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CORK Bibliography: Detoxification (Opiates)

32 citations. January 2009 to present

Prepared: December 2011

Amato L; Minozzi S; Davoli M; Vecchi S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. (review). Cochrane Database of Systematic Reviews 9: article -CD005031, 2011. (85 refs.)

Background: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome. Objectives: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status. Search strategy We searched the Cochrane Drugs and Alcohol Group trials register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 6, 2011), PUBMED (1996 to June 2011); EMBASE (January 1980 to June 2011); CINAHL (January 2003 to June 2008); PsycINFO (1985 to April 2003) and reference list of articles. Selection criteria: Randomised controlled trials and controlled clinical trial which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded. Data collection and analysis: Two authors independently assessed trials quality and extracted data. Main results: Eleven studies, 1592 participants, fulfilled the criteria of inclusion and were included in the review. The studies considered five different psychosocial interventions and two pharmacological treatments (methadone and buprenorphine). Compared to any pharmacological treatment alone, the association of any psychosocial with any pharmacological was shown to significantly reduce dropouts RR 0.71 (95% CI 0.59 to 0.85), use of opiate during the treatment, RR 0.82 (95% CI 0.71 to 0.93), at follow up RR 0.66 (95% IC 0.53 to 0.82) and clinical absences during the treatment RR 0.48 (95%CI 0.38 to 0.59). Moreover, with the evidence currently available, there are no data supporting a single psychosocial approach. Authors' conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, participants abstinent at follow-up and clinical attendance. The evidence produced by this review is limited due to the small number of participants included in the studies, the heterogeneity of the assessment or the lack of detailed outcome information that prevented the possibility of cumulative analysis for several outcomes. Nevertheless it seems desirable to develop adjunct psychosocial approaches that might make detoxification more effective.

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

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

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

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

Benich JJ. Opioid dependence. Primary Care 38(1): 59+, 2011. (56 refs.)

Opioid dependence is becoming a more common problem in the United States that gives rise to many negative health and social consequences for both individuals and society as a whole. Opioid dependence presents a challenging issue for physicians to identify and treat. Understanding and managing withdrawal symptoms is often a necessary first step on the road to recovery for these patients. Long-term therapy options include detoxification, nonpharmacologic treatment plans, and maintenance replacement treatment with either methadone or buprenorphine. Physicians meeting necessary requirements have the option of implementing office-based opioid-assisted maintenance therapy.

Dijkstra BAG; De Jong CAJ; Wensing M; Krabbe PFM; van der Staak CPF. Opioid detoxification: From controlled clinical trial to clinical practice. American Journal on Addictions 19(3): 283-290, 2010. (33 refs.)

Controlled clinical trials have high internal validity but suffer from difficulties in external validity. This study evaluates the generalizability of the results of a controlled clinical trial on rapid detoxification in the everyday clinical practice of two addiction treatment centers. The results show that rapid detoxification in everyday practice differs with regard to patient characteristics, enrolment, and completion rates (86.8% vs. 100%). However, abstinence rates after rapid detoxification in the controlled clinical trial (61.8%) were generalizable to everyday clinical practice (59.0%). Implementation factors that may have influenced the results, such as referral problems and treatment delivery, are discussed.

Finnegan L; Pacini M; Maremmani I. Methadone treatment for pregnant heroin addicted women. Heroin Addiction and Related Clinical Problems 12(2): 29-35, 2010. (71 refs.)

A review of methadone-related issues and the approach to heroin addicted patients is presented with the aim to clarify what is practiced by the establishment of anti-craving treatment and what is expected within a history of addiction. A series of clinical situations occurring throughout pregnancy to early child development are described, and the etiological hypothesis discussed. Moreover, some methodological considerations are described in order to better understand some ambiguity about the effectiveness and harmlessness of methadone treatment, particularly with regard to neonatal opiate withdrawal. Limitations to the outcome of pregnancies in heroin addicted women seems to be due to misconceptions about methadone toxicity and neonatal damage, which may lead to the mishandling of methadone as a therapeutic modality, especially with regard to maintenance at effective dosages.

Geng LN; Qian BJ. Implicit and explicit cognition of Chinese heroin abusers. Social Behavior and Personality 39(4): 433-443, 2011. (25 refs.)

