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CORK Bibliography: Detoxification (Opiates)

63 citations. January 2003 to present

Prepared: January 2008

Ali R; Thomas P; White J; McGregor C; Danz C; Gowing L et al. Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment: determinants of withdrawal severity. Drug and Alcohol Review 22(4): 425-431, 2003. (21 refs.)

This study sought to characterize antagonist-precipitated heroin withdrawal during and immediately following anaesthesia and to identify the determinants of withdrawal severity and duration in 48 dependent heroin users. Objective withdrawal signs decreased significantly with each naloxone bolus administered under anaesthetic. The cost (amount) of the final heroin administration and the number of hours between last heroin use and commencement of anaesthesia were significant, independent predictors of the severity of withdrawal symptomatology. While 83% (40/48) of participants completed withdrawal according to objective criteria and commenced maintenance naltrexone treatment, almost half (22/48) were unable to commence naltrexone on the day of the procedure due to residual withdrawal signs. Fourteen of these 22 participants subsequently commenced naltrexone (median number of days between admission and commencement of naltrexone was 2, range 1 - 6) while eight left treatment prior to initiation of naltrexone. Significantly fewer of those with more severe withdrawal signs during anaesthesia commenced naltrexone (40% vs. 60%). While the severity and duration of withdrawal symptomatology may be moderated by encouraging participants to reduce (or cease) heroin use close to the time of withdrawal, for a substantial proportion of participants in this study, heroin withdrawal by this antagonist-precipitated procedure was neither rapid nor painless.

Amass L; Ling W; Freese TE; Reiber C; Annon JJ; Cohen AJ et al. Bringing buprenorphine-naloxone detoxification to community treatment providers: The NIDA Clinical Trials Network field experience. American Journal on Addictions 13(Supplement 1): S42-S66, 2004. (89 refs.)

In October 2002, the U.S. Food and Drug Administration approved buprenorphine naloxone (Suboxone(R)) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Dials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women mere randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence.

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.

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.

Assadi SM; Hafezi M; Mokri A; Razzaghi EM; Ghaeli P. Opioid detoxification using high doses of buprenorphine in 24 hours: A randomized, double blind, controlled clinical trial. Journal of Substance Abuse Treatment 27(1): 75-82, 2004. (36 refs.)

In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and randomly assigned to two groups in a double blind, parallel trial. Buprenorphine was administered intramuscularly. Twenty patients received 12 mg buprenorphine in 24 h and the remaining 20 patients treated with conventional doses of buprenorphine tapered down over 5 days. Variables that were assessed included retention in treatment, rates of successful detoxification, the Subjective Opiate Withdrawal Scale (OOWS) scores, the Objective Opiate Withdrawal Scale (SOWS) scores, intensity of craving, drug side effects, and levels of hepatic enzymes (ALT and AST). There was no significant difference between the two groups on most variables. The main difference was in the time that maximal withdrawal symptoms occurred, which in the experimental protocol group appeared early while in the conventional protocol group appeared later during the detoxification period. Moreover, the experimental protocol was not only tolerated well but also accompanied with significantly less elevation in the ALT levels compared to the conventional treatment. However, patients in this group used more indomethacin and trazodone for symptom palliation. This study suggests that administration of high doses of buprenorphine in 24 h may be a reasonable approach for shortening of opioid detoxification. However, a larger study to confirm our results is warranted.

Athanasos P; Morrish G; Somogyi AA; Bochner F; White JM. Changes in methadone concentration, opioid effects, and opioid withdrawal during induction onto maintenance treatment. Addictive Disorders and Their Treatment 3(3): 122-132, 2004. (17 refs.)

Objective: Deaths of people on methadone maintenance due to respiratory depression most commonly occur during the first week of dosing. This paper describes the changes in opioid withdrawal, respiratory rate, and pupil diameter that occur during the first 8 days of methadone treatment. The changes in plasma concentration of the active enantiomer, R-methadone, are also described and related to the changes in opioid effects and withdrawal. Methods: Five heroin dependent subjects were assessed each day over the first 8 days of methadone administration. Blood samples were collected and measures made of withdrawal severity, respiration, and pupil diameter prior to methadone dosing and 3 hours after; additional sampling and testing were carried out on days 1, 3, 5, and 8. Blood samples were analyzed to determine the plasma concentration of R-methadone. Results: Over the first 8 days plasma concentration of R-methadone increased, withdrawal severity decreased, and both pupil diameter and respiratory rate decreased. Each of the 3 measures of opioid effect/withdrawal was significantly correlated with plasma R-methadone concentration. Respiratory depression was marked in some subjects and was maximal at time of peak R-methadone concentration. Conclusion: Caution needs to be exercised during the first days of methadone dosing as some degree of respiratory depression is common in non-problematic patients. Observation of patients around time of peak methadone concentration would reduce risk.

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.

