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CORK Bibliography: Detoxification (Opiates)

65 citations. January 2005 to present

Prepared: December 2009

Akerele E; Bisaga A; Sullivan MA; Garawi F; Comer SD; Thomas AA et al. Dextromethorphan and quinidine combination for heroin detoxification. American Journal on Addictions 17(3): 176-180, 2008. (24 refs.)

Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in preclinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms,but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression.

Amato L; Davoli M; Minozzi S; Ali R; Ferri M. Methadone at tapered doses for the management of opioid withdrawal. (review). Cochrane Database of Systemic Reviews (3): CD003409.pub3, 2005. (71 refs.)

Background: Despite widespread use, the evidence of tapered methadone's efficacy in managing opioid withdrawal has not been systematically evaluated. Objectives: To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate. Main results: Sixteen trials involving 1187 people were included. Comparing methadone versus any other pharmacological treatment we observed no clinical difference between the two treatments in terms of completion of treatment. The results of the studies did not show significant differences between the considered treatments. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. Authors' conclusions: Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. 2005, Wiley-Liss.

Amato L; Minozzi S; Davoli M; Vecchi S; Ferri MMF; Mayet S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. (review). Cochrane Database of Systematic Reviews 3(article AR CD005031), 2008. (71 refs.)

Background: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome. Objectives: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status. Search strategy: We searched the Cochrane Drugs and Alcohol Group trials register (27 February 2008). Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), PUBMED (1996 to February 2008); EMBASE (January 1980 to February 2008); CINAHL (January 2003-February 2008); PsycINFO (1985 to April 2003) and reference list of articles. Selection criteria: Randomised controlled trials which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded. Data collection and analysis Three reviewers independently assessed trials quality and extracted data. Main results: Nine studies involving people were included. These studies considered five different psychosocial interventions and two substitution detoxification treatments: Methadone and Buprenorphine. The results show promising benefit from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment relative risk (RR) 1.68 (95% confidence interval (CI) 1.11 to 2.55), use of opiate RR 0.82 (95% CI 0.71 to 0.93), results at follow-up RR 2.43 (95% CI 1.61 to 3.66), and compliance RR 0.48 (95% CI 0.38 to 0.59). Authors' conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this type of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective. Limitations to this review are imposed by the heterogeneity of the assessment of outcomes. Because of lack of detailed information no meta analysis could be performed to analyse the results related to several outcomes.

Arnold-Reed DE; O'Neil P; Holman CDJ; Bulsara MK; Rodiguez C; Gawthorne G et al. A comparison of mental health hospital admissions in a cohort of heroin users prior to and after rapid opiate detoxification and oral naltrexone maintenance. American Journal of Drug and Alcohol Abuse 33(5): 655-664, 2007. (20 refs.)

Mental health (MH) hospital admissions were investigated in a cohort (N 1184) of heroin dependent persons using linked health records. All MH in-patient admissions were extracted 36 months before to 36 months after commencing rapid opioid detoxification (ROD) and oral naltrexone. Results show that the incidence rate ratio (IRR) of drug-related and other MH admissions peaked in the 3 months immediately prior to treatment. All categories subsequently declined to baseline levels by 36 months following treatment. The authors conclude that treatment for heroin dependence reduces risk of MH admissions.

Batki SL; Kauffman JF; Marion I; Parrino MW; Woody GE. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) 43. Rockville MD: Center for Substance Abuse Treatment, 2005. (648 report refs.)

This TIP incorporates the many changes in medication-assisted treatment for opioid addiction that have developed over the past decade. It describes the nature and dimension of opioid use disorders and their treatment, and the historical and regulatory developments. It incorporates recommendations by a consensus panel and evidence-based practices. It also examines the related medical, psychiatric, sociological and substance use disorders and their treatment as part of a comprehensive treatment program. Medications included in the discussion are methadone, LAAM, naltrexone, and buprenorphine. Beyond discussion of the pharmacology of these medications, separate chapters consider screening and assessment, patient-treatment matching, phases of treatment, providing comprehensive care and maximizing client retention, the role of drug testing, associated medical problems, treatment of multiple substance use, treatment of co-occurring disorders, treatment during pregnancy, and administrative issues.

Berglund M; Thelander S; Johnsson E. Treating Alcohol and Drug Abuse: An Evidence Based Review. New York: Jossey-Bass, 2005. (Chapter refs.)

This book provides a review of evidence-based treatments for alcohol and drug problems. It suumarrizes the major treatment approaches and then presents the the findings for over 1,600 studies on treatment outcome and treatment effectiveness. In addition to dealing alchol abuse/dependence interventions for harmful use anre also included. The work is organized into 10 chapters followed by four appendices. The initial chapter provides an overview of approaches to the range of alcohol problems, including hazardous use. The next three chapters consider the psychsocial treatment of alcohol dependence; pharmacotherapy for alcohol withdrawal; pharmacotherapy for alcohol dependence. Chapter 5 considers the longer-term treatment outcomes in alcohol and drug dependence along with the natural history in the absence of treatment. Chapters 6-9 focus upon drug dependence: drug therapy for opiate withdrawal; drug therapy for opiate dependence; and drug therapy for cocaine dependence. The final chapter turns to the impact of substance abuse during pregnancy and the neonatal period.

Blondell RD; Frydrych LM; Arber BC; Bashaw HL; Vexler A; Purdy CH; Sawyer RM; Okazaki S. Randomized trial of extended buprenorphine detoxification for opioid dependency. Journal of Addiction Medicine 2(3): 139-146, 2008. (20 refs.)

Objective: The objective of this study was to determine whether additional "take-home" medication after impatient opioid detoxification would lead to improved rates of subsequent treatment initiation and abstinence. Methods: We randomly assigned 60 inpatients to a 7-day or 37-day extension of sublingual buprenorphine/naloxone after hospitalization. Follow-up telephone interviews were conducted approximately 5 weeks after discharge. The primary outcomes were abstinence, initiation of aftercare outpatient counseling, and initiation of self-help meeting attendance. Results: Of the 30 participants in each group, outcome data were obtained for 25 (83%) in the 7-day extension group and 27 (90%) in the 37-day extension group. There was not a significant difference in the rates of abstinence (53% versus 41%) or initiation of self-help (57% versus 54%) between the 7-day and 37-day groups, respectively. Of those in the 7-day group, 15 (65%) initiated outpatient treatment compared with 21 (88%) of those assigned to the 37-day group. Although not significant in unadjusted analysis (P = 0.093), this difference was significant in regression analysis when controlling for a history of intravenous drug use (P = 0.034). Among all participants, individual characteristics at the time of hospital adimission (eg, age of first drug use, previous history of intravenous drug, type of health insurance) were predictive of outcomes. Conclusions: In this preliminary study, additional medication beyond a week after inpatient detoxification was not associated with clinically important improvements in rates of abstinence or treatment initiation. Baseline patient characteristics seem to affect these clinical outcomes after hospitalization.

Brigham GS; Amass L; Winhusen T; Harrer JM; Pelt A. Using buprenorphine short-term taper to facilitate early treatment engagement. Journal of Substance Abuse Treatment 32(4): 349-356, 2007. (43 refs.)

The U.S. Federal Food and Drug Administration approved buprenorphine for drug abuse treatment in 2002, and it became available for clinical use in early 2003. Maryhaven, a community treatment program, participated in a National Institute on Drug Abuse Clinical Trials Network trial evaluating buprenorphine-naloxone (BNX; Suboxone) short-term taper for medically managed opioid withdrawal and later adopted this treatment. In a retrospective review, the first 64 patients treated with a BNX taper were compared with two groups of patients treated with clonidine before and after the implementation of the BNX program. Significantly more patients (about 80%) receiving BNX continued in further treatment compared to about 30% of those receiving clonidine. Patient outcomes are discussed in the context of the critical need for treatment continuation following detoxification. Common questions of potential adopters of the BNX taper are presented and addressed. Overall, BNX was readily integrated into the existing treatment service.

Buydens-Branchey L; Branchey M; Reel-Brander C. Efficacy of buspirone in the treatment of opioid withdrawal. Journal of Clinical Psychopharmacology 25(3): 230-236, 2005. (31 refs.)