Sixty-five heroin abusers receiving Methadone Maintenance Treatment (MMT), 38 heroin abusers not receiving MMT, and 30 nonusers of drugs participated in this investigation of cognition in heroin and methadone users. Heroin users were measured for both implicit and explicit cognition, while the control group of nonusers was measured only for implicit cognition. The results demonstrate that implicit cognition can influence the development of addictive behaviors, and that implicit and explicit cognition of heroin were separate and independent constructs. Based on the results of Implicit Association Tests (IAT; Greenwald, McGhee, & Schwartz, 1998) MMT appears to be a valid method for opiate withdrawal treatment as it reverses the implicit desire for heroin in heroin abusers.

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

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

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

Back ground: Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of long-term substitution treatment. Objectives: To assess the effectiveness of opioid antagonists in combination with minimal sedation to manage opioid withdrawal. Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966-July 2008), EMBASE (January 1985-2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles. Selection criteria Controlled studies of interventions involving the use of opioid antagonists in combination with minimal sedation to manage withdrawal in opioid-dependent participants compared with other approaches or different opioid antagonist regimes. Data collection and analysis: One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors. Main results: Nine studies (6 randomised controlled trials), involving 837 participants, met the inclusion criteria for the review. The quality of the evidence is low, but suggests that withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, while the overall severity is less. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone). In some situations antagonist-induced withdrawal may be associated with significantly higher rates of completion of treatment, comp[ared to withdrawal managed primarily with adrenergic agonists. However, this outcome has not been produced consistently, and the extent of any benefit is highly uncertain. Authors' conclusions: The use of opioid antagonists combined with alpha(2)-adrenergic agonists is a feasible approach to the management of opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist. A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium. Further research is required to confirm the relative effectiveness of antagonist-induced regimes, as well as variables influencing the severity of withdrawal, adverse effects, the most effective antagonist-based treatment regime, and approaches that might increase retention in subsequent naltrexone maintenance treatment.

Heslin KC; Stein JA; Heinzerling KG; Pan DY; Magladry C; Hays RD. Clinical correlates of health-related quality of life among opioid-dependent patients. Quality of Life Research 20(8): 1205-1213, 2011. (49 refs.)

Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services. We tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users in a clinical trial. Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, we tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36. Most hypothesized relationships were significant, and model fit was good. The model explained 36% of the variance in mental HRQOL and 34% of the variance in physical HRQOL. The conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Analysis of longitudinal data would help to evaluate more rigorously the adequacy of the model for explaining HRQOL in opioid withdrawal.

Katz EC; Brown BS; Schwartz RP; O'Grady KE; King SD; Gandhi D. Transitioning opioid-dependent patients from detoxification to long-term treatment: Efficacy of intensive role induction. Drug and Alcohol Dependence 117(1): 24-30, 2011. (31 refs.)

Despite findings that opioid detoxification serves little more than a palliative function. few. patients who enter detoxification subsequently transition to long-term treatment. The current study evaluated intensive role induction (IRI), a strategy adapted from a single-session intervention previously shown to facilitate engagement of substance-dependent patients in drug-free treatment. IRI was delivered either alone or combined with case management (IRI + CM) to determine the capacity of each condition to enhance transition and engagement in long-term treatment of detoxification patients. Study participants were 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. Following clinic intake, participants were randomly assigned to IRI, IRI + CM, or standard clinic treatment (ST). Outcomes were assessed in terms of adherence and satisfaction with the detoxification program, detoxification completion, and transition and retention in treatment following detoxification. Participants who received IRI and IRI + CM attended more counseling sessions during detoxification than those who received ST (both ps < .001). IRI, but not IRI + CM participants, were more likely to complete detoxification (p = .017), rated their counselors more favorably (p = .01), and were retained in long-term treatment for more days following detoxification (p = .005), than ST participants. The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.

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

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

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

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

Maani CV; DeSocio PA; Jansen RK; Merrell JD; McGhee LL; Young A et al. Use of ultra rapid opioid detoxification in the treatment of us military burn casualties. Journal of Trauma, Injury, Infection and Critical Care 71(supplement 1): S114-S119, 2011. (18 refs.)