Beswick T; Best D; Rees S; Bearn J; Gossop M; Strang J. Major disruptions of sleep during treatment of the opiate withdrawal syndrome: Differences between methadone and lofexidine detoxification treatments. Addiction Biology 8(1): 49-57, 2003. (36 refs.)

Sleep disturbance experienced during methadone or lofexidine opiate detoxification was investigated in 118 opiate-dependent patients receiving inpatient detoxification treatment. Sleep was assessed at four time-points during opiate detoxification using a self-report questionnaire. Maximum sleep disruption occurred at completion of detoxification and during the protracted withdrawal period, with patients in the methadone group reporting higher levels of withdrawal symptoms, lower overall sleep, longer sleep latencies and significantly longer periods of time awake than lofexidine patients. Regression analyses demonstrated a significant relationship between sleep disturbance, protracted withdrawal and retention in treatment, in addition to the major treatment benefit of reduced sleep disturbance conferred by lofexidine treatment.

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.

Cochrane Drugs and Alcohol Group; Gowing L; Ali R; White J. Buprenorphine for the management of opioid withdrawal. (Cochrane Review). IN: Cochrane Library, Volume 1. Software Update: Oxford, 2003. (78 refs.)

Background: Managed withdrawal (detoxification) is a necessary step 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 short-term use of buprenorphine to manage the acute phase of opioid withdrawal. Selection criteria: Randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies that compared different buprenorphine regimes, or that compared buprenorphine with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Data collection and analysis: Potentially relevant studies were assessed for inclusion by one reviewer. Inclusion decisions were confirmed by consultation between reviewers. One reviewer undertook data extraction with the process confirmed by consultation between all three reviewers. Main results: Six studies (5 RCTs and 1 controlled prospective study), involving 357 participants, met the criteria for inclusion in the review. Four studies compared buprenorphine with clonidine. All found withdrawal to be less severe in the buprenorphine treatment group. In three of these studies all participants were withdrawing from heroin. Participants in one study were withdrawing from methadone (10mg/day). Aches, restlessness, yawning, mydriasis, tremor, insomnia, nausea and mild anxiety were reported as being experienced by some participants. Rates of completion of withdrawal ranged from 65% to 100%. None of the studies included in the review reported adverse effects. However a single-group study which therefore did not meet the inclusion criteria, reported the occurrence in some participants of headaches, sedation, nausea, constipation, anxiety, dizziness and itchiness, particularly in the first 2-3 days of treatment. In one of the six studies, and in two studies that did not meet the inclusion criteria, treatment was provided on an outpatient basis. Conclusions: Buprenorphine has potential as a medication to ameliorate the signs and symptoms of withdrawal from heroin, and possibly methadone, but many aspects of treatment protocol and relative effectiveness need to be investigated further.

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; Fisher K; Watson J; Al-Gommer O; McCormick T. The role of detoxification using methadone reduction in a drug treatment service. Journal of Substance Use 8(4): 252-259, 2003. (27 refs.)

Introduction and Methods: Drug treatment services in the UK are currently being encouraged to reduce their waiting lists for treatment. This paper describes the reorganization of the services offered by an inner-city community drug team in order to offer immediate access to detoxification, and so reduce overall waiting times for assessment and treatment. In describing the outcomes of the first year of the service, we aimed to determine the degree of effectiveness of methadone reduction as a detoxification technique, and to highlight some of the sociodemographic and drug-related factors that predict detoxification success. Results: A total of 19 out of 82 (23.2%) participants were opiate-free at the end of the detoxification period, confirmed by both self-report and urinary drug screen. Completion rates were lower for participants opting to continue methadone reduction below 10 mgs per day than for those opting for lofexidine or dihydrocodeine. The rate of reduction of methadone made no difference to the likelihood of completing the detoxification, but being female, having a drug-using partner, having current financial difficulties and committing crime in the month prior to detoxification were predictive of noncompletion of the programme. Conclusions: The reorganization of the service reduced the waiting times for treatment and was acceptable to both participants and staff. Methadone reduction doesn't appear to be the optimum detoxification strategy, and even within a reduction programme of fixed duration there was a tendency for the period of detoxification to become extended.

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.

Fiscella K; Moore A; Engerman J; Meldrum S. Jail management of arrestees/inmates enrolled in community methadone maintenance programs. Journal of Urban Health 81(4): 645-654, 2004. (27 refs.)