In an attempt to develop a new opiate detoxification approach, the authors assessed the efficacy of buspirone in the treatment of acute heroin withdrawal. Buspirone, a drug interacting with the serotonergic system, was selected because there is evidence that a decrease in serotonergic neurotransmission may be involved in opiate withdrawal symptoms. Twenty-nine hospitalized heroin addicts were randomized to 4 groups: (1) placebo; (2) methadone; (3) buspirone 30 mg daily; (4) buspirone 45 mg daily. The double-blind trial started in all patients with a 5-day methadone stabilization period ending with a 30-mg dose. This was followed from days 6 through 12 by placebo in group 1 and by a methadone taper in group 2. Because of its delayed action, buspirone was started on day 1 in groups 3 and 4 and was continued, after methadone discontinuation, through day 12. On day 13, drugs and placebo were discontinued and patients were observed through day 14. Withdrawal symptoms were assessed with the "Subjective Opiate Withdrawal Scale" (SOWS) and the "Objective Opiate Withdrawal Scale" (OOWS). The SOWS and OOWS scores were significantly higher in the placebo group than in the methadone, buspirone 30 mg, and buspirone 45 mg groups. There were no significant differences in SOWS or OOWS scores when the methadone group was compared with each of the two buspirone groups or when the two buspirone groups were compared with one another. In conclusion, buspirone, a nonopiate drug with no abuse potential, a safe side effect profile and no withdrawal symptoms, at doses of 30 and 45 mg, was as effective as a methadone taper in alleviating the withdrawal symptoms of heroin addicts stabilized for 5 days with, and then withdrawn from, methadone. The use of buspirone could be particularly helpful in outpatient settings where the duration of the methadone taper recommended for detoxification can be lengthy.

Cohen LJ; Gertmenian-King E; Kunik L; Weaver C; London ED; Galynker I. Personality measures in former heroin users receiving methadone or in protracted abstinence from opiates. Acta Psychiatrica Scandinavica 112(2): 149-158, 2005. (46 refs.)

Methadone Maintenance Therapy (MMT) and detoxification to abstinence are among the most common treatment options for opiate-dependent patients. This paper compares personality traits in detoxified former heroin users and those on MMT in order to assess their relevance to treatment selection. Twenty-six formerly heroin-dependent subjects receiving MMT (MM), 33 formerly heroin-dependent subjects withdrawn from MMT (MW), and 43 healthy controls were compared on the Millon Clinical Multiaxial Inventory-II (MCMI-II) and the Temperament and Character Inventory (TCI). On the TCI, MM patients had higher novelty seeking and lower self-directedness scores than controls. Both MM and MW subjects scored higher than controls on multiple MCMI-II scales. MW but not MM subjects scored higher than controls on two Cluster A Scales and the delusional disorder scale. Schizophrenia-spectrum pathology in former opiate users may be greater than previously recognized and could potentially be relevant to treatment selection.

Collins ED; Kleber HD; Whittington RA; Heitler NE. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: A randomized trial. Journal of the American Medical Association 294(8): 903-913, 2005. (71 refs.)

Context: Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence. Objective To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods. Design, Setting, and Patients: A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or 11, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol. Interventions Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction. Main Outcome Measures: Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens. Results Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21 % clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events. Conclusion: These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.

Day E; Eggen J; Ison J; Copello A; Fazil Q. Ethnicity and attempts at self-detoxification from opioid drugs. Drugs: Education, Prevention and Policy 13(1): 93-103, 2006. (15 refs.)

Aims: To compare the motivation for and process of attempting self-detoxification from opioid drugs between White and Asian groups attending a drug-treatment service. Method: Eighty-nine clients (41 Asians, 48 Whites) attending a community opioid detoxification service took part in the study. Data were collected about the number of previous self-detoxification attempts, reasons for self-detoxifying as opposed to accessing a treatment service, psychological and physical strategies employed, and factors leading to relapse. Results: Asian and White clients differed in reasons for attempting a self-detoxification. More Asian clients reported concern about physical and mental health and 'pleasing family', whereas 'criminal justice reasons' were more prevalent in the White group. Both groups reported avoidance and distraction as helpful strategies, but Asian clients were more likely to move away from their home than their White counterparts. White clients reported the use of other drugs as a reason for relapse more often than Asian clients. Conclusions: Results suggest that Asian populations use different strategies for self-detoxification than the White population. This should be taken into consideration when planning treatment services.

Day E; Ison J; Strang J. Inpatient versus other settings for detoxification for opioid dependence. (review). Cochrane Database of Systematic Reviews 2: CD004580.pub2, 2005. (39 refs.)

Background: There are a complex range of variables that can influence the course and subjective severity of opioid withdrawal. There is a growing evidence for the effectiveness of a range of medically-supported detoxification strategies, but little attention has been paid to the influence of the setting in which the process takes place. Objectives To evaluate the effectiveness of any inpatient opioid detoxification programme when compared with all other time-limited detoxification programmes on the level of completion of detoxification, the intensity and duration of withdrawal symptoms, the nature and incidence of adverse effects, the level of engagement in further treatment post-detoxification, and the rates of relapse post-detoxification. Search strategy Electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library Issue 3, 2004); MEDLINE (January 1966-March 2004); EMBASE (January 1988-March 2004); PsycInfo (January 1967-March 2004); CINAHL (January 1982-March 2004). In addition the Current Contents, Biological Abstracts, Science Citation Index and Social Sciences Index were searched. Selection criteria: Randomised controlled clinical trials comparing inpatient opioid detoxifocation (any drug or psychosocial therapy) with other time limited detoxification programmes (including residential units that are not staffed 24 hours per day, day-care facilities where the patient is not resident for 24 hours per day, and outpatient or ambulatory programmes, and using any drug or psychosocial therapy). Data collection and analysis: All abstracts were independently inspected by two reviewers (ED & JI) and relevant papers were retrieved and assessed for methodological quality using Cochrane Reviewers' Handbook criteria. Main results Only one study met the inclusion criteria. This did not explicitly report the number of participants in each group that success fully completed the detoxification process, but the published data allowed us to deduce that 7 out of 10 (70%) in the inpatient detoxification group were opioid-free on discharge, compared with 11 out of 30 (37%) in the outpatient group. There was very limited data about the other outcomes of interest. Authors' conclusions: This review demonstrates that there is no good available research to guide the clinician about the outcomes or cost-effectiveness of in patient or out patient approaches to opioid detoxification.

De Jong CAJ; Laheij RJF; Krabbe PFM. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial. Addiction 100(2): 206-215, 2005. (33 refs.)

Aim: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without anaesthesia. Design: Randomized controlled open clinical trial from September 1999 to August 2001. Setting Four addiction centres in collaboration with three general hospitals in the Netherlands. Participants A total of 272 opioid-dependcnt patients whose previous attempts to abstain were unsuccessful. Intervention Patients received rapid detoxification with general anaesthesia (RD-GA) or without general anaesthesia (RD). Measurements Urine screens and an interview (EuropASI) to assess opioid abstinence; two questionnaires (SOOS, OOWS) to measure withdrawal symptoms and one to measure craving (VAS). Findings: One month after the intervention 62.8% of the patients in the RDGA group and 60.09% in the RD group were abstinent for opioids (P = 0.71). No adverse events or complications occurred during RD: however, in the RD-GA group, five adverse events necessitated admission to a general hospital. The average 1-month cost for RD was EURO2517 versus EURO4439 for RD-GA. Conclusions: Rapid detoxification under general anaesthesia did not result in higher levels of opioid abstinence than rapid detoxification without anaesthesia. The cost of the former intervention was much higher.

Digiusto E; Lintzeris N; Breen C; Kimber J; Mattick RP; Bell J; NEPOD Research Group. Short-term outcomes of five heroin detoxification methods in the Australian NEPOD Project. Addictive Behaviors 30(3): 443-456, 2005. (23 refs.)

This study included 380 participants in five heroin detoxification trials whose data were pooled to enable direct comparison of five detoxification methods in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Rapid detoxification achieved similar initial abstinence rates with either anaesthesia or sedation (average 59%), which were higher than was achieved by inpatient detoxification using clonidine plus other symptomatic medications (24%), which in turn was higher than outpatient detoxification using either buprenorphine (12%) or clonidine plus other symptomatic medications (4%). Older participants and those using more illicit drugs were more likely to achieve abstinence. Entry rates into ongoing post detoxification treatment were as follows: buprenorphine outpatient (65%), sedation (63%), anaesthesia (42%), symptomatic outpatient (27%), and symptomatic inpatient (12%). Post detoxification treatment with buprenorphine or methadone was preferred over naltrexone. Participants with more previous detoxification attempts were more likely to enter post detoxification treatment. Given that outpatient detoxification was more effective with buprenorphine than with symptomatic medications and that rapid detoxification was more effective than the symptomatic inpatient method, the roles of the symptomatic methods should be reconsidered.

Elsner H. Outpatient short-term detoxification treatment of heroin-consumption: 5 days buprenorphine in descending dosage. Suchttherapie 8(3): 119-122, 2007. (1 refs.)

The heroin-consumption only for a short time is a treatment-strategic problem, when the users could not stop the consumption with a 'cold turkey': Mostly a withdrawal-treatment in hospital is not indicated as well as a fairly long-term substitution-treatment. An outpatient withdrawal treatment with methadone often takes several weeks and can impair seriously the general condition and the everyday life function. The following pattern describes an outpatient withdrawal-treatment ("Bochumer Schema") which was found empirically to have an answer for this problem. It uses buprenorphine in descending dosage for 5 days: 8 mg, 6 mg, 4 mg, 2 mg, 1,2 mg. The somatic withdrawal symptoms are suppressed well, but the lack of the psychotropic effects limits the method.

