Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment.

AIM: In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD: Simple experiments to assess the levels of absorption by each route separately. RESULTS: Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION: Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.

Supervised Disulfiram's Superior Effectiveness in Alcoholism Treatment: Ethical, Methodological, and Psychological Aspects.

Disulfiram (DSF) causes the ALDH-mediated deterrence of alcohol consumption. We review recent meta-analyses showing the superior effectiveness of supervised disulfiram (SD) in alcoholism treatment compared with oral naltrexone or acamprosate (ACP). The success of SD is also consistent with the almost complete absence of alcoholism in Japanese homozygotes for 'inefficient' ALDH. However, SD is an underused treatment and some clinicians have ethical objections to DSF. We examine these objections and argue that they are based on a misunderstanding of how DSF works. In particular, we argue that SD is not as is often claimed a variety of aversion therapy but aids cognitive, behavioural, educational and psychosocial interventions. It has some unique features that need to be better understood if it is to be properly compared with other treatments and effectively employed to help alcoholic patients, especially those who have not responded to other evidence-based interventions.

Recent developments in naltrexone implants and depot injections for opiate abuse: the new kid on the block is approaching adulthood.

Implants and depot injections (DI) of naltrexone (NTX) have undergone considerable development since the first commercially available implants appeared in the mid-1990s. In particular, long-acting implants that can deliver relapse-preventing serum NTX levels for around six months have now been subjected to classic randomised controlled trials that have given positive and generally significant results when compared with oral NTX and placebo implants, or with standard post-detoxification care. They also provide lower serum levels that can prevent opiate overdose for several additional months and 3-year mortality rates are similar to those of methadone maintenance treatment (MMT). At least 18 months of antagonist-assisted abstinence may be desirable to normalise new, opiatefree cognitive-behavioural habits and extinguish old, maladaptive ones. We discuss ideological antagonisms between protagonists of MMT and of NTX implants, notably in Australia, but we argue that both treatments can and should co-exist. The main obstacle to the expansion of longacting implant treatment is not the lack of an evidential or theoretical base but the lack of a licensed product. NTX appears to block all opiates if serum levels are adequate and we stress its apparent lack of clinically significant hepatotoxicity. Some patients may need above-average serum levels and occasionally, habitual injectors continue to inject opiates despite experiencing no opiate effects.

Benzodiazepine maintenance in opiate substitution treatment: Good or bad? A retrospective primary care case-note review.

BACKGROUND: Co-prescribing benzodiazepines to patients in opiate substitution treatment is controversial and often alleged to increase mortality. In an inner-London general practice, patients with problematic benzodiazepine co-dependence were allowed benzodiazepine maintenance treatment (BMT) since 1994, providing an opportunity for analysis. METHOD: 1) Case-note review of all 278 opiate substitution treatment patients, accruing 1289 patient treatment years; 46% had concurrent BMT. 2) National Health Service database search for patients who died after leaving accrued a further 883 years of information; only patients who left the UK were unaccounted for (4%). Three groups were studied: 1) never obtained benzodiazepine prescription (NOB): n=80); 2) briefly/occasionally prescribed benzodiazepines (BOP): n=71; 3) BMT: n=127. OUTCOMES MEASURED: Treatment retention (months); deaths/100 patient treatment years; deaths after leaving the service/100 years of information. RESULTS: Treatment retention: NOB: 34 months; BOP: 51 months; BMT: 72 months. In-treatment mortality: NOB: 1.79/100 patient treatment years; BOP: 0.33/100 patient treatment years; BMT: 1.31/100 patient treatment years. Deaths after leaving service: NOB: 2.24/100 years of information, BOP: 0.63/100 years of information. However, mortality for previously BMT-patients increased by 450% to 5.90/100 years of information. DISCUSSION: BMT patients had longer treatment retention than NOB or BOP and lower mortality than NOB patients. It is unlikely that patients had access to prescribed benzodiazepines on leaving the service because of restrictions in the national guidelines but co-dependent patients are a high-risk group who may stand to gain most benefit from opiate substitution treatment if combined with benzodiazepine-maintenance.

Effects of anaesthetic agents in interference of naloxone-induced opiate-withdrawal are dose-dependent in opiate-dependent rats.

In opiate-dependent rats previous studies showed that anaesthetic agents, such as chloral hydrate, midazolam and ketamine interfere with naloxone-precipitated opiate withdrawal. Each anaesthetic induces a specific pattern of interference, indicating that the interference is agent-dependent. In order to further investigate these effects and highlight a potential pharmacological basis of opiate withdrawal interference through anaesthetic agents, we hypothesized that anaesthetic-mediated interference of opiate withdrawal is also dose-dependent. Three groups of rats were compared in an experimental procedure of rapid withdrawal induction by an antagonist under anaesthesia using sub-anaesthetic dosage of midazolam, ketamine or saline. We observed that sub-anaesthetic dosage of ketamine, or midazolam, interferes significantly with opiate withdrawal expression. This brings arguments in favour of a pharmacological basis underlying rapid antagonists induction in opiate dependent rats.