Anecdotal evidence suggests that many jails fail to adequately detoxify arrestees/inmates who are enrolled in methadone programs, but there are few empirical data. The objective of this study was to assess bow jails manage arrestees/inmates enrolled in methadone programs. A national survey of 500 jails in the United States was conducted. Surveys were mailed to the 200 largest jails in the country in addition to a random sample of 300 of the remaining jails (10% sample). jails were specifically asked about management of opiate dependency among arrestees/inmates enrolled in methadone programs. Weighted logistic regression analyses were conducted to assess Predictors of continuing methadone during incarceration and use of recommended detoxification protocols. Among the 245 (49%) jails that responded, only 1 in 4 (27%) reported they contacted the methadone programs regarding dose, and only 1 in 8 (12%) continued methadone during the incarceration. Very few (2%) jails used methadone or other opiates for detoxification. Most used clonidine. However, half (48%) of jails failed to use clonidine, methadone, or other opiates to detoxify inmates from methadone. Weighted logistic regression models showed that moderately large jails and those located in the South and Midwest were significantly more likely to continue methadone. Very large jails, those with an estimated prevalence of opiate dependence of 6%-10% among arrestees/inmates, and those located in the Northeast were significantly more likely to use recommended detoxification protocols. Very few jails provided continuous treatment to arrested persons on methadone, and half failed to detoxify arrestees/inmates using recommended protocols. These practices jeopardize the health and wellbeing of persons enrolled in methadone programs and underscore the need for uniform national policies within jails.

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.

Golden SA; Sakhrani DL. Unexpected delirium - During Rapid Opioid Detoxification (ROD). Journal of Addictive Diseases 23(1): 65-75, 2004. (15 refs.)

Rapid Opioid Detoxification (ROD), using a combination of the long acting opioid antagonist, Naltrexone and the alpha 2 agonist Clonidine, is a method to detoxify patients who are opioid dependent. The daily administration of Naltrexone in increasing dosages decreases the duration of the withdrawal syndrome associated with opioids, especially longer acting drugs such as Methadone. This study is intended to report the frequency of delirium, as defined in DSM IV, during the ROD of Methadone maintained patients. A chart review was conducted of twenty consecutive patients who received in-patient ROD from Methadone maintenance from January 1999 to December 1999. Methadone was tapered and discontinued prior to ROD and Naltrexone was administered in increasing daily doses. Five individuals developed delirium and discontinued the procedure on the first day, fourteen patients completed the protocol, and one dropped out prior to completion. A significant incidence of delirium resulted from the ROD procedure.

Gonzalez G; Oliveto A; Kosten TR. Combating opiate dependence: A comparison among the available pharmacological options. (review). Expert Opinion on Pharmacotherapy 5(4): 713-725, 2004. (133 refs.)

Pharmacotherapies for heroin addiction may target opiate withdrawal symptoms, facilitate initiation of abstinence and/or reduce relapse to heroin use either by maintenance on an agonist or antagonist agent. Available agents include opioid agonists, partial opioid agonists, opioid antagonists and alpha(2)-agonists for use during managed withdrawal and long-term maintenance. Experimental approaches combine alpha(2)-agonists with naltrexone to reduce the time of opiate withdrawal and to accelerate the transition to abstinence. Recently, buprenorphine has been introduced in the US for off ice-based maintenance, with the hope of replicating the success of this treatment in Europe and Australia. Naloxone has been added to buprenorphine in order to reduce its potential diversion to intravenous use, whilst facilitating the expansion of treatment. Although comprehensive substance abuse treatment is not limited to pharmacotherapy, this review will focus on the rationale, indications and limitations of the range of existing medications for detoxification and relapse prevention treatments. The two major goals of pharmacotherapy are to relieve the severity of opiate withdrawal symptoms during the managed withdrawal of the opioid and to prevent relapse to heroin use either after abstinence initiation or after being stabilised on a long-acting opiate agonist, such as methadone.

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.

Gowing L; Ali R; White J. Opioid antagonists with minimal sedation for opioid withdrawal. (Cochrane Review). IN: Cochrane Library, Volume 1. Update Software: Oxford, 2003. (69 refs.)

Background: Managed 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. Objectives: To assess the effectiveness of interventions involving opioid antagonists to induce withdrawal, in combination with medication to ameliorate symptoms but with minimal sedation. Search strategy: Multiple databases were searched using a strategy designed to retrieve references broadly addressing opioid withdrawal. Reference lists of retrieved studies, reviews and conference abstracts were handsearched. Selection criteria: Randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies that compared antagonist-induced (conscious) withdrawal with other approaches to modify the signs and symptoms of withdrawal in opioid-dependent participants. Data collection and analysis: One reviewer assessed potentially relevant studies for inclusion and undertook data extraction. All inclusion decisions and the overall process were confirmed by consultation between all reviewers. Main results: Ten studies (5 randomised and 5 non-randomised controlled trials), involving 770 participants, met the inclusion criteria for the review. Treatment regimes using opioid antagonists to induce withdrawal, with minimal sedation, varied in a number of aspects preventing description of a "standard" approach. Antagonist-induced withdrawal is associated with similar or less overall severity than withdrawal managed primarily with an alpha2 adrenergic agonist. This is probably because of earlier resolution of withdrawal. Peak severity is likely to be higher with antagonist-induced withdrawal and require the use of additional adjunct medications. Withdrawal from methadone may be more severe than withdrawal from heroin, but data are limited. Antagonist-induced withdrawal appears to be associated with somewhat higher rates of completion of withdrawal and achievement of maintenance doses of naltrexone but there were insufficient data for statistical analyses. The benefit of higher rates of completion of withdrawal is lessened by apparently low rates of retention in subsequent naltrexone maintenance treatment. Conclusions: The use of opioid antagonists combined with alpha2 adrenergic agonists is feasible and probably increases the likelihood of transfer to naltrexone compared to 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; Farrell M; Ali R; White J. Alpha2 adrenergic agonists for the management of opioid withdrawal. IN: Cochrane Library, Volume 1. Software Update: Oxford, 2003. (119 refs.)

