Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown.

BACKGROUND: Temporary shelters were established for street-based people during the national level 5 coronavirus disease 2019 (COVID-19) lockdown. However, street-based substance users' need to access substances was not addressed, resulting in large numbers of people experiencing withdrawal. The Community Oriented Substance Use Programme (COSUP) in Tshwane provided methadone to manage opioid withdrawal. METHODS: A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020. RESULTS: The final analysis included 495 participants, of which 64 (12.9%) were initiated on 20 mg - 30 mg of methadone, 397 (80.2%) on 40 mg - 50 mg, and 34 (6.9%) on 60 mg - 70 mg. A total of 194 (39.2%) participants continued their initiation dose for 1-2 months, after which 126 (64.9%) had their doses increased, and 68 (35.1%) had their doses decreased. Approximately 12 (2.4%) participants were weaned off methadone after 1-3 months and 46 (9.3%) after 4-6 months. In all, 100 (20.2%) participants left the shelter prematurely and did not continue with methadone. A total of 126 (25.5%) participants continued to stay in the shelters and received methadone for 6 months, with 125 (25.3%) participants leaving the shelter with continued follow-up at a COSUP site. CONCLUSION: This study demonstrates variability in methadone dosing regimens among shelter residents. As the lockdown measures eased, many chose to leave the shelters, while others remained to receive methadone and other services. The COSUP appears to be effective during periods of increased vulnerability, since a large number of participants were successfully followed up.Contribution: Opioid dependence is a persistent, lifelong disease. It is multifaceted with complex environmental and individual determinants. This study highlighted the use of opioid substitution therapy during a period of increased vulnerability.

A Testimony of Christian Drug Rehabilitation: Transformed by the Power of God.

ABSTRACT: Drug addiction is at crisis level in the United States. Nurses caring for persons affected by substance use disorder (SUD) have a resource in Mr. Ming Ho Liu's testimony on Good TV (Taiwan)-translated and summarized in this article-of his addiction experiences and successful treatment at Operation Dawn, a Christian drug rehabilitation center. Recovery from SUD is possible by God's power. In Mr. Liu's case, his recovery was accomplished without medication.

The Journey From Drug Addiction to Drug Withdrawal: A Christian Gospel Rehabilitation Program in Taiwan.

BACKGROUND: World Drug Report estimates the number of opioid users at 53 million and identifies opioids as responsible for two thirds of the 585,000 people who died as a result of drug use in 2017. PURPOSE: The purpose of this study was to analyze the testimonies of 30 people regarding their journeys from drug addiction to drug withdrawal in Taiwan. METHODS: This was a qualitative research design. The sample inclusion criteria were as follows: (a) being a drug abuser, (b) completed the Christian Gospel Drug Withdrawal Program or church-sponsored program, and (c) shared their related testimony on the Good TV television channel in Taiwan. The participants' stories were posted in Chinese, transcribed by the author, and translated from Chinese into English. Content analysis was used to identify the major themes. RESULTS: Of the 30 participants, 24 were male (80%) and six were female (20%). The major themes identified in their testimonies were: (a) Using illegal drugs related to peer recognition, lack of knowledge, and temptations; (b) drug addiction was an endless pain cycle; (c) turning points related to love, repentance, and hope; (d) drug withdrawal was related to avoiding temptation and overcoming the drug withdrawal syndrome through the Holy Spirit; and (e) outcomes were faith and new life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: In this study, people who received the gospel drug withdrawal programs expressed that their lives had changed, they had withdrawn from drugs successfully, they had become volunteers to help others, and interactions with their family had improved. These programs may be applied in the mental health nursing profession.

Managing acute opioid withdrawal with tramadol during COVID-19 lockdown in a peri-urban setting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response. AIM: To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal. SETTING: Three community-based COSUP sites in Mamelodi (Tshwane, South Africa). METHODS: A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data. RESULTS: Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol. CONCLUSION: Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.

The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study.

BACKGROUND: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. METHODS: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. FINDINGS: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). INTERPRETATION: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. FUNDING: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800).

Pharmacological Management of Heroin Withdrawal Syndrome: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century? STUDY DESIGN: To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Opioid replacement taper with morphine (1927-1947), codeine (1931-1943), and methadone (1951-present) administered for 3-10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000. CONCLUSIONS: The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.

Severe Benzodiazepine Use Disorder in a 16-Year-Old Adolescent: A Rapid and Safe Inpatient Taper.

We describe the case of a 16-year-old boy with a 1-year history of severe benzodiazepine misuse. After being denied access to several treatment programs and hospital centers that felt unprepared to manage benzodiazepine use disorder and withdrawal in an adolescent, the patient was admitted to a tertiary pediatric unit for rapid inpatient tapering and detoxification. The patient was hospitalized for 13 days and received decreasing doses of diazepam under close monitoring of withdrawal symptoms. The taper was well tolerated, and the patient was transferred to a youth residential substance use treatment center, where he completed a successful 2-month placement. This case highlights the lack of adolescent-friendly facilities allowing safe tapering of rapid-acting benzodiazepines in North America. Given high rates of benzodiazepine misuse among youth and the risks associated with benzodiazepine misuse and withdrawal, there is a critical need for more research, provider training, and dedicated resources in this area.