DSM IV axis II traits can influence compliance to treatment with oral naltrexone: a preliminary study on 30 opiate dependent patients.

For many decades, health specialists have successfully used their clinical ingenuity to increase the efficiency of opiate detoxification protocols. However, even if drop-out rate has decreased significantly in today's protocols, relapse after opiate detoxification remains a major problem. Therefore, naltrexone hydrochloride, an opiate antagonist, has been considered by many as a potential tool to support abstinence in what has been called "antagonist-assisted abstinence" (AAA). Nevertheless, while naltrexone implants are becoming more accessible, a large majority of centers still use oral naltrexone and adherence to treatment remains a major obstacle to AAA's efficiency. As the personality profile could give an insight into compliance, we investigated the relationship between personality profiles and naltrexone adherence in a cohort of 30 patients. The results indicate that the Axis II profile influences the likely pattern of oral naltrexone compliance. As clinicians need to identify opiate dependent patients who are most likely to benefit from oral naltrexone treatment, it therefore carries important implications and could lead to a better adjustment of therapeutic strategies for opiate dependent patients.

The prevalence and correlates of DSM-IV disorders in the Iraq Mental Health Survey (IMHS).

Data on the prevalence and correlates of anxiety, mood, behavioral, and substance disorders are presented from a 2007-8 national survey of the Iraq population, the Iraq Mental Health Survey (IMHS). The IMHS was carried out by the Iraq Ministry of Health in collaboration with the Iraq Ministry of Planning and the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. Interviews were administered to a probability sample of Iraqi household residents by trained lay interviewers. The WHO Composite International Diagnostic interview (CIDI) was used to assess DSM-IV disorders. The response rate was 95.2%. The estimated lifetime prevalence of any disorder was 18.8%. Cohort analysis documented significantly increasing lifetime prevalence of most disorders across generations. This was most pronounced for panic disorder and post-traumatic stress disorder, with lifetime-to-date prevalence 5.4-5.3 times as high at comparable ages in the youngest (ages 18-34) as oldest (ages 65+) cohorts. Anxiety disorders were the most common class of disorders (13.8%) and major depressive disorder (MDD) the most common disorder (7.2%). Twelve-month prevalence of any disorder was 13.6%, with 42.1% of cases classified mild, 36.0% moderate, and 21.9% serious. The disorders most often classified serious were bipolar disorder (76.9%) and substance-related disorders (54.9%). Socio-demographic correlates were generally consistent with international epidemiological surveys, with the two exceptions of no significant gender differences in mood disorders and positive correlations of anxiety and mood disorders with education. Only 2.2% of IMHS respondents reported receiving treatment for emotional problems in the 12 months before interview, including 23.7% of those with serious, 9.2% with moderate, and 5.3% with mild disorders and 0.9% of other respondents. Most healthcare treatment, which was roughly equally distributed between the general medical and specialty sectors, was of low intensity. Further analyses of barriers to seeking treatment are needed to inform government efforts to expand the detection and treatment of mental disorders.

A pharmacological modulation of opiate withdrawal using an up-/down-regulation of the noradrenergic system in opiate-dependent rats.

Chronic opioid exposure induces neuroadaptative changes in several brain systems. Amongst others the alpha adrenergic system appears to be extremely sensitive to opioid exposure and has, therefore, been proposed to play a key role in opiate withdrawal symptoms. In order to better understand the influence of the noradrenergic system in opioid withdrawal and be able to develop new therapeutic strategies, we studied the effect of pre-treatment with the alpha2 agonist (clonidine) and alpha2 antagonist (yohimbine) on naloxone-precipitated withdrawal in opiate-dependent rats. As is already known clonidine pre-treatment significantly enhances autonomic and behavioural signs of opioid withdrawal whereas yohimbine significantly attenuates them with dose-related effect. We also tested the effect of clonidine (0.1 mg/kg) during naloxone-precipitated opiate withdrawal in rats pre-treated with yohimbine (5 mg/kg) and we observed that yohimbine pre-treatment potentiates clonidine efficiency in decreasing opiate withdrawal signs. This study supports the possibility of using a noradrenergic antagonist in order to regulate adrenoreceptors chronically exposed to opioids, therefore interfering with the intensity of naloxone-precipitated opiate withdrawal and potentiating later effectiveness of noradrenergic agonists like clonidine. These results may have various applications in clinical opiate detoxification protocols and are discussed through an up-/down- regulation of adrenoreceptors.