Background: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term 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 use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine) to manage the acute phase of opioid withdrawal. Search strategy: Multiple electronic databases (including MEDLINE, EMBASE, PsycINFO, Australian Medical Index, Cochrane Clinical Trials Register) were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted. Selection criteria: Controlled trials comparing alpha2 adrenergic agonists with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2 adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Data collection and analysis: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers. Main results: Twenty-two studies, involving 1691 participants, were included. Eighteen were randomised controlled trials; for the remaining studies allocation was by participant choice in one, another used alternate allocation and in two the method of allocation was unclear. Eleven studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. For the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, there were insufficient data for statistical analysis, but withdrawal intensity appears similar to, or marginally greater with alpha2 adrenergic agonists, while signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. No significant difference was detected in rates of completion of withdrawal with adrenergic agonists compared to reducing doses of methadone, or clonidine compared to lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. Conclusions: No significant difference in efficacy was detected for treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, for the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than clonidine. There are insufficient data available to support a conclusion on the efficacy of other alpha2 adrenergic agonists.

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.

Jackson L; Ting A; Mckay S; Galea P; Skeoch C. A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome. Archives of Disease in Childhood 89(4 Special Issue): F300-F304, 2004. (26 refs.)

Background: The incidence of neonatal abstinence syndrome (NAS) has increased 10-fold over the last decade in Glasgow. In the Princess Royal Maternity Hospital, it now accounts for 17% of special care baby unit (SCBU) admissions. Objective: To compare opiate replacement therapy (morphine sulphate) with the present standard treatment (phenobarbitone) for management of NAS. The primary study end point was duration of pharmaceutical treatment. Secondary end points were the requirement for additional drugs and the requirement for SCBU admission. Design: Double blind, randomised controlled clinical trial. Methods: Differential diagnoses were excluded, and two consecutive Lipsitz scores. 4 defined NAS requiring treatment. Infants were randomised to receive morphine sulphate or phenobarbitone. Treatments were identical in appearance, odour, and volume. Increments, decrements, and discontinuation of treatments were protocol driven. Results: Seventy five infants participated. All mothers received opiate replacement therapy (methadone) during pregnancy and most used other drugs (n = 62, 83%). No significant difference in maternal drug use patterns was observed between treatment groups. Median treatment duration was four days shorter with opiate replacement (8 v 12 days, Mann-Whitney U test, p = 0.02). Phenobarbitone treated infants tended to require second line treatment (47% v 35%, chi(2) test, p = 0.11) and SCBU admission (62% v 30%, chi(2) test, p = 0.04) more often. Conclusions: Opiate replacement therapy appears to be superior for management of symptomatic NAS when maternal opiate use is prevalent. The shorter treatment duration and lower requirement for higher intensity nursing may have significant cost implications. Tailoring NAS treatment to local maternal drug use may result in similar benefits.

Johnson TS; Carr M. Naltrexone-mediated opiate detoxification: A matter of terminology! (editorial). Addiction Biology 8(3): 267-269, 2003. (12 refs.)

Kaye AD; Gevirtz C; Bosscher HA; Duke JB; Frost EAM; Richards TA et al. Ultrarapid opiate detoxification: A review. Canadian Journal of Anaesthesia 50(7): 663-671, 2003. (60 refs.)

Purpose: This review on ultrarapid detoxification examines the pharmacology, techniques, and efficacy of this potentially promising technique and contrasts it with conventional treatment modalities. Source: The information found here is derived from experiences at the Texas Tech University, government reports, and peer reviewed journals. Principal findings: Incidence and prevalence of heroin use is on the rise. Social and treatment costs suggest that this problem is staggering. Approximately 400,000 patients are enrolled in or are actively seeking methadone therapy. While many of these individuals want to undergo detoxification, traditional techniques, including methadone tapering are usually unsuccessful. The withdrawal syndrome is extremely unpleasant, may be fatal, and deters patients from completing the detoxification process, Ultrarapid detoxification entails general anesthesia in conjunction with large boluses of narcotic antagonists. This combination allows the individual to completely withdraw from the opiate without suffering the discomfort of the withdrawal syndrome. Unless performed properly, this procedure can be dangerous due to the sympathetic outflow. However, with proper support, this danger can be mitigated. Conclusion: Ultrarapid opiate detoxification, performed under the proper circumstances, is associated with few adverse events and is relatively comfortable for patients who seek treatment for their addiction.