Fiscella K; Moore A; Engerman J; Meldrum S. Management of opiate detoxification in jails. Journal of Addictive Diseases 24(1): 61-71, 2005. (27 refs.)

Little is known about how jails manage opiate withdrawal among arrestees and inmates. We conducted a national Survey of 500 jails in the United States. We specifically asked about assessment and management opiate dependency among arrestees and use of standardized protocols. Among the 245 jails that responded, more than half (56 %) reported they routinely assessed arrestees for opiate dependency and most (59 %) reported using standardized detoxification protocols. Fifty percent of jails used clonidine for detoxification. Very few jails (1%) used methadone or other opiates (2 %) for detoxification. Half of all jails (49 %) failed to use clonidine, methadone or other opiates for detoxification. These results show that many jails fail to use recommended opiate detoxification procedures and highlight the need for uniform national standards for jail management of opiate dependence.

Gossop M. Medically supervised withdrawal as stand-alone treatment. IN: Strain EC; Stitzer ML, eds. The Treatment of Opioid Dependence. Baltimore: Johns Hopkins University Press, 2006. pp. 346-362. (63 refs.)

For treatment aimed at abstinence, a preliminary or first step involves withdrawal/detoxification. (Some treatment programs require people to be drug free at the point of entry.) The natural history of withdrawal is outlined, typically beginning 12 to 15 hours after the last dose of heroin, peaking between 24 to 72 hours, with feelings of discomfort extending for a week to 10 days. Several self-report scales are available, with the individual ranking the severity of the common symptoms -- feeling sick, stomach cramps, muscle tension, aches and pains, runny eyes, insomnia, heart pounding, and yawning. Medications are commonly used to manage withdrawal, most frequently methadone, and dosing schedules are discussed, with the pros and cons of extended approaches to withdrawal are described, i.e. linear versus exponential dosing. The importance of patient education about what is to be anticipated is stressed. Different treatment settings, with their relative limitations and benefits are discussed. Problems associated with treatment dropout are addressed, particularly the risk of overdose upon drug resumption, and the special problems related to withdrawal for those with multiple drug dependencies.

Gowing L; Ali R; White J. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database of Systemic Reviews 2: article CD002022, 2006. (87 refs.)

Background: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. Objectives: To assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in terms of withdrawal signs and symptoms, completion of treatment and adverse effects. Search strategy: We searched the Drugs and Alcohol Group register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004), Medline (January 1966 to January 2005), Embase (January 1985 to January 2005), PsycINFO (1967 to January 2005), and Cinahl (1982 to December 2004) and reference lists of studies. Selection criteria: Controlled trials comparing antagonist-induced withdrawal under heavy sedation or anaesthesia with another form of treatment, or a different regime of anaesthesia-based antagonist-induced withdrawal. Data collection and analysis One reviewer assessed studies for inclusion and undertook data extraction and assessed quality. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. Main results: Six studies (five randomised controlled trials) involving 834 participants met the inclusion criteria for the review. Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably also other forms of detoxification. Authors' conclusions: Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.

Gruber VA; Delucchi KL; Kielstein A; Batki SL. A randomized trial of 6-month methadone maintenance with standard or minimal counseling versus 21-day methadone detoxification. Drug and Alcohol Dependence 94(1/3): 199-206, 2008. (28 refs.)

Background: Important questions remain regarding the necessary duration and intensity for methadone treatment to be effective. Methods: As part of a clinical trial of tuberculosis chemoprophylaxis [Batki, S.L., Gruber, V.A., Bradley, J.M., Bradley, M., Delucchi, K., 2002. A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Drug Alcohol Depend. 66 283-293. doi:10.1016/SO376-8716(01)00208-3], patients with opioid dependence were recruited from an outpatient 21-day methadone detoxification program and were randomly assigned to one of three treatment conditions: (1) continuation in 21-day methadone detoxification; (2) transfer to 6-month methadone maintenance with only minimal counseling; or (3) transfer to 6-month methadone maintenance with standard twice monthly counseling and as-needed social work and psychiatric services. Both the 6-month maintenance treatments were followed by 1.5 months of detoxification. Urine drug tests and self-report measures were collected at baseline, months 1-6, and month 8.5. Results: Compared to 21-day methadone detoxification, 6-month methadone maintenance with either minimal or standard counseling resulted in fewer opiate positive urine tests and days of self-reported heroin and alcohol use. There was no change in cocaine use or other outcome measures. The increased counseling available in the standard counseling condition did not appear to reduce heroin use further than the minimal counseling condition, in contrast to the effect found for more structured counseling in long-term methadone maintenance (McLellan et al., 1993). Conclusions: Six months of methadone maintenance, even with minimal counseling, reduces heroin and alcohol use more than 21-day methadone detoxification.

Grusser SM; Thalemann CN; Platz W; Golz J; Partecke G. A new approach to preventing relapse in opiate addicts: A psychometric evaluation. Biological Psychology 71(3): 231-235, 2006. (23 refs.)

The present study investigated psychological aspects after different methods of withdrawal treatments in opiate addicts had been conducted. Two pharmacological strategies based on delivering an opioid agonist or antagonist were used for withdrawal in opiate addicts. After detoxification, the antagonist was delivered by a pellet implanted subcutaneously. Four days after the beginning of the treatment several psychological variables such as craving, anxiety, depression, and mood were assessed and compared with data from actively consuming opiate addicts and healthy controls. In addition, 6 and 12 weeks later the relapse rates were assessed. Compared with addicts detoxified and treated with Levomethadone as well as actively heroin consuming addicts, subjects treated with Naltrexone demonstrated significantly higher positive psychological outcome concerning all assessed variables and significantly lower relapse rates. Naltrexone implants prove prevention of relapse during the most vulnerable period after detoxification. Compared with Levomethadone withdrawal, they lead to a significantly better psychological condition in patients.

Herman I; Shamir D; Bar-Hamburger R; Pick CG; Schreiber S. The effect of mianserin add-on, on the intensity of opioid withdrawal symptoms during detoxification program: A randomized, double blind, placebo controlled, prospective study. Addictive Behaviors 30(6): 1154-1167, 2005. (34 refs.)

Background: Based on pre-clinical studies regarding the interaction of various antidepressant drugs with the opioid system, we designed a clinical study to be carried out in the 'in-patient detoxification unit' within a large community centre for treatment of drugs dependent people. We evaluated the effect of mianserin add-on, on the intensity of opioid withdrawal symptoms in opiate dependent subjects undergoing medication-supported physical detoxification and integrated psychosocial and psychotherapeutic intervention for the treatment of dependence. Methods: Mianserin (or placebo) was added to the routine medication protocol, during the 3-week in-patient phase of detoxification in a prospective, randomized, double blind, placebo controlled study. Mianserin (or placebo) was continued after discharge and patients were followed up for 3 months in order to evaluate relapse rates. Opiate withdrawal symptoms were assessed during the first 10 days, while depression and anxiety were assessed throughout the 3 months of study. Results: From day 2 onward, patients in the study group showed significantly lower withdrawal symptoms than the control group patients and reached this peak faster (study group 2.8 days, control group 3.2 days, p<0.001). However, drop out rates were higher in the study group throughout the study period and only 13% of the study group patients, compared to 30% of the control group patients reached the end point. Conclusion: Though adding mianserin to the medication treatment during detoxification of opiate-dependent persons attenuated significantly both the intensity and the duration of withdrawal symptoms, the overall drop out rate was negatively influenced in the study group compared to the control group and fewer patients completed the study. Further study is needed in order to establish the origin of the paradox of higher drop out rates in the presence of attenuated intensity and duration of opiate withdrawal symptoms in the study group, and the clinical implications that should be drown.

Kheirabadi GR; Ranjkesh M; Maracy MR; Salehi M. Effect of add-on gabapentin on opioid withdrawal symptoms in opium-dependent patients. Addiction 103(9): 1495-1499, 2008. (25 refs.)

Aims: Evaluation of the efficacy of gabapentin in patients undergoing out-patient treatment for opiate withdrawal. Design A 3-week double-blind, randomized, placebo-controlled trial of adjunctive gabapentin in methadone-assisted detoxification (MAD). Setting: Specialized Addictive Behaviors Unit, an out-patient unit for the treatment of patients with an addictive disorder serving the city of Isfahan (Iran). Participants: Forty out-patients, 37 males and three females, aged 21-61 years, who met DSM-IV criteria for opiate dependence. Intervention Random assignment of subjects to receive adjunctive treatment with either gabapentin (900 mg/day) or placebo under double-blind conditions. Measurements: Severity of subjective withdrawal symptoms using the Subjective Opiate Withdrawal Scale at six stages. Findings Despite the superiority of gabapentin on controlling some of withdrawal symptoms, no significant differences were reported between two groups. Conclusions: Dosage of 900 mg/day of gabapentin is not significantly superior to placebo in controlling opiate withdrawal symptoms.