Social housing promotes recovery of wheel running depressed by inflammatory pain and morphine withdrawal in male rats.

The increased use of opioids to treat pain has led to a dramatic increase in opioid abuse. Our previous data indicate that pain may facilitate the development of opioid abuse by increasing the magnitude and duration of opioid withdrawal. The present study tested the hypothesis that social housing would facilitate recovery of activity depressed by pain and opioid withdrawal. Male Sprague Dawley rats were housed either in pairs or alone and then moved to a cage with a running wheel for 6 h daily to assess pain- and opioid withdrawal-induced depression of wheel running. Rats were implanted with two morphine (75 mg each) or placebo pellets to induce opioid dependence and were simultaneously injected with Complete Freund's Adjuvant or saline into the right hind paw to induce persistent inflammatory pain. Hind paw inflammation depressed wheel running whether rats were implanted with a morphine or placebo pellet. Pair-housed rats showed greater recovery of wheel running than individually housed rats. Spontaneous morphine withdrawal precipitated by removal of the morphine pellets caused a reduction in wheel running that was greater in rats with hind paw inflammation compared to pain free rats. Social housing facilitated recovery from withdrawal in rats with hind paw inflammation, but slowed recovery in pain free rats. These data suggest that social housing facilitates recovery by reducing pain both before and during opioid withdrawal. Our findings are consistent with previous studies showing that social buffering reduces pain-evoked responses.

Make Mission Impossible Feasible: The Experience of a Multidisciplinary Team Providing Treatment for Alcohol Use Disorder to Homeless Individuals.

AIM: People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. METHODS: Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). RESULTS: Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042]. CONCLUSION: Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.

Management of opioid use disorder in the USA: present status and future directions.

Opioid use disorder is characterised by the persistent use of opioids despite the adverse consequences of its use. The disorder is associated with a range of mental and general medical comorbid disorders, and with increased mortality. Although genetics are important in opioid use disorder, younger age, male sex, and lower educational attainment level and income, increase the risk of opioid use disorder, as do certain psychiatric disorders (eg, other substance use disorders and mood disorders). The medications for opioid use disorder, which include methadone, buprenorphine, and extended-release naltrexone, significantly improve opioid use disorder outcomes. However, the effectiveness of medications for opioid use disorder is limited by problems at all levels of the care cascade, including diagnosis, entry into treatment, and retention in treatment. There is an urgent need for expanding the use of medications for opioid use disorder, including training of health-care professionals in the treatment and prevention of opioid use disorder, and for development of alternative medications and new models of care to expand capabilities for personalised interventions.

Effectiveness of inpatient withdrawal and residential rehabilitation interventions for alcohol use disorder: A national observational, cohort study in England.

BACKGROUND: This was a national English observational cohort study to estimate the effectiveness of inpatient withdrawal (IW) and residential rehabilitation (RR) interventions for alcohol use disorder (AUD) using administrative data. METHODS: All adults commencing IW and/or RR intervention for AUD between April 1, 2014 and March 31, 2015 reported to the National Drug Treatment Monitoring System (n=3812). The primary outcome was successful completion of treatment within 12months of commencement, with no re-presentation (SCNR) in the subsequent six months, analysed by multi-level, mixed effects, multivariable logistic regression. RESULTS: The majority (70%, n=2682) received IW in their index treatment journey; one-quarter (24%, n=915) received RR; 6% (n=215) received both. Of treatment leavers, 59% achieved the SCNR outcome (IW: 57%; RR: 64%; IW/RR: 57%). Positive outcome for IW was associated with older age, being employed, and receiving community-based treatment prior to and subsequent to IW. Patients with housing problems were less likely to achieving the outcome. Positive outcome for RR was associated with paid employment, self/family/peer referral, longer duration of RR treatment, and community-based treatment following discharge. Community-based treatment prior to entering RR, and receiving IW during the same treatment journey as RR, were associated with lower likelihood of SCNR. CONCLUSIONS: In this first national effectiveness study of AUD in the English public treatment system for alcohol-use disorders, 59% of patients successfully completed treatment within 12months and did not represent for more treatment within six months. Longer duration of treatment and provision of structured continuing care is associated with better treatment outcomes.

Low dose intramuscular methadone for acute mild to moderate opioid withdrawal syndrome.