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.

Krabbe PFM; Koning JPF; Heinen N; Laheij RJF; Van Cauter RMV; De Jong CAJ. Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: Abstinence rates and withdrawal distress experiences. Addiction Biology 8(3): 351-358, 2003. (29 refs.)

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p<0.01) and 2 months (RD-GA 93% vs. SMT 33%, p<0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.

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.

Lintzeris N; Bammer G; Rushworth L; Jolley DJ; Whelan G. Buprenorphine dosing regime for inpatient heroin withdrawal: a symptom-triggered dose titration study. Drug and Alcohol Dependence 70(3): 287-294, 2003. (32 refs.)

The study aimed to identify the range of buprenorphine doses required to comfortably alleviate symptoms in patients undergoing inpatient heroin withdrawal using a symptom-triggered titration dosing regime, and to identify the patient characteristics that impact upon the buprenorphine dose requirements. The study was conducted in two Australian inpatient withdrawal units, recruiting 63 dependent, injecting heroin users with no recent methadone treatment, dependence on other drugs, or other active medical or psychiatric conditions. In a single (patient) blinded case series, placebo or 2 mg sublingual buprenorphine tablets was administered four times a day according to severity of withdrawal (assessed with Subjective Opiate Withdrawal Scale). Up to 16 mg buprenorphine was available over the first 4 days of the admission, up to 8 mg on day 5, and placebo continued until day 6. Thirty-two subjects completed the dosing regime, with mean (plus or minusS.D.) daily doses of 3.8plus or minus2.8 on day 1, 5.8plus or minus3.2 on day 2, 4.8plus or minus3.3 on day 3, 2.3plus or minus2.6 on day 4, 0.8plus or minus1.3 on day 5, and a total dose of 17.4plus or minus9.7. Higher buprenorphine doses were required by those patients with more severe psychosocial dysfunction, women, those with more frequent heroin use, and those with more severe dependence on heroin at intake. A dosing regime using sublingual buprenorphine tablets for short inpatient heroin withdrawal is proposed.

Lintzeris N; Ritter A; Panjari M; Clark N; Kutin J; Bammer G. Implementing buprenorphine treatment in community settings in Australia: Experiences from the buprenorphine implementation trial. American Journal on Addictions 13(Supplement 1): S29-S41, 2004. (22 refs.)

Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed.

Luty J; Nikolaou V; Bearn J. Is opiate detoxification unsafe in pregnancy? Journal of Substance Abuse Treatment 24(4): 363-367, 2003. (18 refs.)

Despite the widespread avoidance of detoxification in the second or third trimesters, there is no clear evidence to support the view that methadone withdrawal is harmful in pregnant opiate dependent women. We investigated the safety of methadone detoxification in pregnancy in a retrospective case series of 101 pregnant opiate dependent women who underwent a 21-day in-patient methadone withdrawal. One miscarriage occurred in the first trimester (n = 5; incidence rate ratio of 6.87 compared to population norms (95% CI = 0.16-47.3; p = .15)). No miscarriages were observed in the second trimester (n = 54; incidence rate RATIO = 0 compared to population norms (95% CI = 0-3.69; p = .27). One premature delivery occurred in the third trimester (1 in 158 weeks at risk compared to 1 in 150 weeks in population norms; p = .16). Methadone detoxification treatment was not associated with any increased risk of miscarriage in the second trimester or premature delivery in the third trimester.

Mannelli P; Gottheil E; Buonanno A; De Risio S. Use of very low-dose naltrexone during opiate detoxification. Journal of Addictive Diseases 22(2): 63-70, 2003. (15 refs.)

The use of antagonist drugs to reduce the duration of opiate detoxification severely enhances withdrawal symptoms. To investigate the feasibility of administering antagonists with opiates without intense withdrawal during detoxification, 5 methadone maintained patients were evaluated while tapering methadone and receiving at the same time very low (0.125 mg), then increasing daily doses of naltrexone in the course of a 6-day, day hospital treatment. Reduced quantities of adjunctive medications were administered, as compared to the standard protocols, the treatment was completed without incidents or particular discomfort and all patients were easily induced to naltrexone maintenance by the day of discharge. Controlled studies will clarify whether very low-dose naltrexone provides a safe and comfortable detoxification technique to reduce withdrawal intensity and duration without the problems of heavy sedation, as suggested by the description of these clinical cases.

Martinez-Raga J; Sabater A; Perez-Galvez B; Castellano M; Cervera G. Add-on gabapentin in the treatment of opiate withdrawal. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 28(3): 599-601, 2004. (15 refs.)

