prevent the development of alcohol-related problems in those who do not currently drink appear to have minimal impact. There are currently insufficient data to assess the effectiveness of web-based interventions for tobacco use by adolescents.

Robert J Tait BSc(Hons), PhD · Helen Christensen PhD