Linda Gowing

The health effects of ecstasy: a literature review

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is the third most used illicit drug, after cannabis and amphetamines. There has been considerable interest in the adverse effects of use, with particular attention given to a small number of deaths related to ecstasy use, and the neurotoxic effects of MDMA. This paper reviews case reports of adverse effects attributed to ecstasy use, and the findings of animal and human studies, so as to identify the health effects of ecstasy use, and factors contributing to their occurrence. The incidence of serious acute adverse events related to ecstasy is low. It is the unpredictability of those adverse events and the risk of mortality and substantial morbidity that makes the health consequences of ecstasy significant. Hyperthermia and hyponatraemia are the most significant acute adverse effects, and can occur even when MDMA is the only drug used. Ecstasy users should be aware of the importance of controlling body temperature and fluid intake, early signs of adverse effects, and the need to seek medical assistance promptly. Neurotoxicity is potentially the most significant long-term effect of ecstasy. The clinical implications of neurotoxicity are uncertain at this time, but short-term memory impairment may be significant.

Pharmacotherapies for problematic psychostimulant use: a review of current research

This review summarizes the current status of clinical research on pharmacotherapies for problematic psychostimulant use. The use of psychostimulants, including amphetamine, cocaine and ecstasy, is increasingly a feature of Australian life as is the presentation of patients with psychostimulant disorders. A lack of experience, resources and treatment options have constrained the response of treatment services to such problems. Despite extensive research, particularly in the area of cocaine, no pharmacotherapy has been proven effective in the management of psychostimulant disorders. The harms associated with problematic psychostimulant use warrant further controlled research in innovative approaches integrated with psychosocial interventions.

A comparison of antagonist-precipitated withdrawal under anesthesia to standard inpatient withdrawal as a precursor to maintenance naltrexone treatment in heroin users: outcomes at 6 and 12 months

To compare two methods of heroin withdrawal, 51 heroin users were randomised to undergo a 1 day precipitated withdrawal procedure using naloxone under anaesthetic. About 50 participants were randomised to receive the current standard inpatient withdrawal treatment using clonidine plus symptomatic medication. Following withdrawal, both groups were offered 9 months of naltrexone treatment and supportive counselling. Outcome measures were: commencement of naltrexone, retention in treatment and heroin use at 6 and 12 months. Significantly more of the precipitated withdrawal group completed withdrawal, commenced naltrexone and stayed in treatment for the first 3 months. Overall, there was a significant reduction in both self-reported heroin use and morphine concentration in hair over the 12 month study period, with participants in the precipitated withdrawal group showing significantly lower morphine concentration at 6 months. Being younger and having a lower level of dependence were predictors of abstinence at 6 and 12 months. The advantage of precipitated withdrawal under anesthesia did not persist beyond 3 months with respect to retention in naltrexone treatment or beyond 6 months with respect to heroin use. Long-term follow-up is crucial in assessing the effects of treatment interventions for heroin dependence.

The place of detoxification in treatment of opioid dependence.

Purpose of review This review summarizes current research on the management of opioid withdrawal and considers the selection of the approach in different situations. Recent findings The recent publication of three controlled trials makes firm conclusions about the relative effectiveness of newer approaches (antagonist-induced withdrawal under anaesthesia or with minimal sedation; buprenorphine) to the management of opioid withdrawal possible. Summary Antagonist-induced withdrawal under anaesthesia should not be pursued as it has an increased risk of life-threatening adverse events and has no additional benefits relative to antagonist-induced withdrawal under minimal sedation. Antagonist-induced withdrawal with minimal sedation is feasible and may be suitable for those who intend to enter antagonist-maintenance treatment with a clear commitment to abstinence and good support. Buprenorphine is suitable for quick withdrawal, supports transition to naltrexone maintenance treatment, is safe and effective in outpatient settings and can be extended into maintenance treatment if the detoxification attempt is unsuccessful. Adrenergic agonists (clonidine and lofexidine) remain an effective option for those who do not want to use an opioid and do not intend to transfer to naltrexone maintenance treatment, with lofexidine being preferable for outpatient settings. Through appropriate choice of approach, detoxification can be a gateway to multiple, long-term treatment options.

Mitigating the risk of HIV infection with opioid substitution treatment

Injecting drug use is a major risk factor for the acquisition and transmission of the human immunodeficiency virus (HIV) and accounts for approximately 5 to 10% of all cases of HIV infection in the world. People who inject drugs are vulnerable to infection with HIV and other blood-borne viruses, predomi-nantly as a result of the collective use of injecting equipment and, to a lesser extent, of unprotected sexual behaviour.