Kheirabadi GR; Ranjkesh M; Maracy MR; Salehi M. Effect of add-on gabapentin on opioid withdrawal symptoms in opium-dependent patients. Addiction 103(9): 1495-1499, 2008. (25 refs.)

Aims: Evaluation of the efficacy of gabapentin in patients undergoing out-patient treatment for opiate withdrawal. Design: A 3-week double-blind, randomized, placebo-controlled trial of adjunctive gabapentin in methadone-assisted detoxification (MAD). Setting: Specialized Addictive Behaviors Unit, an out-patient unit for the treatment of patients with an addictive disorder serving the city of Isfahan (Iran). Participants Forty out-patients, 37 males and three females, aged 21-61 years, who met DSM-IV criteria for opiate dependence. Intervention Random assignment of subjects to receive adjunctive treatment with either gabapentin (900 mg/day) or placebo under double-blind conditions. Measurements: Severity of subjective withdrawal symptoms using the Subjective Opiate Withdrawal Scale at six stages. Findings: Despite the superiority of gabapentin on controlling some of withdrawal symptoms, no significant differences were reported between two groups. Conclusions: Dosage of 900 mg/day of gabapentin is not significantly superior to placebo in controlling opiate withdrawal symptoms.

Koch AL; Arfken CL; Schuster CR. Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability. Drug and Alcohol Dependence 83(3): 274-278, 2006. (5 refs.)

This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR = 8.34, 95% CI = 5.53, 12.58) and offering medically supervised withdrawal (OR = 2.76, 95% CI = 1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR = 14.32, 95% CI = 7.85, 26.10; and medically supervised withdrawal services, OR = 4.42, 95% CI = 3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

Kovas AE; McFarland BH; McCarty DJ; Boverman JF; Thayer JA. Buprenorphine for acute heroin detoxification: Diffusion of research into practice. Journal of Substance Abuse Treatment 32(2): 199-206, 2007. (48 refs.)

Buprenorphinc has been approved for heroin detoxification, but little is known about its impact on everyday practice. Concerns about buprenorphine include expense, limited knowledge about its use, patient limits, and social and clinical attitudes regarding opioid treatment for heroin dependence. On the other hand, randomized clinical trials suggest that buprenorphine is superior to clonidine with regard to withdrawal symptom relief In June 2004, a community-based residential medical detoxification center switched from clonidine to buprenorphine treatment for all new and returning heroin clients. This study is a retrospective chart review of subject outcomes with clonidine (n = 100) versus buprenorphine (n = 100). Bivariate analysis suggested few cohort differences in pretreatment demographics and client characteristics. In contrast, buprenorphine was significantly associated with increased length of stay and treatment completion. The positive associations between buprenorphine and both treatment completion and length of stay persisted and were slightly enhanced after regression analysis adjusted for potential confounders. Additionally, clinical staff reported better subject engagement in treatment and psychosocial group sessions. This single-site study is an example of successful integration of an evidence-based treatment into community-based practice.

Kuschel C. Managing drug withdrawal in the newborn infant. Seminars in Fetal & Neonatal Medicine 12(2): 127-133, 2007. (56 refs.)

The management of the infant exposed to drugs in utero poses significant challenges. Symptoms and signs of neonatal abstinence syndrome are non-specific but most commonly associated with withdrawal from maternal opioids. A high index of suspicion is required when presented with an infant who could be manifesting symptoms of neonatal abstinence syndrome. In the absence of a reliable history of maternal drug exposure, analysis of neonatal meconium or urine may be indicated. Approximately 90% of infants exposed to opioids will exhibit signs of neonatal abstinence syndrome, although a smaller proportion will require pharmacological treatment. Although few studies have evaluated the advantages of different therapeutic agents and strategies, opioid withdrawal is best treated initially with opioid medication. Supportive care of the infant should include assessment of the adequacy of feeding, evaluation of social circumstances (particularly child protection issues) and surveillance for transmission of viral infection.

Langenfeld S; Birkenfeld L; Herkenrath P; Muller C; Hellmich M; Theisohn M. Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops. Drug and Alcohol Dependence 77(1): 31-36, 2005. (22 refs.)

Background: Treating opioid-addicted women with methadone in pregnancy increased the number of newborns suffering from neonatal abstinence syndrome (NAS). High-pitch crying, insomnia, tremor, myoclonic jerks, vomiting, diarrhoea and poor weight gain were reported symptoms, which were evaluated using the Finnegan (F)-score. Earlier phenobarbital or paregoric had been used to suppress symptoms. We surveyed the administration of pure mu-agonist morphine (MO) in comparison to the alcoholic opioid mixture in tincture of opium (TO). Thirty-three newborns were included in the survey, after informed consent by their parents. Results: NAS started 3-5 days after delivery and lasted for 27 or 30 days (mean) in the TO and MO groups, respectively In either of the tested parameters, we found no significant differences between the two groups (2P < 0.05). The maximum F-score was similar in both groups. but the dose to suppress NAS was higher in the MO group (0.6-0.5 mg/day; total dose 61.6-42.7 mg of morphine). The duration of the therapy was longer in the MO than in the TO group (37.5-32.4 days). On the other hand the weight gain was better in the MO group than in the TO group (25-19 g/day), but was reduced in both groups compared with healthy newborns. Conclusions: Morphine is suitable to treat NAS in a similar manner as tincture of opium, but avoids unwanted effects of the alcoholic extracts with various alkaloids in the tincture of opium and allows better weight gain of the newborns.

Lanier RK; Umbricht A; Harrison JA; Nuwayser ES; Bigelow GE. Evaluation of a transdermal buprenorphine formulation in opioid detoxification. Addiction 102(10): 1648-1656, 2007. (31 refs.)

Aims: Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome. Design Open-label, first-in-humans trial. Setting A residential research facility. Participants Nine physically dependent opioid-users completed the 10-day opioid detoxification study. Interventions Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation. Measures Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected. Findings Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal. Conclusions The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use.

National Quality Forum. National Quality Consensus Standards for the Treatment of Substance Use Conditions: Evidence-Based Treatment Practices. Washington DC: National Quality Forum, 2007

This report grew out of a consensus conference convened by the National Quality Forum. The Executive Summary notes that over the past 15 years, scientific knowledge has substantially increased in respect to treating substance use conditions and that there is growing recognition of substance abuse/dependence as a chronic medical condition. This report assembles a set of 11 detailed, fully specified, evidence-based practices. For each practice the target outcomes are identified, the procedures involved specified, as well as for whom it is intended, the settings in which it is provided, and the personnel involved in providing the services. The practices outlined are applicable across a range of populations, diverse settings, and providers. They fall into four domains - identification of substance use conditions, initiation and engagement in treatment, therapeutic interventions, and continuing care management . These practices include: (1) screening and case finding; (2) adoption of systematic methods and procedures to accomplish case finding; (3) diagnosis and assessment for those with positive screening; (4) brief interventions by a trained clinician; (5) provision of support and other services to promotion initiation of care; (6) management of withdrawal, a necessary precursor of treatment of the substance abuse condition; (7) psychosocial interventions; (8-10) pharmacotherapy for opiate, alcohol and nicotine dependence as an adjunct to psychosocial service; and (11) continuing care management and monitoring. For each of these elements the practice domain is identified, as well as the target outcome, and specification of what is involved. A series of appendices set forth the Members and Board of Directors (drawn from major medical centers, representatives of all major medical professional societies as well as private foundations, and governmental agencies), the members of the Steering Committee and Technical Advisory Panel, selected references, and a summary of the consensus development process.

O'Brien CP. Opiate detoxification: What are the goals? (editorial). Addiction 100(8): 1035-1035, 2005. (1 refs.)

O'Connor PG. Methods of detoxification and their role in treating patients with opioid dependence. (editorial). Journal of the American Medical Association 294(8): 961-963, 2005. (34 refs.)

Oei J; Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependency. (review). Journal of Paediatrics and Child Health 43(1-2): 9-18, 2007. (126 refs.)

Illicit drug use during pregnancy is common and probably underestimated in the majority of published studies. The infant exposed to opiates or other drugs of dependency during intrauterine development is at risk for post-natal withdrawal as well as to long-term problems that are associated with drug-effects and often, adverse social circumstances. This article examines the early management of the infant and mother for detection and monitoring of drug-exposure, pharmacological intervention for withdrawal and the management of associated, particularly infective and psychosocial, problems. Practical concerns surrounding these issues are discussed and further research on psychosocial intervention to improve long-term outcome are much needed.

Oreskovich MR; Saxon AJ; Ellis MLK; Malte CA; Reoux JP; Knox PC. A double-blind, double-dummy, randomized, prospective pilot study of the partial Mu opiate agonist, buprenorphine, for acute detoxification from heroin. Drug and Alcohol Dependence 77(1): 71-79, 2005. (37 refs.)