STUDY OBJECTIVE: To assess the efficacy of 10mg intramuscular (IM) methadone in patients with opioid withdrawal syndrome (OWS). METHODS: This was a prospective observational, convenience sample of patients presenting to the ED with mild to moderate OWS. Evaluations included the Clinical Opiate Withdrawal Scale (COWS), Withdrawal Symptoms Scale (WSS), Altered Mental Status Scale (AMSS) and a physician assessment of the patient's WSS (MDWSS). After enrollment, 10mg of IM methadone was administered and patients were reassessed at 30min post-methadone administration. The primary outcome was the change in COWS at baseline and after methadone administration. Secondary outcomes were the differences between AMSS, and WSS post-methadone. RESULTS: Fifty-seven patients had COWS scores recorded at baseline and 30min. Fifty-six had mild to moderate OWS. The COWS improved a mean of 7.6 after methadone administration (P<0.001). The improvement was greater among patients presenting with moderate versus mild withdrawal (mean decrease=-9.1 vs. -5.5, P<0.001). Patients were more likely to self-score themselves as having withdrawal compared to MDs (93.6% vs. 76.6% respectively, P=0.027). Of the 62 patients with baseline and follow-up WSS by self-assessments, 69% improved post-methadone administration. In addition, the AMSS score remained the same or improved among 86% of cases with measurements at baseline and follow-up. CONCLUSION: A single IM dose of 10mg methadone in the ED reduces the severity of acute mild to moderate OWS by 30min. Larger prospective, randomized controlled, and blinded studies would be needed to confirm these results.

A Longitudinal Qualitative Analysis of the Lived Experience of the Recovery Process in Opioid-Dependent Patients Post-Detoxification.

The aim of the study was to gain an in-depth understanding of opioid-dependent patients' lived experiences post-detoxification. METHOD: The study employed a naturalistic, observational longitudinal design, involving baseline screening and tracking of patients post-detoxification, with follow-up interviews at three, six, and nine months to observe specific processes of interest. This in-depth investigation of patients at four points was new within an Irish context and novel throughout the literature. FINDINGS: Recovery was seen as a process that was not always linear, and lapse and relapse were viewed as part of this process. Patients had great insight into "risk factors for relapse," information and knowledge gained over several years and many treatment episodes. Furthermore, the findings illustrate the role insight plays in any learning and growth experience and the emphasis that is placed upon it within the treatment journey; insight is a fundamental underpinning to any real growth and development. The current article argues that insight merits a more explicit role in the model of recovery capital.

An Evaluation of Practitioner's Experience of Service Users Seeking Community Detoxification from Benzodiazepines.

A recent report in Ireland identified that two-thirds of poisoning deaths involved poly drug use with an average of four different drugs involved. Of these, benzodiazepines were the most common drug group involved. Concern has been expressed regarding high levels of benzodiazepine prescriptions globally. Community-based detoxification programs are required, but detoxification is complex with associated high risks, such as overdose. This study utilized a survey to gather the experiences of a range of drug workers in addiction settings in the southern region of Ireland who are tasked with the management of supporting service users who wish to detoxify from benzodiazepines. The purpose of this study is to identify the issues highlighted in the data and consequently inform policy development, service delivery, future training, and pathways to support service users (SUs). Findings indicate that, while practitioners had high levels of confidence in managing community-based detoxes, levels of knowledge of schedules, contraindications, access to support, and appropriate referral pathways were limited. Barriers to supporting detoxes emerged, emphasizing the importance of multidisciplinary and interagency care planning. Changing trends in drug use led participants to indicate a need for pharmacology training and development of specific local protocols.

Reduction in N2 amplitude in response to deviant drug-related stimuli during a two-choice oddball task in long-term heroin abstainers.

RATIONALE: Chronic heroin use can cause deficits in response inhibition, leading to a loss of control over drug use, particularly in the context of drug-related cues. Unfortunately, heightened incentive salience and motivational bias in response to drug-related cues may exist following abstinence from heroin use. OBJECTIVES: The present study aimed to examine the effect of drug-related cues on response inhibition in long-term heroin abstainers. METHODS: Sixteen long-term (8-24 months) male heroin abstainers and 16 male healthy controls completed a modified two-choice oddball paradigm, in which a neutral "chair" picture served as frequent standard stimuli; the neutral and drug-related pictures served as infrequent deviant stimuli of different conditions respectively. Event-related potentials were compared across groups and conditions. RESULTS: Our results showed that heroin abstainers exhibited smaller N2d amplitude (deviant minus standard) in the drug cue condition compared to the neutral condition, due to smaller drug-cue deviant-N2 amplitude compared to neutral deviant-N2. Moreover, heroin abstainers had smaller N2d amplitude compared with the healthy controls in the drug cue condition, due to the heroin abstainers having reduced deviant-N2 amplitude compared to standard-N2 in the drug cue condition, which reversed in the healthy controls. CONCLUSIONS: Our findings suggested that heroin addicts still show response inhibition deficits specifically for drug-related cues after longer-term abstinence. The inhibition-related N2 modulation for drug-related could be used as a novel electrophysiological index with clinical implications for assessing the risk of relapse and treatment outcome for heroin users.

Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition And Treatment.

Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms.

Alpha2-adrenergic agonists for the management of opioid withdrawal.

BACKGROUND: Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to November week 2, 2015), EMBASE (January 1985 to November week 2, 2015), PsycINFO (1806 to November week 2, 2015), Web of Science, and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine, guanfacine, tizanidine) 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. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered.We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants).Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality).There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. AUTHORS' CONCLUSIONS: Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.