Maintenance drugs to treat opioid dependence

A 39 year old woman started injecting heroin when she was 18 but soon found she could not control her drug intake or her life in general. At age 30, she sought help and did well with methadone treatment, taking no illicit drugs for three years. However, she then relapsed to heroin use and spent a year in prison, where she continued to inject heroin. After being released, she went to a residential rehabilitation centre. Subsequently in the community her general practitioner started her on buprenorphine. Her life became more stable. She did well with buprenorphine treatment for a few years but restarted injecting heroin after stopping buprenorphine. She restarted buprenorphine and now takes no non-prescribed medication. She works as a waitress and lives with her non-drug using partner. This article is intended for practitioners who occasionally manage patients with opioid dependence. Methadone, a mu opioid agonist, and buprenorphine, a partial agonist, are the main drug treatments for dependence on opioids (which include heroin, morphine, and oxycodone, as well as the other pharmaceutical opioids1 2) for detoxification, maintenance, and ultimately abstinence. Treatment with maintenance goals is referred to as opioid substitution treatment or opioid agonist pharmacotherapy.3 Such treatment is reserved for patients with clearly established opioid dependence and prolonged daily opioid use (by either smoking or injecting). In some countries the combination of buprenorphine and naloxone is preferred (and is now becoming available as a film taken sublingually). Prescription heroin, known in the United Kingdom as heroin assisted treatment or injectable opiate treatment, is used in some countries but is not discussed in this article.4 5 6 Naltrexone blocks the effects of heroin on the mu receptor,2 but oral naltrexone treatment has had low adherence and high discontinuity rates.7 8 Use of naltrexone in the …

A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence

INTRODUCTION AND AIMS Naltrexone implants are used to treat opioid dependence, but their safety and efficacy remain poorly understood. We systematically reviewed the literature to assess the safety and efficacy of naltrexone implants for treating opioid dependence. DESIGN AND METHODS Studies were eligible if they compared naltrexone implants with another intervention or placebo. Examined outcomes were induction to treatment, retention in treatment, opioid and non-opioid use, adverse events, non-fatal overdose and mortality. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data from randomised studies were combined using meta-analysis. Data from non-randomised studies were presented narratively. RESULTS Five randomised trials (n = 576) and four non-randomised studies (n = 8358) were eligible for review. The quality of the evidence ranged from moderate to very low. Naltrexone implants were superior to placebo implants [risk ratio (RR): 0.57; 95% confidence interval (CI) 0.48, 0.68; k = 2] and oral naltrexone (RR: 0.57; 95% CI 0.47, 0.70; k = 2) in suppressing opioid use. No difference in opioid use was observed between naltrexone implants and methadone maintenance (standardised mean difference: -0.33; 95% CI -0.93, 0.26; k = 1); however, this finding was based on low-quality evidence from one study. DISCUSSION The evidence on safety and efficacy of naltrexone implants is limited in quantity and quality, and the evidence has little clinical utility in settings where effective treatments for opioid dependence are used. CONCLUSION Better designed research is needed to establish the safety and efficacy of naltrexone implants. Until such time, their use should be limited to clinical trials. [Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.

Supplementary thiamine is still important in alcohol dependence.

AIMS To assess the effect of mandatory thiamine enrichment of wheat flour on blood thiamine levels in an alcohol-dependent population. METHODS Alcohol-dependent clients (n = 100) entering an inpatient service for the management of alcohol withdrawal had thiamine blood tests and diet interviews. Approximately half (n = 46) the alcohol-dependent participants reported taking vitamin supplements prior to admission. Standard treatment included thiamine supplementation in the form of an intramuscular injection and 100 mg tablets. If consent was gained, a second thiamine blood test was taken prior to discharge (n = 77). Control participants (n = 20) with no history of treatment for alcohol abuse had thiamine blood tests and diet interviews. RESULTS Control participants consumed significantly larger amounts of thiamine in their diet compared with alcohol-dependent participants (P < 0.0001). Alcohol-dependent participants who reported no use of vitamin supplements had significantly lower (P < 0.05) blood thiamine levels compared with controls, whereas controls and those who reported using vitamin supplements had no significant difference. No significant correlation was found between thiamine blood levels and reported levels of alcohol consumption. CONCLUSION Reduced blood levels of thiamine in people who are alcohol dependent, compared with those with no history of alcohol abuse, are likely to be because of the poor diet. Consumption of vitamin supplements appears to bring thiamine levels closer to those seen in control participants. Supplementation of dietary intake of thiamine in people who are alcohol dependent remains an important measure for the prevention of Wernicke-Korsakoffs syndrome in this population.