Background: The purpose of this case series was to review the management of burn patients who requested ultrarapid opioid detoxification under anesthesia after extended duration of narcotic use for chronic pain related to burn injury. Methods: The treatment plan of six opioid-dependent burn patients was analyzed to assess the effectiveness of our detoxification practice to date. Demographic and clinical information was used to characterize the patient population served: age, burn size, injury severity, duration of narcotic use before detoxification intervention, and length of hospitalization stay. Daily narcotic consumption, in morphine equivalent units, was noted both before and after detoxification. Results: Six burn patients (average age, 31 years) underwent detoxification at the Burn Center during a hospitalization lasting between 1 day and 2 days. Average burn size was 38% total body surface area (range, 17-65); average Injury Severity Score was 30 (range, 25-38). Mean duration of narcotic use was 672 days (range, 239-1,156 days); average use of narcotics at time of detoxification was >200 units daily. Mean outpatient consumption for opioids after the intervention was minimal (<25 units/d). No complications were noted during any procedures. Conclusions: The results of ultrarapid opioid detoxification under anesthesia suggests that it is safe and effective for treating opioid addiction in military burn casualties when a coordinated, multidisciplinary approach is used. Safety and effectiveness to date validate current practice and supports incorporation into clinical practice guidelines. Further clinical research is warranted to identify those patients who may benefit most from detoxification and to determine the timing of such treatment.

Mactier H. The management of heroin misuse in pregnancy: Time for a rethink? (review). Archives of Disease in Childhood. Fetal and Neonatal Edition 96(6): F457-F460, 2011. (42 refs.)

Heroin use in pregnancy is a worldwide problem. Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK. There is, however, increasing evidence of adverse effects upon developing cortical and visual function in children of treated heroin-addicted mothers. The longer-term implications of this are not yet clear, and are confounded by poly-drug misuse and ongoing social deprivation. There is a paucity of evidence regarding outcome for infants who require pharmacological treatment for neonatal abstinence syndrome compared to those who have only mild symptoms. Well-controlled studies of the treatment of heroin misuse in pregnancy that take account of both neonatal and longer term outcomes for the child are urgently required.

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

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

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

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

Mannelli P; Peindl K; Patkar AA; Wu LT; Tharwani HM; Gorelick DA. Problem drinking and low-dose naltrexone-assisted opioid detoxification. Journal of Studies on Alcohol and Drugs 72(3): 507- 513, 2011. (42 refs.)

Objective: The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Method: Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and self-report. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Results: Problem drinking opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p =.001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Conclusions: Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.

McWhirter L; Morris S. A case report of inpatient detoxification after kratom (mitragyna speciosa) dependence. European Addiction Research 16(4): 229-231, 2010. (11 refs.)

Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.

Meader N. A comparison of methadone, buprenorphine and alpha(2) adrenergic agonists for opioid detoxification: A mixed treatment comparison meta-analysis. Drug and Alcohol Dependence 108(1-2): 110-114, 2010. (38 refs.)

Objectives: The aim of this systematic review was to compare the efficacy of methadone, buprenorphine, clonidine and lofexidine for opioid detoxification. Mixed treatment comparison meta-analyses were used to synthesise the data as it is designed for data-sets where limitations in standard pairwise meta-analyses make comparisons difficult to interpret. Data sources: A systematic search was conducted using the following databases: CENTRAL, CINAHL, Embase, HMIC, Medline and PsycINFO. Review methods: RCTs that included opioid dependent participants over a mean age of 16 receiving opioid detoxification using buprenorphine, methadone, clonidine or lofexidine were included in the systematic review. Included studies were quality assessed and the completion of treatment data was extracted by the author and a research assistant independently. Mixed treatment comparison methods were used to synthesise the data. Results: There were 23 RCTs included in the systematic review (and 20 included in the meta-analysis) comprising a total of 2112 participants. Buprenorphine and methadone were ranked as the most effective methods of opioid detoxification followed by lofexidine and clonidine respectively. Conclusion: Buprenorpine and methadone appear to be the most effective detoxification treatments. While the analysis suggests buprenorphine is the most effective method of detoxification there is some uncertainty on whether it is more effective than methadone and requires further research to confirm this result.

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

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

Mullen L; Keenan E; Barry J; Long J; Mulholland D; Grogan L et al. Factors predicting completion in a cohort of opiate users entering a detoxification programme. Irish Journal of Medical Science 179(4): 569-573, 2010. (16 refs.)

To determine the outcome and factors influencing outcome among a cohort of drug users commencing detoxification from opiate use. National cohort study of randomly selected opiate users commencing methadone detoxification treatment in 1999, 2001 and 2003 (n = 327). One quarter 62 (25.6%) of opiate users had a successful detoxification within the 3-month study criteria. Receiving some inpatient treatment as part of detoxification programme resulted in completion by 56.3% drug users compared to outpatient only treatment (21%). The factors independently influencing detoxification are as follows: having some inpatient treatment AOR 5.9 (2.63-13.64) and never having injected AOR 2.25 (1.20-4.25). An additional 31 (9%) opiate users had a detoxification between 3 months and 1 year and 27 (8%) moved into methadone maintenance. This study finds that having some inpatient treatment increases the likelihood of a detoxification within 3 months. Offering a detoxification early in a drug using career pre-injecting drug use should be considered for suitable and motivated patients.