The optimum dose of buprenorphine for acute inpatient heroin detoxification has not been determined. This randomized, double-blind. double-dummy, pilot study compares two buprenorphine sublingual tablet dosing schedules to oral clonidine. Heroin users (N = 30) who met DSM-IV criteria for opioid dependence and achieved a Clinical Opiate Withdrawal Scale (COWS) score of 13 (moderate withdrawal).were randomized to receive higher dose buprenorphine (HD, 8-8-8-4-2 mg/day on days 1-5), lower dose buprenorphine (LD. 2-4-84-2 mg/day on days 1-5). or clonidine (C, 0.2-0.3-0.3-0.2-0.1 mg QID on days 1-5). COWS scores were obtained QID. Twenty-four hours after randomization. the percentages of subjects who achieved suppression of withdrawal, as defined by four consecutive COWS scores < 12. were: C = 11%, LD 40%, and HD = 60%. Generalized estimating equation regression models. controlling for baseline COWS and time. indicated that COWS scores over the course of 5 days were lower in both LD and HD compared to C (chi(2)(2) = 13.28. P = 0.001). Similar analyses examining, scores over time on the Adjective Rating Scale for Withdrawal (ARSW) and on a Visual Analog Scale of Opiate Craving (VAS) indicated an overall treatment effect on the VAS accounted for by a significant difference between HD and C, but no overall treatment effect on the ARSW. There were no discontinuations due to treatment-related adverse events. Both HD and LD regimens are safe, and efficacious treatment for opioid detoxification, but HD demonstrated superiority to C on a greater number of measures.

Pinkofsky HB; Hahn AM; Campbell FA; Rueda J; Daley DC; Douaihy AB. Reduction of opioid-withdrawal symptoms with quetiapine. Journal of Clinical Psychiatry 66(10): 1285-1288, 2005. (16 refs.)

Objective: To determine the utility of quetiapine in a population undergoing ambulatory detoxification from opioids. Method: Medications utilized in our outpatient clinic for opioid withdrawal were evaluated for quality-assurance purposes. The treatment regimen generally included clonidine, hydroxyzine, trazodone, diphenoxylate/atropine, and sometimes chlordiazepoxide. Patients were also initially given eight 25-mg tablets of quetiapine and instructed to take 1 or 2 tablets every 4 hours as needed for symptoms of withdrawal or craving (with a maximum daily dose of 200 mg). Data were based on patient evaluations from June 2003 to June 2004. Results: 41% of all patients (N = 213) successfully completed the detoxification phase of the program (i.e., completed at least 5 days of abstinence). A medication questionnaire was instituted for quality-assurance purposes after some apparent initial success with quetiapine. A retrospective analysis of these data revealed that, of the 107 patients evaluated for medication response, 79 reported that quetiapine helped reduce craving for opioids, 52 reported that quetiapine helped reduce their anxiety, 24 reported a reduction in somatic pain, 22 reported that quetiapine helped alleviate insomnia, and 14 reported an improved appetite. Four individuals did not feel quetiapine had any benefit, and another 7 were unable to tolerate quetiapine because of side effects. The quetiapine dose used ranged from 25 to 600 mg/day (mean +/- SD dose = 206 +/- 122 mg/day). Conclusions: Quetiapine use during opioid cessation was found to help abate symptoms of opioid withdrawal in our patient population and was generally well tolerated.

Pollice R; Casacchia M; Bianchini V; Mazza M; Conti CM; Roncone R. Severe tramadol addiction in a 61 year-old woman without a history of substance abuse. International Journal of Immunopathology and Pharmacology 21(2): 475-476, 2008. (9 refs.)

We describe here the first case of Tramadol addiction and withdrawal in an elderly female patient in apparently good physical health. We report successful treatment with mirtazapine and clonidine. We believe that patients must be advised to take Tramadol regularly and to stop gradually especially after long treatment periods; moreover physicians must consider the potential physical dependence when they prescribe Tramadol for pain. Hence, we are observing some patients who continue to take Tramadol in order "to achieve a feeling of well-being," even though their pain is controlled after disease regression. Finally, the establishing of an evidence-based Tramadol detoxification protocol would be highly desirable.

Raistrick D; West D; Finnegan O; Thistlethwaite G; Brearley R; Banbery J. A comparison of buprenorphine and lofexidine for community opiate detoxification: Results from a randomized controlled trial. Addiction 100(12): 1860-1867, 2005. (22 refs.)

Objective: To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen. Design: An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments. Methods Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271). Results: A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results Conclusions: Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome.

Sarkar S; Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: A national survey. Journal of Perinatology 26(1): 15-17, 2006. (13 refs.)

Aims: To determine the monitoring and treatment of neonatal abstinence syndrome (NAS) in neonatal intensive care units (NICUs) following opiate or polydrug exposure in utero. Methods:A pretested questionnaire was distributed via email to the chiefs of the neonatology divisions with accredited Fellowship programs in Neonatal-Perinatal Medicine in the United States.Results:Of the 102 individuals contacted, 75 participated in the survey. In all, 41 of the respondents (54.5%) have a written policy regarding the management of neonatal NAS. The method of Finnegan is the most commonly used abstinence scoring system (49 of 75, 65%), while only three respondents use the Lipsitz tool. Opioids (tincture of opium, or morphine sulfate solution) are used most commonly for management of both opioid (63% of respondents) and polydrug (52% of respondents) withdrawal, followed by phenobarbital (32 % of respondents) for polydrug withdrawal and methadone (20% of respondents) for opioid withdrawal. In all, 53 respondents (70%) use phenobarbital, and 19 (25%) use intravenous morphine to control opioid withdrawal seizures, while 61 (81%) use phenobarbital in cases of polydrug withdrawal seizures. Only 53 respondents (70%) always use an abstinence scoring system to determine when to start, titrate, or terminate pharmacologic treatment of neonatal NAS. Conclusion: The management of neonatal psychomotor behavior consistent with withdrawal varies widely, with inconsistent policies to determine its presence or treatment. Only about half of NICUs have written guidelines for the management of NAS, which may preclude effective auditing of this practice. Educational interventions may be necessary to ensure changes in clinical practice.

Scherbaum N; Kluwig J; Meiering C; Gastpar M. Use of illegally acquired medical opioids by opiate-dependent patients in detoxification treatment. European Addiction Research 11(4): 193-196, 2005. (9 refs.)

Take-home dosages in maintenance treatment are of great therapeutic importance, but they include the risk of the substitute being distributed illegally. We reviewed the extent of consumption of illegally acquired medical opiates by 142 opiate- or poly-addicted patients consecutively admitted to a detoxification ward. 76 (53.5%) of them admitted to taking illegally acquired medical opiates, usually methadone, at least once. The cumulative duration was 30 days (median). Motivation was usually due to difficulties in acquiring heroin, however one third reported use in an attempt at self-detoxification or as transition before entering maintenance treatment. Maintenance patients were usually the source of the opiates. The results prove the necessity of stringent conditions for take-home dosages, and illustrate deficits in the health care system.

Seifert J; Metzner C; Paetzold W; Borsutzky M; Ohlmeier M; Passie T et al. Mood and affect during detoxification of opiate addicts: A comparison of buprenorphine versus methadone. Addiction Biology 10(2): 157-164, 2005. (66 refs.)

Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.

Shanahan MD; Doran CM; Digiusto E; Bell J; Lintzeris N; White J et al. A cost-effectiveness analysis of heroin detoxification methods in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Addictive Behaviors 31(3): 371-387, 2006. (39 refs.)

This economic evaluation was part of the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) project. Data from four trials of heroin detoxification methods, involving 365 participants, were pooled to enable a comprehensive comparison of the cost-effectiveness of five inpatient and outpatient detoxification methods. This study took the perspective of the treatment provider in assessing resource use and costs. Two short-term outcome measures were used-achievement of an initial 7-day period of abstinence, and entry into ongoing post-detoxification treatment. The mean costs of the various detoxification methods ranged widely, from AUD $491 (buprenorphine-based outpatient); to AUD $605 for conventional outpatient; AUD $1404 for conventional inpatient; AUD $1990 for rapid detoxification under sedation; and to AUD $2689 for anaesthesia per episode. An incremental cost-effectiveness analysis was carried out using conventional outpatient detoxification as the base comparator. The buprenorphine-based outpatient detoxification method was found to be the most cost-effective method overall, and rapid opioid detoxification under sedation was the most cost-effective inpatient method.

Shanahan CW; Lincoln A; Horton NJ; Saitz R; Winter M; Samet JH. Relationship of depressive symptoms and mental health functioning to repeat detoxification. Journal of Substance Abuse Treatment 29(2): 117-123, 2005. (55 refs.)