Gabapentin is an antiepileptic drug shown to be effective in the treatment of pain disorders and appears to be useful as well for several psychiatric disorders, including bipolar disorder, anxiety disorders, alcohol withdrawal and cocaine dependence. Gabapentin, at a dose of 600 mg three times a day, was evaluated as an add-on medication to a standard detoxification regime in seven heroin dependent individuals undergoing outpatient opiate withdrawal treatment. All seven patients successfully completed opiate detoxification and commenced opiate antagonist treatment with naltrexone on day five of withdrawal treatment, as scheduled. No adverse event was noted. Gabapentin appeared to lead a reduction in symptomatic medication and an overall beneficial effect on symptoms of heroin withdrawal.

Masson CL; Barnett PG; Sees KL; Delucchi KL; Rosen A; Wong W et al. Cost and cost-effectiveness of standard methadone maintenance treatment compared to enriched 180-day methadone detoxification. Addiction 99(6): 718-726, 2004. (32 refs.)

Aims: To compare the cost and cost-effectiveness of methadone maintenance treatment and 180-day methadone detoxification enriched with psychosocial services. Design: Randomized controlled study conducted from May 1995 to April 1999. Setting: Research clinic in an established drug treatment program. Participants One hundred and seventy-nine adults with diagnosed opioid dependence. Intervention Patients were randomized to methadone maintenance (n = 91), which required monthly 1 hour/week of psychosocial therapy during the first 6 months or 180-day detoxification (n = 88), which required 3 hours/week of psychosocial therapy and 14 education sessions during the first 6 months. Measurements: Total health-care costs and self-reported injection drug use. A two-state Markov model was used to estimate quality-adjusted years of survival. Findings: Methadone maintenance produced significantly greater reductions in illicit opioid use than 180-day detoxification during the last 6 months of treatment. Total health-care costs were greater for maintenance than detoxification treatment ($7564 versus $6687; P < 0.001).Although study costs were significantly higher for methadone maintenance than detoxification patients ($4739 versus $2855, P < 0.001), detoxification patients incurred significantly higher costs for substance abuse and mental health care received outside the study. Methadone maintenance may provide a modest survival advantage compared with detoxification. The cost per life-year gained is $16,967. Sensitivity analysis revealed a cost-effectiveness ratio of less than $20, 000 per quality-adjusted life-year over a wide range of modeling assumptions. Conclusions Compared with enriched detoxification services, methadone maintenance is more effective than enriched detoxification services with a cost-effectiveness ratio within the range of many accepted medical interventions and may provide a survival advantage. Results provide additional support for the use of sustained methadone therapy as opposed to detoxification for treating opioid addiction.

McNicholas L. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) 40. Rockville MD: Center for Substance Abuse Treatment, 2004. (181 report refs.)

The goal of this TIP is to provide physicians with information needed to make practical and informed decisions about the use of buprenorphine in treating opioid addiction. These guidelines address the pharmacology and physiology of opioids, opioid addiction, and treatment with buprenorphine; describe patient assessment and the choice of opioid addiction treatment options; provide detailed treatment protocols for opioid withdrawal and maintenance therapy with buprenorphine; and include information on the treatment of special populations, e.g., pregnant women, adolescents, and polysubstance users. Federal statute, the Drug Addiction Treatment Act of 2000 (DATA 2000), established a new approach for the medication-assisted treatment of opioid addiction in the United States. Prior to that the use of opioid medications to treat opioid addiction was permissible only in federally approved Opioid Treatment Programs (OTPs) (i.e., methadone clinics). Now, under the provisions of this Act qualifying physicians in the medical office and other appropriate settings outside the OTP system may prescribe and/or dispense Schedule III, IV, and V opioid medications for the treatment of opioid addiction if they have been approved by the Food and Drug Administration for that purpose. This TIP is organized into 6 chapters and 10 appendices. Chapter 1, Introduction, describes the basic facts regarding opioid addiction, the traditional approaches to its treatment, and the new DATA 2000 treatment paradigm. Chapter 2, Pharmacology, addresses, the physiology and pharmacology of opioids in general, and of buprenorphine in particular. The chapter also provides a review of the research literature regarding the safety and effectiveness of buprenorphine for the treatment of opioid addiction. Chapter 3, Patient Assessment, summarizes an approach to screening and assessment of individuals who are addicted to opioids and who may be candidates for treatment with buprenorphine. Chapter 4, Treatment Protocols, provides detailed protocols on the use of buprenorphine for the treatment of opioid addiction, including both maintenance and withdrawal treatment approaches. Chapter 5, Special Populations, discusses several special populations whose circumstances require careful consideration as they begin buprenorphine treatment. Treating these special populations requires an understanding of available resources and often involves collaboration with specialists in other areas of care. Chapter 6, Policies and Procedures, discusses legal and regulatory issues pertaining to the provision of opioid addiction treatment, including the procedures and physician qualifications necessary to obtain the required waiver under DATA 2000 to provide office -based opioid addiction treatment, recommended office practice policies and procedures, the security and confidentiality of opioid addiction care information, and the use of buprenorphine in OTPs.

