Raimondo Bruno

Comparison of unlimited numbers of rapid transcranial magnetic stimulation (rTMS) and ECT treatment sessions in major depressive episode

Repetitive transcranial magnetic stimulation (rTMS) is a new technology which holds promise as a treatment of psychiatric disorders. Most work to date has been on depression. Superiority to placebo has been indicated in three small blind studies. We compared the antidepressant effects of rTMS and ECT in 32 patients suffering major depressive episode (MDE) who had failed to respond to at least one course of medication. There was no limit to the number of treatment sessions which could be given and treatment was continued until remission occurred or response plateaued. A significant main effect for treatment type was found [Pillai trace = 0.248, F(3,28) = 3.076, p = 0.044; power = 0.656], reflecting an advantage for ECT patients on measures of depression overall, however, rTMS produced comparable results on a number of measures. Blind raters using the 17-item Hamilton Depression Rating Scale (HDRS) found the rate of remission (HDRS = ? 8) was the same (68.8%), and the percentage improvement over the course of treatment of 55.6% (rTMS) and 66.4% (ECT), while favouring ECT, was not significantly different. Significant differences were shown (p & 0.03) in percentage improvement on Beck Depression Inventory ratings (rTMS, 45.5%; ECT, 69.1%), but not for improvement in Visual Analogue ratings of mood (rTMS 42.3%; ECT, 57%). rTMS has antidepressant effects of useful proportions and further studies are indicated.

Refining the estimation of illicit drug consumptions from wastewater analysis: Co-analysis of prescription pharmaceuticals and uncertainty assessment

Wastewater analysis is a promising monitoring tool to estimate illicit drug consumption at the community level. The advantage of this technique over traditional surveys and other surveillance methods has been emphasized in recent studies. However, there are methodological challenges that can affect reliability. The objectives of this study were to systematically reduce and assess uncertainties associated with sampling (through a stringent optimization of the sampling method) and the back calculation of per capita drug consumption (through a refined estimation of the number of people actively contributing to the wastewater in a given period). We applied continuous flow-proportional sampling to ensure the collection of representative raw wastewater samples. Residues of illicit drugs, opioids, prescription pharmaceuticals and one artificial sweetener were analyzed by liquid chromatography coupled with tandem mass spectrometry. A parameter estimating the number of people actively contributing to wastewater over a given period was calculated from the measured loads of prescription pharmaceuticals, their annual consumption and relative excretion data. For the calculation of substance loads in sewage, uncertainties were propagated considering five individual components: sampling, chemical analysis, flow measurements, excretion rates and the number of people contributing to the wastewater. The daily consumption per 1000 inhabitants was estimated to be almost 1000 mg for cannabis and several hundred mg for cocaine, methamphetamine and ecstasy. With the best sampling practice and current chemical analysis, we calculated the remaining uncertainty to be in the range of 20-30% (relative standard deviation, RSD) for the estimation of consumed drug masses in the catchment; RSDs for the per capita consumption were lower (14-24%), as one of the biggest uncertainty components (i.e. error in flow measurements) cancels out in the proposed method for the estimation of the number of people contributing to the daily wastewater volume. In this study, we provide methodological improvements that substantially enhance the reliability of the estimation method--a prerequisite for the application of this technique to meaningfully assess changes in drug consumption and the success of drug intervention strategies in future studies.

Prescription of opioid analgesics and related harms in Australia.

Objective: To document trends in: (i) prescribing of morphine and oxycodone; (ii) hospital separations for overdose; (iii) presentations for treatment of problems associated with these drugs; and (iv) oxycodone‐related mortality data in Australia.

The epidemiology of methamphetamine use and harm in Australia

INTRODUCTION AND AIMS There has been considerable media attention recently upon possible increases in methamphetamine use in Australia. Much of this debate has focused upon extreme cases of problematic crystal methamphetamine use, without reference to the broader population context. This paper provides data on methamphetamine use in Australia, and documents trends in methamphetamine-related harms. DESIGN AND METHODS Data used were from: (1) Australian Customs Service drug detections; (2) Australian Crime Commission drug seizure, arrest and clandestine laboratory detections data; (3) National Drug Strategy Household Survey (NDSHS) and Australian Secondary Student Alcohol and Drug Survey (ASSADS); (4) data from the Illicit Drug Reporting System (IDRS) and Ecstasy and related Drug Reporting System (EDRS); and (5) data from NSW Emergency Department Information System, National Hospital Morbidity Database and Australian Bureau of Statistics causes of death databases. RESULTS There appears to have been an increase in both importation and local manufacture of meth/amphetamine. Population data show that meth/amphetamine use remains low and stable. However, clear increases in crystal methamphetamine use have occurred among sentinel groups of regular drug users. Frequent crystal use among regular injecting drug users is associated with earlier initiation to injecting, greater injection risk behaviours and more extensive criminal activity. In recent years, indicators of meth/amphetamine-related harm have stabilised, following steady increases in earlier years. DISCUSSION AND CONCLUSIONS Some methamphetamine users experience significant problems related to their use; harms are particularly prevalent among regular IDU. Methamphetamine users, however, are a diverse group, and strategies need to be appropriately targeted towards different kinds of users.