To better understand residential detoxification use, we assessed the roles of depressive symptoms (DS) and mental health functioning (MHF) on repeat detoxification. A prospective cohort of residential detoxification patients (N = 400) without primary medical care was followed over 2 years at 6-month intervals. Subsequent detoxification admissions were examined using a statewide administrative database and DS (Center for Epidemiologic Studies Depression Scale) and MHF (SF-36 mental component summary subscale) measurements at follow-up. Incidence rate ratios of return to detoxification were estimated using multivariable longitudinal Poisson regression. In separate analyses, greater DS and worse MHF predicted higher detoxification use rates. Clinically significant worsening (10 points) of DS and MHF on objective scales predicted a 20% increased rate of detoxification readmission. Male sex, heroin as a problem substance, and race/ethnicity each predicted detoxification use. These data suggest that identifying individuals with DS or worse MHF after detoxification may provide opportunities for clinical intervention to reduce recurrent residential detoxification.

Shi J; Xu GZ; Liu TT; Wang X; Shen LY; Li J et al. A comparative clinical study of the effects of the traditional Chinese medicine jinniu capsules and lofexidine on acute heroin withdrawal symptoms. American Journal of Drug and Alcohol Abuse 34(6): 792-800, 2008. (17 refs.)

Objective: Jinniu capsules, comprised of herbs and marine product extracts, are traditionally used in Chinese medicine. In this randomized multicenter clinical trial we evaluated the efficacy and safety of Jinniu capsules used to treat the symptoms of heroin withdrawal, as compared with lofexidine. Methods: Two hundred and twelve patients with heroin dependence were randomly assigned to the Jinniu capsule or lofexidine treatment groups during a 10-day double-blind clinical trial. The severity of their opiate withdrawal symptoms was measured daily for 10 days. Anxiety was measured on days 0, 5, and 10. Safety assessment of the drugs included measurement of vital signs and side effects, as well as laboratory tests. Results: Withdrawal symptom and anxiety scores decreased gradually over the treatment period, and no significant differences were found between two groups. No severe adverse events occurred during the treatment. Conclusion: Jinniu capsules may be an effective and safe agent in the management of opiate withdrawal.

Soeffing JM; Rastegar DA. Treatment completion on an inpatient detoxification unit: Impact of a change to sublingual buprenorphine-naloxone. Journal of Substance Abuse Treatment 33(4): 401-404, 2007. (16 refs.)

Purpose: Buprenorphine is commonly used for opioid detoxification. The goal of this study was to determine whether a change from the intramuscular (IM) buprenorphine to the sublingual (SL) formulation of buprenorphine-naloxone was associated with improved treatment completion rates on an inpatient detoxification unit. Methods: This study was conducted at the Johns Hopkins Bayview Medical Center (JHBMC) Chemical Dependence Unit (CDU), a 26-bed, 3-day inpatient detoxification unit providing detoxification from opioids, alcohol, and sedatives. The opioid detoxification protocol was changed from IM buprenorphine (0.3 mg bid for 3 days) to SL buprenorphine-naloxone (8, 8, and 6 mg on sequential days, plus 2 mg on the morning of discharge). For the 3 months prior to and after the change in protocol, data were collected retrospectively on demographics, type of dependence being treated, and type of discharge. Findings: A total of 1,168 patients were admitted to the JHBMC CDU during the period studied. In the 3 months prior to the change in buprenorphine protocol, 353 of 483 patients admitted for treatment of opioid dependence (73.1%) completed treatment, compared with 407 of 473 patients admitted after the change (86.0%); this difference was highly significant (p < .0001). Among 212 patients who did not receive treatment for opioid dependence over the same period, the rates of treatment completion did not change significantly (89.8% before vs. 83.0% after; p = .208). Conclusions: A change from IM buprenorphine to SL buprenorphine-naloxone for opioid detoxification was associated with a significant improvement in completion rates at this inpatient treatment program.

Somogyi AA; Larsen M; Abadi RM; Jittiwutikarn J; Ali R; White JM. Flexible dosing of tincture of opium in the management of opioid withdrawal: Pharmacokinetics and pharmacodynamics. British Journal of Clinical Pharmacology 66(5): 640-647, 2008. (24 refs.)

AIMS: The aim was to evaluate the clinical effectiveness, pharmacodynamics and pharmacokinetics of a range of Tincture of Opium (TOP) doses in the management of opioid withdrawal. METHODS: Forty-five opium-dependent Thai subjects were allocated to three dosing groups (6.66, 13.3 and 20 mg morphine equivalents, twice daily) depending on their self-reported prior opium use. On day 5 of dosing subjects underwent an interdosing interval study where blood, withdrawal scores, heart rate and blood pressure (BP) were collected at 0, 1, 3 and 8 h. Plasma morphine concentrations were quantified by high-performance liquid chromatography, and plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations by LCMS. RESULTS: Thirty-two subjects completed the study. Withdrawal scores were low for all subjects (range 9-23% of maximum response). There were dose-dependent changes in both systolic and diastolic BP (P = 0.021 and P = 0.01, respectively), but these were not considered clinically significant. There were no effects of dose on respiratory rate. Plasma morphine concentrations changed significantly across the interdosing interval (P = 0.0001), rising to a maximum at 1 h after dosing. Plasma morphine concentrations also differed according to dose (P < 0.05). The mean ratios of the morphine glucuronides were found to be: M3G/M6G = 7.7, M3G/morphine = 35.6 and M6G/morphine = 4.9, values comparable to those previously reported. CONCLUSION: The management of opioid withdrawal can be achieved, with minimal adverse effects, by using flexible dosing of TOP.

Strain EC; Stitzer ML, eds. The Treatment of Opioid Dependence. Baltimore: Johns Hopkins University Press, 2006. (Chapter refs.)

This book reflects the new developments in treatment protocols for opioid depedence. Beyond methadone additional chapters cover the pharmacology and clinical use of buprenorphine as well as the latest research on Naltrexone, Clonidine, and Lofexidine. The volume also includes chapters on pain and prescription opioids as well as medication-free treatment and medically supervised alternatives to opioid substitute treatments, including withdrawal.

Sullivan MA; Nunes EV. New-onset mania and psychosis following heroin detoxification and naltrexone maintenance. (letter). American Journal on Addictions 14(5): 486-487, 2005. (5 refs.)

Sullivan MA; Rothenberg JL; Vosburg SK; Church SH; Feldman SJ; Epstein EM et al. Predictors of retention in naltrexone maintenance for opioid dependence: Analysis of a stage I trial. American Journal on Addictions 15(2): 150-159, 2006. (59 refs.)

Behavioral naltrexone therapy (BNT) was developed to address the shortcomings of naltrexone maintenance for opiate dependence and improve compliance by integrating several empirically validated methods, including the use of a significant other to monitor compliance, voucher incentives, and motivational techniques. An uncontrolled Stage I pilot trial (N = 47) of BNT was conducted. Baseline demographic and clinical variables were evaluated as predictors of retention with univariate tests. Significant predictors were entered together into a multiple regression model. Poorer ( shorter) retention in treatment was associated with methadone use and higher average bags per day of heroin. Other variables that became non-significant in multiple regression analysis included older age and depressive symptoms. Individuals with greater physiologic dependence and/or dependence on longer-acting opiates are at higher risk to drop out from naltrexone maintenance and may require a more gradual detoxification and more intensive behavioral therapy aimed at enhancing initial compliance.

Teesson M; Havard A; Ross J; Darke S. Outcomes after detoxification for heroin dependence: Findings from the Australian Treatment Outcome Study (ATOS). Drug and Alcohol Review 25(3): 241-247, 2006. (18 refs.)

As part of the Australian Treatment Outcome Study (ATOS), 177 (88%) heroin users entering detoxification (DTX) and 66 (83%) heroin users not in treatment (NT) were interviewed at baseline and 3 months to examine drug use, risk-taking, overdose, crime and psychopathology outcomes. The majority (76%) of the DTX group had entered additional treatment at 3 months, mainly further detoxification, and 54% were currently in treatment, mainly maintenance and residential rehabilitation. There were reductions in heroin use and other drug use in those entering detoxification. Forty-two per cent were abstinent at 3 months compared to 20% in the NT group. There were also reductions in crime among those entering DTX, and less marked reductions in the NT group. Psychopathology showed less change. Detoxification may, in some part, function as a gateway to further treatment and those entering DTX showed modest but significant improvements across drug use and crime at 3 months.

Threlkeld M; Parran TV; Adelman CA; Grey SF; Yu JH. Tramadol versus buprenorphine for the management of acute heroin withdrawal: A retrospective matched cohort controlled study. American Journal on Addictions 15(2): 186-191, 2006. (13 refs.)

Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the m receptor. Despite this m receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine ( 1996-1997) versus tramadol ( 1999-2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence ( ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used ( bags/day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched ( 45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous pilot reports that indicated few clinical differences between parenteral buprenorphine and oral tramadol protocols when used in the management of acute heroin withdrawal. As a consequence, tramadol shows some promise as an opioid withdrawal management medication.