Ockert DM; Volpicelli JR; Baier AR; Coons EE; Fingesten A. A non-opioid procedure for outpatient opioid detoxification. Journal of Addiction Medicine 5(2): 110- 114, 2011. (21 refs.)

Objectives: (1) To describe a new protocol using nonopioid medications (clonidine, lorazepam, trazodone, and a stimulant) to successfully complete outpatient opioid detoxification, (2) to determine clinical and demographic characteristics of patients who successfully complete an outpatient opioid detoxification, and (3) to determine the safety and clinical utility of the use of this combination of medications in the treatment of opioid withdrawal. Methods: In a posthoc evaluation study in a New York State-licensed outpatient detoxification unit of a substance abuse treatment facility, 223 heroin-dependent adults presenting for treatment were provided outpatient opioid detoxification. In the course of the opioid detoxification protocol of the facility, patients received clonidine, lorazepam, trazodone, and either a stimulant (methylphenidate or modafinil) or no stimulant, in combination on a daily basis. At each daily visit, signs and symptoms were assessed, and medications and dosing instructions were given for the following 24 hours. On completion of the detoxification protocol, patients were induced with oral naltrexone. Results: Overall, 61.0% (136) of the patients in this study successfully completed the outpatient detoxification protocol and were induced with naltrexone. Pretreatment demographic variables that predicted successful treatment included full-time employment, family support, private medical insurance, and referral by an employee assistance program. About 77% of patients with good prognosis successfully completed outpatient detoxification treatment. The addition of a stimulant improved patient retention and reduced the incidence of hypotension. Conclusions: The outpatient detoxification of opioid-dependent patients without the use of opioids has traditionally led to such high drop out rates that most clinical programs do not even consider the option. This makes it difficult to induce patients with opioid antagonists such as oral naltrexone or sustained release naltrexone. We describe a protocol here that leads to excellent rates of successful detoxification. This nonopioid detoxification methodology permits induction of naltrexone without the delay experienced in opioid-based titrations, and it thus facilitates the use of opioid antagonists for sustained abstinence, enhanced aftercare treatment outcomes, and opioid-free recovery.

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

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

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

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

Safari F; Mottaghi K; Malek S; Salimi A. Effect of ultra-rapid opiate detoxification on withdrawal syndrome18. Journal of Addictive Diseases 29(4): 449-454, 2010. (18 refs.)

The aim of study was determine the effect of ultra-rapid opiate detoxification (UROD) on the presence or absence of withdrawal syndrome in a group of patients with opiate dependency. In this study, withdrawal syndrome of 173 patients with opiate addiction was evaluated before and after UROD using the Objective Opioid Withdrawal Scale. Hence, each patient was observed for 5 minutes before UROD and at different hours afterward to observe any withdrawal sign. The most prevalent withdrawal sign before UROD was anxiety. Restlessness was the most prevalent finding at 1, 3, and 6 hours. After 12 hours, yawning was reported as the most prevalent finding in 39 participants. Anxiety was reported as the most prevalent finding in 61 participants after 24 hours. Patients with opioid dependency who underwent UROD showed the highest rate of withdrawal symptoms at one hour after anesthesia. Most of these symptoms subsided after 24 hours. UROD can be applied for detoxification of patients with opioid dependency with safety.

Salehi M; Kheirabadi GR; Maracy MR; Ranjkesh M. Importance of gabapentin dose in treatment of opioid withdrawal. Journal of Clinical Psychopharmacology 31(5): 593-596, 2011. (24 refs.)

Aim: The aim of the study was to evaluate the efficacy of gabapentin (1600 mg/d) as an adjunctive to methadone-assisted detoxification in the treatment of opioid withdrawal symptoms. Design: This was a 3-week open-label study (as second phase) following a double-blind, placebo-controlled study with 900 mg/d of gabapentin (as first phase of this study). Setting: The study was conducted at a specialized outpatient clinic for the treatment of patients with addictive disorders. Participants: The study subjects were composed of 27 patients addicted to opiate who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for opioid dependency, randomly selected among outpatients referred to our clinic. Intervention: Subjects received adjunctive treatment with gabapentin (1600 mg/d) in addition to methadone-assisted detoxification for 3 weeks. Measurements: Subjective Opiate Withdrawal Scale (SOWS) with a total score of 0 to 64 was administered at 6 time points during the study. Findings: The total SOWS score was significantly decreased after the intervention. Compared to our previous trial, an almost significant difference was observed in total SOWS scores between groups treated with gabapentin 1600 and 900 mg/d at the end of the intervention period (P = 0.06). Gabapentin with a dose of 1600 mg/d was significantly superior to a dose of 900 mg/d in decreasing severity of coldness, diarrhea, dysphoria, yawing, and muscle tension. Conclusions: Add-on gabapentin with a dose of 1600 mg/d is effective in reducing some of the withdrawal symptoms in patients addicted to opiate undergoing methadone-assisted detoxification.