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.

Prieto IJ; Poyo-Guerrero R; Fernandez R; Ochoa E. Ultrarapid high-dose methadone detoxification. (letter). Psychopharmacology 165(4): 430-430, 2003. (5 refs.)

Briefly discusses the authors' protocol of ultrarapid heroin detoxification based on the techniques of T. O. Seoane et al (1997) and O. Presslich and N. Loimer (1989). The procedure used in heroin addicts requires propofol, clonidine, and naltrexone and has a higher rate of complications in high dose methadone patients who show more, and more severe withdrawal symptoms. The results of a recently initiated, modified, ultrarapid method of opiate detoxification is discussed for use in patients taking high doses of methadone.

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. Perspectives of opiate detoxification treatment. IN: Kuntze MF; Muller-Spahn F; Ladewig D; Bullinger AH, eds. Basic and Clinical Science of Opioid Addiction. Bibliotheca psychiatrica, no. 170. Basel Switzerland: Karger, 2003. pp. 20-24. (13 refs.)

This chapter provides a perspective on opiate detoxification. It begins with a discussion of the goals of detoxification, which are seen as alleviation of withdrawal symptoms, prevention of complication, diagnosis and treatment of comorbid somatic and psychiatric disorders, and referral to abstinence-oriented treatment. Detoxification is not seen as an end in itself, but as a necessary element in providing extended treatment. Attention is then directed to alternative strategies for accomplishing opiate detoxification. Inasmuch as half of all opiate addicts drop out of detox prematurely, this is seen as suggesting that new medical strategies are required to reduce the intensity and/or length of withdrawal. Among some of the newer approaches described and used in the author's clinical is ultra-rapid detoxification. This "pushes" opiate drug molecules from receptor sites through administration of opiate antagonists, and is conducted under anesthesia. The possibility of alternative settings for opiate detoxification are also discussed.

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.

Siddappa R; Fletcher JE; Heard AMB; Kielma D; Cimino M; Heard CMB. Methadone dosage for prevention of opioid withdrawal in children. Paediatric Anaesthesia 13(9): 805-810, 2003. (17 refs.)

Background: Opioids are frequently used for sedation in the Paediatric Intensive Care Unit (PICU). With time the dosing often increases because of tolerance. On cessation of the sedation there is a risk of the opioid withdrawal syndrome. The aim of our study was to evaluate methadone dosing as a risk factor for opioid withdrawal and to determine optimal dose and efficacy of methadone to prevent withdrawal. Method: We undertook a clinical, retrospective, chart review study. Data were analysed from the quality improvement initiative database of a tertiary-care 18 bed PICU. Results: Data from 30 children who received an opioid infusion for greater than or equal to7 days and subsequently received methadone for opioid withdrawal (between January 2000 and July 2001) were analysed. Nurses documented the presence or absence of withdrawal signs daily. Our unit protocol has recommended converting the patient's opioid dose into fentanyl equivalents and a dose of methadone equal to the total daily dose of fentanyl to be given three times a day. Twenty patients had no or minimal withdrawal symptoms and 10 experienced significant withdrawal. Age, weight, PRISM score, lorazepam dose, muscle relaxant use and fentanyl dose were not statistically significantly between these groups. Receiver Operator Characteristics analysis showed that 80% of the suggested methadone dose was effective in minimizing withdrawal symptoms. The odds ratio for withdrawal with <80% of the predicted methadone dose was 21. Conclusions: Inadequate methadone is a risk factor for opioid withdrawal. A daily starting methadone dose equivalent to 2.5 times the daily fentanyl dose is effective in minimizing withdrawal symptoms.

Sobel BFX; Sigmon SC; Walsh SL; Johnson RE; Liebson IA; Nuwayser ES; Kerrigan JH; Bigelow GE. Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification. Drug and Alcohol Dependence 73(1): 11-22, 2004. (51 refs.)

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety and pharmacokinetics of a single-dose buprenorphine depot in physically dependent opioid abusers. The present study also examined the efficacy of depot buprenorphine in suppressing symptoms of opioid withdrawal, attenuating the effects of exogenous opioid challenge, and providing clinical detoxification. Five opioid-dependent volunteers each received a single subcutaneous depot injection containing 58 mg of buprenorphine and were assessed for at least four weeks for signs and symptoms of opioid withdrawal, first residentially and then as outpatients. Depot buprenorphine appeared to provide effective relief from opioid withdrawal, with no participant requiring additional medication for withdrawal relief following depot administration. The depot was safe and well-tolerated, with no significant side effects, signs of intoxication, or respiratory depression. In the opioid challenge sessions, depot buprenorphine appeared to produce substantial opioid blockade that persisted for 6 weeks post-depot administration. Results from the present study suggest that depot buprenorphine offers significant promise for enhancing the delivery of effective opioid agonist treatment while minimizing risk for abuse of the medication.