Trends in morphine prescriptions, illicit morphine use and associated harms among regular injecting drug users in Australia

This paper examines population trends in morphine prescriptions in Australia, and contrasts them with findings from annual surveys with regular injecting drug users (IDU). Data on morphine prescriptions from 1995 to 2003 were obtained from the Drug Monitoring System (DRUMS) run by the Australian Government Department of Health and Ageing. Data collected from regular IDU as part of the Australian Illicit Drug Reporting System (IDRS) were analysed (2001 - 2004). The rate of morphine prescription per person aged 15 - 54 years increased by 89% across Australia between 1995 and 2003 (from 46.3 to 85.9 mg per person). Almost half (46%) of IDU surveyed in 2004 reported illicit morphine use, with the highest rates in jurisdictions where heroin was less available. Recent morphine injectors were significantly more likely to be male, unemployed, out of treatment and homeless in comparison to IDU who had not injected morphine. They were also more likely to have injected other pharmaceutical drugs and to report injection related problems. Among those who had injected morphine recently, the most commonly reported injecting harms were morphine dependence (38%), difficulty finding veins into which to inject (36%) and scarring or bruising (27%). Morphine use and injection is a common practice among regular IDU in Australia. In some cases, morphine may be a substitute for illicit heroin; in others, it may be being used to treat heroin dependence where other pharmacotherapies, such as methadone and buprenorphine, are perceived as being unavailable or undesirable by IDU. Morphine injection appears to be associated with polydrug use, and with it, a range of problems related to drug injection. Further research is required to monitor and reduce morphine diversion and related harms by such polydrug injectors.

The impact of alcohol and energy drink consumption on intoxication and risk-taking behavior

BACKGROUND It has been argued that consuming alcohol mixed with energy drinks (AmED) causes a subjective underestimation of intoxication and an increased level of risk-taking behavior. To date, however, there is mixed support for AmED-induced reductions in perceived intoxication, and no objective assessment of risk-taking following AmED consumption. Consequently, the present study aimed to determine the effect of alcohol and energy drink (ED) consumption on subjective measures of intoxication and objective measures of risk-taking. METHODS Using a placebo-controlled, single-blind, cross-over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 0.5 g/kg alcohol, 3.57 ml/kg ED, AmED, and a placebo beverage. Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk-taking was measured using the Balloon Analogue Risk Task (BART). RESULTS Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects. However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions. There was no independent effect of alcohol, or interactive effect with ED, on the BART. A significant, yet small magnitude, increase in risk-taking was evident in active relative to placebo ED conditions. CONCLUSIONS The interactive effect of AmED appears restricted to perceived stimulation, with alcohol-induced increases in subjective intoxication occurring regardless of presence or absence of ED. Engagement in risk-taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk-taking. Further research assessing the dose-dependent effects of AmED on objectively measured risk-taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses.

The Pain and Opioids IN Treatment study: characteristics of a cohort using opioids to manage chronic non-cancer pain

Abstract There has been a recent increase in public and professional concern about the prescription of strong prescription opioids for pain. Despite this concern, research to date has been limited because of a number of factors such as small sample sizes, exclusion of people with complex comorbidities, and studies of short duration. The Pain and Opioids IN Treatment is a 2-year prospective cohort study of 1500 people prescribed with pharmaceutical opioids for their chronic pain. This article provides an overview of the demographic and clinical characteristics of the cohort using the baseline data of 1514 community-based people across Australia. Participants had been in pain for a period of 10 years and had been on prescription opioids for approximately 4 years. One in 10 was on a daily morphine equivalent dose of ≥200 mg. Employment and income levels were low, and two-thirds of the sample reported that their pain had impacted on their employment status. Approximately 50% screened positive for current moderate-to-severe depression, and 1 in 5 had made a lifetime suicide attempt. There were a number of age-related differences. The younger groups experienced higher levels of pain and pain interference, more mental health and substance use issues, and barriers to treatment, compared with the older group. This study found that the people who have been prescribed strong opioids for chronic pain have very complex demographic and clinical profiles. Major age-related differences in the experiences of pain, coping, mental health, and substance use suggest the necessity of differential approaches to treatment.