Shaw C. The effectiveness of an innovative model of community opiate detoxification provided on a supported one-to-one basis. Journal of Substance Use 15(5): 340-351, 2010. (30 refs.)

Aim: To evaluate the effectiveness of an innovative model of community opiate detoxification provided on a supported one-to-one basis. Method: Analysis of data collected from participants who entered the detoxification programme during the pilot phase (March 2008-January 2009) is presented. Following an initial pre-detoxification interview each participant was subsequently interviewed at the end of detoxification and 1-month post-detoxification. Face-to-face structured interviews were conducted at each stage, which included items relating to drug use, drug withdrawal, desires for drugs, anxiety, depression, and arousal; and qualitative questions relating to participant's opinions regarding the detoxification programme. Results: Seventeen participants were admitted (15 males, mean age 39.2). Eleven participants (64.7%) exited the detoxification unit drug free. Non-significant decreases in drug use were observed amongst participants who completed follow-up. There was a significant reduction in participant's severity of withdrawal symptoms, but no difference in desires for drugs, depression, anxiety, or arousal. Participants felt positive about their detoxification experience and that the one-to-one model had contributed to detoxification success. Conclusions: This paper highlights the potential of a one-to-one model of opiate detoxification as an alternative to either the well established, home-based detoxification or the inpatient model. This study demonstrates its viability, initial level of effectiveness and positive participant perceptions, highlighting the requirement for further exploration of novel approaches to drug treatment.

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

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

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

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

Specka M; Buchholz A; Kuhlmann T; Rist F; Scherbaum N. Prediction of the outcome of inpatient opiate detoxification treatment: Results from a multicenter study. European Addiction Research 17(4): 178-184, 2011. (25 refs.)

Background: Monocentric studies of inpatient opiate detoxification treatment show considerable variability regarding treatment success rates. This multicentric study investigates whether patient characteristics explain the different rates of regular discharge between treatment units. Methods: 1,017 opiate-dependent patients from 12 detoxification units with similar treatment programs, funding, staffing and equipment were analyzed. Patient data and outcomes were documented by treatment staff using a standard form. Results: Controlling for center, regular discharge (range: 14-49% between centers) was significantly associated with pre-existing plans for follow-up treatment, previous completed long-term residential and detoxification treatments, fewer unsuccessful detoxification treatments, higher age, later onset of opiate use, and longer duration of use. Controlling for patient characteristics, the center variable was significantly associated with outcome in a multiple logistic regression analysis. Conclusions: Regular discharge could best be predicted by patients' plans for follow-up treatment and previous treatment outcomes. Although treatment units had equivalent resources and regulations, and although patient effects were statistically controlled for, there were still considerable center effects. Setting factors as well as actual drop-out processes should be investigated more closely in the future.

Veilleux JC; Colvin PJ; Anderson J; York C; Heinz AJ. A review of opioid dependence treatment: Pharmacological and psychosocial interventions to treat opioid addiction. (review). Clinical Psychology Review 30(2): 155-166, 2010. (119 refs.)

Opioid dependence is a problem of national concern, especially with dramatically increased rates of abuse and dependence of prescription opioids. The current article provides an up-to-date review of the literature on opioid dependence treatment, with a focus on conclusions drawn by experts in the field (e.g., Cochrane reviews and meta-analyses) and methodologically rigorous studies (e.g., randomized controlled trials). We describe the major classes of drug treatments available, including opioid agonist (e.g., methadone, buprenorphine, LAAM), antagonist (e.g., naltrexone) and non-opioid pharmacotherapies (e.g., alpha2 adrenergic agonists). These treatments are discussed in the context of detoxification and long term treatment options such as abstinence-based and maintenance strategies. We review the state of the literature as to prevention of opioid overdose and discuss the widespread problem of comorbidity among opioid-dependent populations. We also focus prominently on evidence for inclusion of psychosocial approaches in treatment regimens, either as stand-alone or in conjunction with psychopharmacological options.