Wallen MC; Lorman WJ; Gosciniak JL. Combined buprenorphine and clonidine for short-term opiate detoxification: Patient perspectives. Journal of Addictive Diseases 25(1): 23-31, 2006. (21 refs.)

The approval in 2003 for the use of buprenorphine in opiate addiction treatment has provided physicians with a new pharmacological tool to combat opiate addiction. We surveyed a sample of 100 inpatients who completed short-term opiate detoxification treatment utilizing, a combination of buprenorphine and clonidine to assess patient perspectives regarding the usefulness and tolerability of this medication regimen and to compare it to their past opiate detox experiences, if any. Patients identified pain (63%), sleep problems (57%), and anxiety (56%) as the symptoms they perceived to be most helped with buprenorphine. Over 90% of patients with past detoxification treatments rated buprenorphine treatment to be as good as or better than their past treatments. Reports of a euphoric effect were minimal (7%) and no patients reported any generalized worsening of their opiate withdrawal symptoms. We conclude that based upon patient perspectives that combining buprenorphine with clonidine is a useful and well-tolerated medication regimen for the treatment of opiate withdrawal.

Yu E; Miotto K; Akerele E; Montgomery A; Elkashef A; Walsh R et al. A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug and Alcohol Dependence 97(1-2): 158-168, 2008. (42 refs.)

Context: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals Undergoing medically supervised opioid detoxification as compared to placebo. Design: An inpatient, Phase 3. placebo-controlled. double-blind. randomized mufti-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (clays 4-8). and (3) post detoxification/medication phase (days 9-11). Subjects: Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main outcome measure: Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). Results: Due to significant findings. the study was terminated early. On the study clay 5 MHOWS. Subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5 +/- 2.1 versus 30.9 +/- 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions: Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.

Zullino DF; Krenz S; Eap CB; Benguettatt D; Khan R. Over- and underreporting of recent drug use in subjects entering an inpatient detoxification unit. European Journal of Medical Research 13(1): 15-20, 2008. (15 refs.)

Underreporting of drug use is commonly found more often than overreporting. Overreporting may; however, occur in particular settings, e.g. in subjects entering a detoxification program. Methods: Self-reports (standardized semi structured interview) of recent drug use of 554 patients consecutively admitted to a drug detoxification inpatient unit were compared to urine screening results at admission. Overreporters were defined as indicating a consumption of a specific drug during the preceding 7 days (3 days for cocaine) which was not confirmed by the urine screening. Underreproters denied consumption but presented positive urine. Results: Overreporting was especially prevalent for opiates, and relatively more frequent (59.9% heroin, 40% methadone) than underreporting (6.8% heroin, 20.4% methadone). Signs of intoxication at admission, current methadone substitution, and previous institutional detoxification experiences influenced opiate overreporting. Conclusions: Some of the retained parameters predicting overreporting of recent opiate consumption corroborated the hypothesis of patients trying to receive more consideration from the therapeutic team and to get more intensive pharmacological care.

Ansari MA; Memon Z; Ahmed SP; Ali M. Comparison of the efficacy and safety of chlorpromazine with verapamil for the treatment of acute opioid abstinence syndrome. Pakistan Journal of Medical Sciences 25(4): 641-645, 2009. (20 refs.)

Objective: To compare the efficacy and safety of chlorpromazine with Verapamil in patients with acute opioid Abstinence Syndrome. Methodology: Single blind comparative clinical trial was conducted at Department of Pharmacology, BMSI, JPMC, Karachi, over the period of one year. Forty opiate-dependent subjects were chosen at random who were in search of opioid abstinence treatment. All patients were grouped into two groups, group-I received chlorpromazine 150 mg/day and group-II received Verapamil 120mg/day in divided doses. Every patient completed the management plan while admitted in the hospital for 10 days. Results: The chlorpromazine showed decreased efficacy and safety, whereas verapamil showed clinically pertinent decline in the subjective symptoms of acute opioid abstinence syndrome. Conclusion: The study showed Verapamil is superior to chlorpromazine in the treatment of opioid abstinence syndrome indicated by better reduction of withdrawal symptom scores, excessive opioid urinary excretion and lees side effects. The superiority of verapamil over chlorpromazine in controlling opioid abstinence syndrome may indicate that calcium is involved in the initiation and development of opioid abstinence syndrome.

Bearn J; Swami A; Stewart D; Atnas C; Giotto L; Gossop M. Auricular acupuncture as an adjunct to opiate detoxification treatment: Effects on withdrawal symptoms. Journal of Substance Abuse Treatment 36(3): 345-349, 2009. (21 refs.)

It was hypothesized that auricular acupuncture would lead to reduced severity of opiate withdrawal symptoms and craving when provided as an adjunct to methadone detoxification. The study used a randomized, placebo-controlled study design. The sample consisted of 83 drug misusers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for opiate dependence. Daily measures of withdrawal severity and craving were taken using the Short Opiate Withdrawal Scale and an eight-item craving questionnaire. Urine screening was used as an objective assessment of treatment adherence. The study hypothesis was not confirmed. Auricular acupuncture had no effect upon withdrawal severity or craving when provided as an adjunct to a standard methadone detoxification treatment. The results are consistent with the findings of other studies that failed to find any effect of acupuncture in the treatment of drug dependence. The failure to find any clinical gains from the adjunctive use of auricular acupuncture during detoxification from opiates raises concerns about the widespread acceptance of this intervention.

Gowing L; Ali R; White JM. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database of Systematic Reviews 4(CD002021), 2009. (83 refs.)

Back ground: Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of long-term substitution treatment. Objectives: To assess the effectiveness of opioid antagonists in combination with minimal sedation to manage opioid withdrawal. Search strategy: 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. Selection criteria Controlled studies of interventions involving the use of opioid antagonists in combination with minimal sedation to manage withdrawal in opioid-dependent participants compared with other approaches or different opioid antagonist regimes. Data collection and analysis: One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors. Main results: Nine studies (6 randomised controlled trials), involving 837 participants, met the inclusion criteria for the review. The quality of the evidence is low, but suggests that withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, while the overall severity is less. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone). In some situations antagonist-induced withdrawal may be associated with significantly higher rates of completion of treatment, comp[ared to withdrawal managed primarily with adrenergic agonists. However, this outcome has not been produced consistently, and the extent of any benefit is highly uncertain. Authors' conclusions: The use of opioid antagonists combined with alpha(2)-adrenergic agonists is a feasible approach to the management of opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist. A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium. Further research is required to confirm the relative effectiveness of antagonist-induced regimes, as well as variables influencing the severity of withdrawal, adverse effects, the most effective antagonist-based treatment regime, and approaches that might increase retention in subsequent naltrexone maintenance treatment.

Gowing L; Ali R; White JM. Buprenorphine for the management of opioid withdrawal. (review). Cochrane Database of Systemic Reviews 3: article CD002025, 2009. (142 refs.)

Background: Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of substitution treatment. Objectives: To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal and adverse effects. Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966 to July 2008), EMBASE (January 1985 to 2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles. Selection criteria: Randomised controlled trials of interventions involving the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes. Data collection and analysis: One author assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all authors. Main results: Twenty-two studies involving 1736 participants were included. The major comparisons were with methadone (5 studies) and clonidine or lofexidine (12 studies). Five studies compared different rates of buprenorphine dose reduction. Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. It appears that completion of withdrawal treatment may be more likely with buprenorphine relative to methadone (RR 1.18; 95% CI 0.93 to 1.49, P = 0.18) but more studies are required to confirm this. Relative to clonidine or lofexidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer (SMD 0.92, 95% CI 0.57 to 1.27, P<0.001), and are more likely to complete withdrawal treatment (RR 1.64; 95% CI 1.31 to 2.06, P<0.001). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine. Authors' conclusions: Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal.

Jones H. Scientific evidence and practical experience with methadone-assisted withdrawal of heroin-dependent pregnant patients. Heroin Addiction and Related Clinical Problems 10(4): 33-38, 2008

Opioid dependence during pregnancy is a complex multi-faceted medical challenge that, if untreated, places the mother and child at risk for life threatening consequences. While methadone maintenance is the accepted standard of care for opioid dependent patients who are pregnant, there are limited circumstances when this life saving medication may not be an immediate option. Thus, this paper first highlights the data supporting the current USA clinical guidelines regarding medication-assisted withdrawal during pregnancy in opioid-dependent patients. Next, the results of a retrospective study comparing the maternal and neonatal consequences of methadone-assisted withdrawal to methadone maintenance in pregnant opioid-dependent patients are summarized. Given the generally poorer maternal outcomes of the medication-assisted withdrawal patients, these data provide renewed and current support for methadone-maintenance as the first-line treatment approach for opioid-dependent pregnant women.