Alcohol Use and Risk Taking Among Regular Ecstasy Users

We examine alcohol use in conjunction with ecstasy use and risk-taking behaviors among regular ecstasy users in every capital city in Australia. Data on drug use and risks were collected in 2004 from a national sample of 852 regular ecstasy users (persons who had used ecstasy at least monthly in the preceding 6 months). Users were grouped according to their typical alcohol use when using ecstasy: no use, consumption of between one and five standard drinks, and consumption of more than five drinks (“binge” alcohol use). The sample was young, well educated, and mainly working or studying. Approximately two thirds (65%) of the regular ecstasy users reported drinking alcohol when taking ecstasy. Of these, 69% reported usually consuming more than five standard drinks. Those who did not drink alcohol were more disadvantaged, with greater levels of unemployment, less education, higher rates of drug user treatment, and prison history. They were also more likely than those who drank alcohol when using ecstasy to be drug injectors and to be hepatitis C positive. Excluding alcohol, drug use patterns were similar between groups, although the no alcohol group used cannabis and methamphetamine more frequently. Binge drinkers were more likely to report having had three or more sexual partners in the past 6 months and were less likely to report having safe sex with casual partners while under the influence of drugs. Despite some evidence that the no alcohol group were more entrenched drug users, those who typically drank alcohol when taking ecstasy were as likely to report risks and problems associated with their drug use. It appears that regular ecstasy users who binge drink are placing themselves at increased sexual risk when under the influence of drugs. Safe sex messages should address the sexual risk associated with substance use and should be tailored to reducing alcohol consumption, particularly targeting “heavy” alcohol users. The studys limitations are noted.

Estimating daily and diurnal variations of illicit drug use in Hong Kong: a pilot study of using wastewater analysis in an Asian metropolitan city.

The measurement of illicit drug metabolites in raw wastewater is increasingly being adopted as an approach to objectively monitor population-level drug use, and is an effective complement to traditional epidemiological methods. As such, it has been widely applied in western countries. In this study, we utilised this approach to assess drug use patterns over nine days during April 2011 in Hong Kong. Raw wastewater samples were collected from the largest wastewater treatment plant serving a community of approximately 3.5 million people and analysed for excreted drug residues including cocaine, ketamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and key metabolites using liquid chromatography coupled with tandem mass spectrometry. The overall drug use pattern determined by wastewater analysis was consistent with that have seen amongst people coming into contact with services in relation to substance use; among our target drugs, ketamine (estimated consumption: 1400-1600 mg/day/1000 people) was the predominant drug followed by methamphetamine (180-200 mg/day/1000 people), cocaine (160-180 mg/day/1000 people) and MDMA (not detected). The levels of these drugs were relatively steady throughout the monitoring period. Analysing samples at higher temporal resolution provided data on diurnal variations of drug residue loads. Elevated ratios of cocaine to benzoylecgonine were identified unexpectedly in three samples during the evening and night, providing evidence for potential dumping events of cocaine. This study provides the first application of wastewater analysis to quantitatively evaluate daily drug use in an Asian metropolitan community. Our data reinforces the benefit of wastewater monitoring to health and law enforcement authorities for strategic planning and evaluation of drug intervention strategies.

An analysis of ethical issues in using wastewater analysis to monitor illicit drug use

AIMS To discuss ethical issues that may arise in using WWA to monitor illicit drug use in the general population and in entertainment precincts, prisons, schools and work-places. METHOD Review current applications of WWA and identify ethical and social issues that may be raised with current and projected future uses of this method. RESULTS Wastewater analysis (WWA) of drug residues is a promising method of monitoring illicit drug use that may overcome some limitations of other monitoring methods. When used for monitoring purposes in large populations, WWA does not raise major ethical concerns because individuals are not identified and the prospects of harming residents of catchment areas are remote. When WWA is used in smaller catchment areas (entertainment venues, prisons, schools or work-places) their results could, possibly, indirectly affect the occupants adversely. Researchers will need to take care in reporting their results to reduce media misreporting. Fears about possible use of WWA for mass individual surveillance by drug law enforcement officials are unlikely to be realized, but will need to be addressed because they may affect public support adversely for this type of research. CONCLUSIONS Using wastewater analysis to monitor illicit drug use in large populations does not raise major ethical concerns, but researchers need to minimize possible adverse consequences in studying smaller populations, such as workers, prisoners and students.