Alpha(2)-adrenergic agonists for the management of opioid withdrawal
ABSTRACT Withdrawal is a necessary step prior to drug-free treatment or as the end point of long-term substitution treatment.
To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists to manage opioid withdrawal.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2008), MEDLINE (January 1966-July 2008), EMBASE (January 1985-2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles. We also contacted manufacturers in the field.
Controlled trials comparing alpha2-adrenergic agonists with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2-adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were opioid dependent.
One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors.
Twenty-four studies, involving 1631 participants, were included. Twenty-one were randomised controlled trials.Thirteen studies compared a treatment regime based on an alpha2-adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis.Alpha2-adrenergic agonists are more effective than placebo in ameliorating withdrawal, and despite higher rates of adverse effects, are associated with significantly higher rates of completion of treatment.For the comparison of alpha2-adrenergic agonist regimes with reducing doses of methadone, there were insufficient data for statistical analysis, but withdrawal intensity appears similar to or marginally greater with alpha2-adrenergic agonists, while signs and symptoms of withdrawal occur and resolve earlier. Participants stay in treatment longer with methadone. No significant difference was detected in rates of completion of withdrawal with adrenergic agonists compared to reducing doses of methadone, or clonidine compared to lofexidine. Clonidine is associated with more adverse effects than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine
Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. No significant difference in efficacy was detected for treatment regimes based on clonidine or lofexidine, and those based on reducing doses of methadone over a period of around 10 days but methadone is associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.
[Show abstract] [Hide abstract]
ABSTRACT: The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.Journal of medical toxicology: official journal of the American College of Medical Toxicology 09/2014; DOI:10.1007/s13181-014-0430-3
[Show abstract] [Hide abstract]
ABSTRACT: Withdrawal symptoms are a main reason of continuous use of opioid. This study compares the efficacy of augmentation of amantadine with clonidine in decreasing opioid withdrawal symptoms. This double-blind randomized clinical trial was carried out in the detoxification and rehabilitation inpatient ward at Razi Hospital, Tabriz, Iran during 2012. The patients were randomly assigned to receive clonidine or clonidine plus amantadine; and withdrawal symptoms were evaluated in the admission day and 24, 48, and 72 hours later. Data were analyzed using SPSS by the 2*2 repeated analyses of variances (ANOVA). From the total of 69 participants, 30 patients completed the trial in each group. The severity of symptoms, however, had an increasing trend in both groups. Analysis of variance of the symptom severity score (by The Clinical Opiate Withdrawal Scale) revealed a significant group-time interaction, and the patients who were receiving amantadine experienced milder symptoms. Treatment of opioid withdrawal symptoms with amantadine and clonidine would result in a better outcome compared with clonidine alone.
[Show abstract] [Hide abstract]
ABSTRACT: Introduction: Substance misuse disorder (DSM-5) remains a major health challenge. Harm reduction is the initial treatment goal, by reducing or eliminating non-prescribed drug use. Eventual abstinence is the ultimate harm reduction goal. However the scope for evidence-based pharmacological interventions remains limited.Areas covered: The paper takes a pragmatic clinical approach to existing and developing pharmacotherapies for substance misuse. Dependence may be characterised as a cycle with three stages: binge/intoxication, withdrawal/negative affect and preoccupation/anticipation (craving). Each of these stages may be the focus of pharmacotherapeutic intervention, and current literature is discussed which is of relevance to the practising clinician. Dependence on opiates, stimulants, cannabis and prescribed medications including benzodiazepines and the current treatments are addressed.Expert opinion: Possible pharmacotherapies of the future include anti-craving medications, which are still incompletely understood. Other developments include ultra-long-acting formulations, some of which have already been produced and are being studied or are in early clinical practice. A completely new line of investigation has been drug ‘vaccines’, whereby the body is stimulated to produce antibodies to, for example, cocaine and nicotine. Despite a number of evidence-based strategies for the treatment of substance misuse disorder, the range of licensed pharmacological treatment choices nevertheless remains narrow.Expert Opinion on Pharmacotherapy 11/2014; 16(3). DOI:10.1517/14656566.2015.983472 · 3.09 Impact Factor