Katz EC; Schwartz RP; King S; Highfield DA; O'Grady KE; Billings T et al. Brief vs. extended buprenorphine detoxification in a community treatment program: Engagement and short-term outcomes. American Journal of Drug and Alcohol Abuse 35(2): 63-67, 2009. (27 refs.)

Background: Despite evidence supporting the efficacy of buprenorphine relative to established detoxification agents such as clonidine, little research has examined: 1) how best to implement buprenorphine detoxification in outpatient settings; and 2) whether extending the length of buprenorphine detoxification improves treatment engagement and outcomes. Objectives: The current study examined the impact on 1) successful detoxification completion; 2) transition to longer-term treatment; and 3) treatment engagement of two different length opioid detoxifications using buprenorphine. Methods: The study compared data obtained from two consecutive studies of early treatment engagement strategies. In one study (n = 364), opioid-addicted participants entered treatment through a Brief (5-day) buprenorphine detoxification. In the other study (n = 146), participants entered treatment through an Extended (i.e., 30-day) buprenorphine detoxification. Results: Results indicated a greater likelihood of successful completion and of transition among participants who received the Extended as compared to the Brief detoxification. Extended detoxification participants attended more counseling sessions and submitted fewer drug-positive urine specimens during the first 30 days of treatment, inclusive of detoxification, than did Brief detoxification participants. Conclusions: Results demonstrate that longer periods of detoxification improve participant engagement in treatment and early treatment outcomes. Scientific Significance: Current findings demonstrate the feasibility of implementing an extended buprenorphine detoxification within a community-based treatment clinic.

Liu TT; Shi J; Epstein DH; Bao YP; Lu L. A meta-analysis of Chinese herbal medicine in treatment of managed withdrawal from heroin. Cellular and Molecular Neurobiology 29(1): 17-25, 2009. (42 refs.)

Chinese herbal medicine has shown promise for heroin detoxification. This review extends a prior meta-analysis of Chinese herbal medicine for heroin detoxification, with particular attention to the time course of symptoms. Both English and Chinese databases were searched for randomized trials comparing Chinese herbal medicine to either alpha 2-adrenergic agonists or opioid agonists for heroin detoxification. The methodological quality of each study was assessed with Jadad's scale (1-2 = low; 3-5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; outcome measures assessed were withdrawal-symptoms score, anxiety, and adverse effects of treatment. Twenty-one studies (2,949 participants) were included. For withdrawal-symptoms score relieving during the 10-day observation, Chinese herbal medicine was superior to alpha 2-adrenergic agonists in relieving opioid-withdrawal symptoms during 4-10 days (except D8) and no difference was found within the first 3 days. Compared with opioid agonists, Chinese herbal medicine was inferior during the first 3 days, but the difference became non-significant during days 4-9. Chinese herbal medicine has better effect on anxiety relieving at late stage of intervention than alpha 2-adrenergic agonists, and no difference with opioid agonists. The incidence of some adverse effects (fatigue, dizziness) was significantly lower for Chinese herbal medicine than for alpha 2-adrenergic agonists (sufficient data for comparison with opioid agonists were not available). Findings were robust to file-drawer effects. Our meta-analysis suggests that Chinese herbal medicine is an effective and safety treatment for heroin detoxification. And more work is needed to determine the specific effects of specific forms of Chinese herbal medicine.

Mannelli P; Patkar AA; Peindl K; Gorelick DA; Wu LT; Gottheil E. Very low dose naltrexone addition in opioid detoxification: A randomized, controlled trial. Addiction Biology 14(2): 204-213, 2009. (49 refs.)

Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence.

Mannelli P; Patkar AA; Peindl K; Gottheil E; Wu LT; Gorelick DA. Early outcomes following low dose naltrexone enhancement of opioid detoxification. American Journal on Addictions 18(2): 109-116, 2009. (47 refs.)

Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence.

Minozzi S; Amato L; Davoli M. Detoxification treatments for opiate dependent adolescents. (review). Cochrane Database of Systemic Reviews 2009(2): article CD006749, 2009. (33 refs.)

Background: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless no studies have been published which systematically assess the effectiveness of the pharmacological detoxification among adolescents. Objectives: To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status. Search strategy: We searched the Cochrane Central Register of Controlled Trials (August 2008), MEDLINE (January 1966 to August 2008), EMBASE (January 1980 to August 2008), CINHAL (January 1982 to August) and reference lists of articles. Selection criteria: Randomised and controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13-18 years). Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Main results: One trial involving 36 participants was included. It compares buprenorphine with clonidine for detoxification. No difference was found for drop out: RR 0.45 (95% CI: 0.20 - 1.04) and acceptability of treatment: withdrawal score WMD: 3.97 (95% CI -1.38, 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 [ 95% CI 1.58, 76.55]. Authors' conclusions: It is difficult to draft conclusions on the basis of only one trial with few participants. Furthermore, the only study included did not consider the efficacy of methadone that is still the most frequent drug utilized for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people for to practical and ethical reasons.

Orman JS; Keating GM. Spotlight on buprenorphine/naloxone in the treatment of opioid dependence. CNS Drugs 23(10): 899-902, 2009. (25 refs.)

Buprenorphine/naloxone (Suboxone (R)) comprises the partial p-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4: 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination. Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence.

Ridge G; Gossop M; Lintzeris N; Witton J; Strang J. Factors associated with the prescribing of buprenorphine or methadone for treatment of opiate dependence. Journal of Substance Abuse Treatment 37(1): 95-100, 2009. (23 refs.)

The study investigates patient preferences and beliefs and treatment program factors related to the decision to prescribe either buprenorphine or methadone to opiate-dependent patients. The sample (N = 192) was recruited from 10 addiction treatment services in London. Data were collected by means of a single structured interview conducted with patients commencing a treatment episode at the participating agencies. Data on patient demographics, beliefs, attitudes, and preferences were collected using a structured interview. Data regarding treatment goals and prescribed medication were collected from interviews with clinical staff. Oral methadone had a higher preference rating than buprenorphine. Clinical prescribing practices were influenced by patient preferences (both positive and negative), by prior treatment experiences, and by Current treatment goals. Patient preferences and beliefs about opioid agonist medications served as an important influence upon clinical prescribing practices. The odds of being prescribed buprenorphine were three times greater among those patients who reported a preference for buprenorphine. The odds of receiving a prescription for methadone were about twice as great among those for whom methadone was the more preferred medication. Preferences were related to previous treatment experiences with these opioid agonists, and for patients in both groups., personal experience was the most important source of information about the treatment options. Buprenorphine was more likely to be prescribed for short-term detoxification and methadone for maintenance treatment.

Rokhlina M; Kitkina T; Gubanov G. Paxil (Paroxetine) in complex therapy in heroin addicts. Heroin Addiction and Related Clinical Problems 9(1): 45-54, 2007

The efficiency of Paroxetine was studied in 27 males with heroin addiction (average age: 26.2 years, average disease duration: 3.4 years) undergoing detoxification. After 3-4 days of paroxetine (initial dose 20 mg/day, maximum dose 40 mg/day) the first improvement of affective symptoms were noticed. By the 14th day of treatment, affective discomfort had been arrested in most cases. On the whole paroxetine can be considered an effective medicine for contrasting affective discomfort of heroin addicts in the post-withdrawal stage, as long as agonist compounds are not available.

Sheard L; Wright NMJ; El-Sayeh HG; Adams CE; Li R; Tompkins CNE. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification. Substance Abuse Treatment, Prevention and Policy 4: e-article 1, 2009. (32 refs.)

Background: Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine. Methods: Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. Results: 64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02-2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. Conclusion: These findings would suggest that dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting.

Sigmon SC; Dunn KE; Badger GJ; Heil SH; Higgins ST. Brief buprenorphine detoxification for the treatment of prescription opioid dependence: A pilot study. Addictive Behaviors 34(3): 304-311, 2009. (73 refs.)

We examined the feasibility of brief outpatient detoxification as a treatment for prescription opioid (PO) abusers. Fifteen PO-dependent adults were enrolled to receive buprenorphine stabilization, a 2-week buprenorphine taper, and subsequent naltrexone for those who completed the taper. Subjects also received behavioral therapy, urinalysis monitoring, and double-blind drug administration. Subjects provided 83.8%. 91.7% and 31.2% opioid-negative samples during stabilization. taper and naltrexone phases, respectively. Inspection of individual subject data revealed systematic differences in whether subjects successfully completed the taper without resumption of illicit opioid use. Post-hoc analyses were used to examine the characteristics of subjects who successfully completed the taper (Responders, n = 5 ) vs. those who failed to do so (Nonresponders, n = 9). These pilot data suggest a subset of PO abusers may respond to brief buprenorphine detoxification, though future efforts should aim to improve outcomes, investigate individual differences in treatment response and identify characteristics that may predict those for whom longer-term agonist treatment is warranted.