Sobey PW; Parran TV; Grey SF; Adelman CL; Yu J. The use of tramadol for acute heroin withdrawal: A comparison to clonidine. Journal of Addictive Diseases 22(4): 13-25, 2003. (40 refs.)

Using a retrospective chart review, 59 patients detoxified with tramadol were compared to 85 patients detoxified with clonidine on rates of leaving against medical advice (AMA) and control of withdrawal symptoms. Patients detoxified with tramadol had 23% (95% Cl, 0.09-0.59; P < .01) the risk of leaving AMA and scored an average of 0.24 points lower (95% CI, 0.08-0.41; P < .01) on a 0-3 point withdrawal symptom scale compared to patients detoxified with clonidine. This preliminary study indicates that tramadol is more effective in managing withdrawal than clonidine, and may be especially useful in outpatient detoxification.

Strobbe S; Brower KJ; Galen LW. Predicting completion of outpatient opioid detoxification with clonidine. American Journal on Addictions 12(3): 260-269, 2003. (22 refs.)

Completion rates for outpatient opioid detoxification with clonidine generally range from 20-40%, but few studies have examined the correlates of successful completion. Of 29 consecutive patients, we compared those who completed detoxification with clonidine (n = 12) to those who did not (n = 17). Patients who completed treatment were significantly (p < 0.05) more likely to depend on opioids other than heroin, have private health insurance, and report low levels of subjective withdrawal symptoms. Patients with two or three of these characteristics were about seven times more likely to complete treatment than patients with none or one. Although it may not detoxify most opioid-dependent patients, clonidine will likely play a continued role in selected patients when a non-narcotic agent is desirable. The study findings may help target patients who could benefit the most from outpatient clonidine detoxification.

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.

Tamaskar R; Parran TV; Heggi A; Brateanu A; Rabb M; Yu J. Tramadol versus buprenorphine for the treatment of opiate withdrawal: A retrospective cohort control study. Journal of Addictive Diseases 22(4): 5-12, 2003. (24 refs.)

Various drugs have been used for the treatment of opioid withdrawal, e.g., methadone, buprenorphine, and clonidine. Tramadol is a centrally acting synthetic analgesic agent with opiate activity due to low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M I to V opioid receptors. As a consequence, there may be a role for the use of tramadol in the treatment of opiate withdrawal. We attempt to assess the efficacy of tramadol in treating moderate heroin withdrawal through a retrospective cohort control study, conducted in a detoxification unit in a community teaching hospital. Out of 100 heroin abusers admitted for detoxification during the review period, 64 patients who were treated either with buprenorphine or tramadol, were included in this study, with 20 participants in the buprenorphine group and 44 in the tramadol group. Both groups were matched for age, sex, and self-reported average quantity of heroin used per day. In the tramadol group, the average CINA maximum was 9.0, and in the buprenorphine group it was 11.2 (P = 0.07). The use of oral clonidine per patient in the tramadol group was 1.6 tablets, and in the buprenorphine group 0.1 tablets (P = 0.002). The length of stay was 3.7 days in the tramadol group and 4.1 days in the buprenorphine group (P = 0.5). Four participants in the tramadol group received three or more doses of buprenorphine because their symptoms were not controlled, and were considered as treatment failures. These preliminary data suggest that tramadol may be comparable to buprenorphine in the management of mild to moderately severe heroin withdrawal. These findings, if reproduced in-larger studies with stronger research designs, have potentially great implications for the, management of opioid withdrawal in both the inpatient and outpatient setting.

Umbricht A; Hoover DR; Tucker MJ; Leslie JM; Chaisson RE; Preston KL. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. Drug and Alcohol Dependence 69(3): 263-272, 2003. (32 refs.)

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

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.

Zullino DF; Krenz S; Favrat B; Zimmermann G; Bertschy G; Besson J. The efficiency of a carbamazepine-mianserin combination scheme in opiate detoxification. Human Psychopharmacology: Clinical and Experimental 19(6): 425-430, 2004. (50 refs.)

A recent comparative randomized double-blind study has suggested the utility of a carbamazepine/mianserin combination as a treatment for opiate withdrawal. The aim of the present study was to explore the feasibility and efficiency of this combination under naturalistic conditions. Five hundred and fifty mostly polysubstance abusing patients treated with a standardized scheme combining carbamazepine and mianserin were assessed with regard to deviations to the protocol, used comedications and retention in treatment. Three hundred and sixty three patients (66.0%) received the carbamazepine/mianserin combination as specified by the standardized protocol. In 350 patients (63.7%) the whole 10 days was completed. The most frequently used p.r.n. medications were for anxiety (47.5%) and insomnia (54.5%). The treatment of opiate withdrawal with a carbamazepine/mianserin combination scheme in an inpatient setting seems to be feasible and applicable with few adaptations to most patients, and may represent an interesting treatment option for multidrug users.