Evaluation of cognitive functioning in 101 patients before opiate detoxification: implications in setting up therapeutic strategies.

Many studies have brought to light the facts that repeated use of drugs significantly influences one's cognitive functions, and that cognitive problems could interfere directly with one's capacity to participate in a rehabilitation program. In this research, we used the Global Deterioration Scale (GDS) to assess the cognitive status of 101 hospitalized patients in an opiate detoxification program. The results reveal that a majority of the tested patients present cognitive abnormalities to varying degrees of severity. Furthermore, these cognitive deficits are correlated with four Addiction Severity Index (ASI) scales (medical, alcohol use, drug use, and psychiatry, respectively). Considering the results, because cognition is a major issue in detoxification and rehabilitation programs, simple cognitive screening (as with the GDS) coupled with a particular interest in some aspects of a patient's anamnesis could lead to better management of opiate-dependent patients.

Ultra-rapid opiate detoxification: from clinical applications to basic science.

Rapid or ultra-rapid opiate detoxification has become increasingly popular in both private and public addiction centres. These techniques seem to facilitate the transfer of opiate-dependent patients from opiate agonist to opiate antagonist. Despite the probable complex neuropharmacological aspects involved in these procedures, their development over nearly three decades is notable for the almost complete absence of clinically relevant animal studies. This paper discusses the historical background of this occurrence, and reviews the small number of animal studies that have been conducted. Many discussions and arguments about the techniques seem to underscore their true purpose, which is not "simply to detoxify" opiate-addicted patients but to initiate long-term management with naltrexone. For this reason, it may be better to conceptualize these techniques not as "rapid detoxification" but as "rapid antagonist induction".

Últimos desarrollos en los implantes y las inyecciones depot de naltrexona; el jovencito de la escalera se está haciendo mayor / Recent developments in naltrexone implants and depot injections for opiate abuse: the new kid on the block is approaching adulthood

Los implantes y las inyecciones depot (ID) de naltrexona (NTX) han experimentado un notable desarrollo desde que aparecieron los primeros implantes comerciales a mediados de los noventa. Específicamente los implantes de larga duración, capaces de proporcionar NTX en suero con niveles capaces de prevenir las recaídas durante unos 6 meses, han sido sometidos recientemente a las clásicas pruebas con control, con resultados positivos y, generalmente, significativamente superiores a la NTX oral o implantes de placebo o tratamientos estándar post desintoxicación. Además proporcionan niveles en sangre suficientes durante varios meses más para prevenir sobredosis por opiáceos. Por otro lado los índices de mortalidad a tres años son similares a los que están en programas de mantenimiento con metadona (PMM). Por lo menos serán necesarios 18meses de abstinencia con el apoyo de antagonistas para normalizar los nuevos hábitos de comportamiento sin opiáceos y extinguir los viejos hábitos perjudiciales. Se discuten los antagonismos ideológicos que se dan, sobre todo en Australia, entre los protagonistas de PMM y los de implantes de NTX, concluyendo que ambos tipos pueden y deben coexistir. El principal obstáculo para la expansión de los tratamientos con implantes de larga duración no sería pues la falta de evidencia o de base teórica, sino la inexistencia de un fármaco con licencia. NTX parece que bloquea todos los opiáceos si sus niveles en suero son los adecuados; por otro lado debemos tener en cuenta su aparente falta de hepatotoxicidad. Algunos pacientes pueden necesitar niveles en sangre superiores y también puede ocurrir que usuarios habituales de opiáceos por vía venosa continúen inyectándose a pesar de no experimentar los efectos producidos por los opiáceos (AU)

Implants and depot injections (DI) of naltrexone (NTX) have undergone considerable development since the first commercially available implants appeared in the mid-1990s. In particular, long-acting implants that can deliver relapse-preventing serum NTX levels for around six months have now been subjected to classic randomised controlled trials that have given positive and generally significant results when compared with oral NTX and placebo implants, or with standard post-detoxification care. They also provide lower serum levels that can prevent opiate overdose for several additional months and 3-year mortality rates are similar to those of methadone maintenance treatment (MMT). At least 18 months of antagonist-assisted abstinence may be desirable to normalise new, opiate free cognitive-behavioural habits and extinguish old, maladaptive ones. We discuss ideological antagonisms between protagonists of MMT and of NTX implants, notably in Australia, but we argue that both treatment scan and should co-exist. The main obstacle to the expansion of longacting implant treatment is not the lack of an evidential or theoretical base but the lack of a licensed product. NTX appears to block all opiates if serum levels are adequate and we stress its apparent lack of clinically significant hepatotoxicity. Some patients may need above-average serum levels and occasionally, habitual injectors continue to inject opiates despite experiencing no opiate effects (AU)