Heroin users in Australia: population trends.

The aim of this paper is to identify certain important population trends among heroin users in Australia for the period 1971 - 97, such as: population growth, initiation, i.e. the number who were initiated to heroin in a given year, and quitting, i.e. the number that quit using heroin. For this purpose, we summarize and extract relevant characteristics from data from National Drug Strategy Household Survey (NDSHS 1998) conducted in Australia in 1998. We devise a systematic procedure to estimate historical trends from questions concerning past events. It is observed from our findings that the size of the heroin user population in Australia is in a sharp increase, especially from the early 1980s onwards. The general trend obtained for the period 1971 - 97 is strikingly similar to that obtained by Hall et al. (2000) for the dependent heroin user population in Australia, even though their study was based on different datasets and a different methodology. In our reconstruction of the time history we also detect a levelling-off prior to 1990. Initiation is also observed to be on a sharp increase. The latter trend is accompanied by a similar trend of quitting, perhaps indicating a relatively short heroin use career. A sharp decrease in both initiation and quitting is observed after 1990. In conclusion, in the case of the trend in the population of heroin users a high rate of growth has been identified that is consistent with the existing literature. In the process, we demonstrated that even a static survey such as NDSHS 1998 can, sometimes, be used to extract historical (dynamic) trends of certain important variables.

Opioid antagonists and adrenergic agonists for the management of opioid withdrawal.

BACKGROUND Managed withdrawal, or detoxification, is not in itself a treatment for opioid dependence, but it is a required first step for many forms of longer-term treatment. It may also represent the end point of an extensive period of treatment such as methadone maintenance. As such, managed withdrawal is an essential component of an effective treatment system. This review is one of a series that aims to assess the evidence as to the effectiveness of approaches to managing opioid withdrawal. OBJECTIVES To assess the effectiveness of interventions involving the combined use of opioid antagonists an adrenergic agonists to manage the acute phase of opioid withdrawal. SEARCH STRATEGY Multiple electronic databases, including Medline, Embase, Psychlit, Australian Medical Index and Current Contents, were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conferences were handsearched. SELECTION CRITERIA Studies that were included: involved administration of an opioid antagonist in combination with an alpha2 adrenergic agonist; had modification of the signs and symptoms of withdrawal as the aim of the intervention; involved participants who had been diagnosed as primarily opioid dependent and were undergoing clinically managed withdrawal; had as their primary focus the acute phase of withdrawal; reported detail of the type and dose of drugs used and the characteristics of study participants; reported information on the nature of withdrawal symptoms experienced, the occurrence of side effects OR rates of completion of withdrawal; and were randomized or quasi-randomized controlled clinical trials or prospective controlled cohort studies comparing the combination of opioid antagonists and adrenergic antagonists with another form of treatment. (The findings of prospective single group studies or case series, and controlled studies without a comparison treatment modality were considered in the narrative component of the review without being identified as included studies). DATA COLLECTION AND ANALYSIS Potentially relevant studies were assessed for inclusion by one reviewer (LRG). Inclusion decisions were confirmed by consultation between all three reviewers. Included studies were assessed by all reviewers. One reviewer (LRG) undertook data extraction with the process confirmed by consultation between all three reviewers. Three studies compared treatment using an opioid antagonist-clonidine combination with treatment using clonidine only. This review incorporates data tables comparing maximum withdrawal scores and numbers of participants completing withdrawal for these three studies.. The capacity for data analysis is limited by differences in the assessment outcomes in the three studies and the likelihood of allocation bias in one study. Consequently, meta-analysis has not been undertaken to combine the findings of the three studies. MAIN RESULTS Three studies (four reports) met the criteria for inclusi on in analytical components of this review. Six further studies were identified that managed withdrawal using opioid antagonists in combination with adrenergic agonists, but which did not meet the inclusion criteria (four were single group studies, 2 were controlled studies but did not include a comparison treatment modality). Findings of these studies are considered in narrative components of the review. Naltrexone was the primary opioid antagonist used to induce withdrawal. The most common approach was to administer naltrexone once a day, using an initial dose of 12.5mg, usually on day one or day two of treatment. Doses of clonidine were generally in the range of 01.-0.3mg three times a day. Five studies provided treatment on an outpatient basis, but all studies provided extended care on the day naltrexone was first administered. (ABSTRACT TRUNCATED)