Dose-Response Effects of Methadone in the Treatment of Opioid Dependence Acupuncture for the Treatment of Opiate Addiction Methodological Issues in Evaluating Auricular Acupuncture Therapy for Problems Arising from the Use of Drugs and Alcohol Lapse and relapse following inpatient treatment of opiate dependence. Acupuncture heroin detoxification: a single-blind clinical trial. Auricular acupuncture for drug dependence: an open-label randomized investigation on clinical outcomes, health-related quality of life, and patient acceptability. Auricular acupuncture as an adjunct to opiate detoxification treatment: effects on withdrawal symptoms.
It is estimated that more than 500 000 people in the United States are dependent on opioids [ 1 , 2 ] . Methadone , a synthetic opioid first reported as a treatment agent for opioid dependence by Dole and Nysw and er in 1965 [ 3 ] , is the most widely used pharmacologic treatment for opioid dependence . The National Drug and Alcoholism Treatment Unit Survey ( NDATUS ) determined a point prevalence of 92 715 opioid abusers treated in 758 methadone treatment programs on 30 September 1989 [ 4 ] . When used in conjunction with counseling services , methadone treatment has been associated with reduced rates of criminal activity , illicit drug use , and needle sharing and with improved rates of employment [ 5 - 9 ] . With the recognition of intravenous drug use as a primary risk factor for infection with human immunodeficiency virus ( HIV ) , improved access to methadone treatment has been identified as an important means for reducing the risk of HIV infection [ 10 , 11 ] . Although methadone treatment is effective in decreasing opioid use , recent studies have reported considerable variability across clinics in rates of continued intravenous drug use during treatment [ 12 ] . One aspect of this problem is that intravenous use of cocaine has become a serious problem among  methadone treatment patients [ 13 - 16 ] . Few systematic studies have addressed the efficacy of  methadone treatment since the onset of the cocaine epidemic [ 17 ] . Such research could re-evaluate in a contemporary population sample methadone 's specific pharmacologic efficacy in decreasing opioid use [ 18 - 20 ] while providing new information about any potential effect of methadone treatment on concurrent cocaine use . The issue of appropriate methadone dosing levels is highly pertinent because low-dose treatment has been strongly associated with poor drug use outcomes in descriptive clinical studies [ 12 , 21 ] and because a substantial number of clinics continue to use low doses of methadone [ 22 ] . For example , a report prepared by the General Accounting Office ( GAO ) that summarized the dosing practice s of 24 methadone programs in eight states found that doses ranged widely ( from 21 to 68 mg ) and 29 % had a mean dose of less than 40 mg [ 23 ] . Thus , despite more than 25 years of clinical experience , optimal dosing levels of methadone remain controversial [ 24 , 25 ] . Previous studies of methadone dosing have either surveyed clinics for their dosing practice and related doses to clinic-wide outcomes or have r and omly assigned patients to a specific predetermined dose of methadone using clinical trial methods . Naturalistic survey studies [ 5 , 6 , 12 , 21 , 26 ] , although valuable for identifying associations between dose and outcome , are method ologically compromised by confounding factors that differ across the clinics surveyed . Previous early clinical trials of methadone dosing [ 27 - 29 ] are also method ologically compromised ( for example , being single-blinded ) or only tested higher doses of methadone [ 30 ] . Thus there is a need for well-controlled research on methadone dosing reflecting doses in common use and incorporating the changing patient population . In this controlled clinical trial we compared moderate and low methadone dosing to methadone-free treatment , providing data in a contemporary population sample of opioid addicts and examining the effect of methadone dose on cocaine as well as opioid use . Methods Participants were 247 persons who had consecutive admissions to a methadone research clinic from September 1988 through July 1990 . The mean age was 34 years , 70 % were male , and 50 % were black . Most were unmarried ( 84 % ) and unemployed ( 62 % ) . They had an average of 11 years of education , were generally legally free ( 72 % ) , and had a mean of two previous admissions for drug abuse treatment . Their primary drug of choice was intravenous heroin , and 47 % reported using cocaine in the 30 days before their application to treatment . Eligibility criteria for study participation were age between 18 and 50 years , history of intravenous opioid dependence ( including documentation of previous treatment for opioid dependence or legal involvement secondary to opioid use , a urine sample positive for opioids , and physical examination consistent with acute and chronic needle use ) , no chronic medical illnesses , absence of a major mental illness , a negative pregnancy test for women , and at least 3 months since the patient 's last treatment at the clinic . Applicants who failed to fulfill the study 's eligibility criteria were assisted in seeking an alternate treatment program . The study was approved by the institutional review board , and informed consent was obtained from each patient at the time of admission to the study . Study Procedures Applicants who fulfilled the eligibility criteria were admitted to a 6-month short-term methadone treatment program .  Participants were stratified as to race and sex and were assigned to one of three fixed-dose methadone schedules ( Figure 1 ) . Treatment group assignment , stabilization doses , and dosing schedules were double-blind for all patients and the clinic staff who had patient contact . All patients received a minimum of 35 days of active methadone during the first 5 weeks of treatment ; this was followed by a 15-week stabilization period at either 50 , 20 , or 0 mg of methadone . Thus , patients assigned to the 0-mg treatment group received 35-day methadone detoxification . During weeks 21 through 26 , the methadone dose was gradually tapered for those patients still receiving active medication because this was a short-term ( 182-day ) treatment episode . A sub sample of patients ( n = 44 ) assigned to the 0-mg treatment group received a more prolonged ( 8-week ) induction period , reaching 0 mg at the start of week 9 to compare the effects of a faster to a slower detoxification protocol . In this report data for patients in the alternate 0-mg treatment groups are collapsed . Figure 1 . Dosing schedule . Treatment Procedures Patients were assigned an individual counselor who set treatment goals and developed an individualized treatment plan . Patients were given weekly group therapy focusing on relapse prevention . On-site medical services were provided by a full-time internist and a part-time nurse practitioner . Take-home medication was provided only on legal holidays and for documented extenuating circumstances ( for example , funeral out of town for a death in the family ) . Patients who failed to attend the clinic for 3 consecutive days were discharged from treatment . Outcome Measures Treatment Retention and Compliance Treatment retention was calculated as the total number of days between the day of admission and the day of discharge , or the last day of the stable dosing period ( day 140 ) if the patient remained in treatment beyond the stable dosing period . Compliance with treatment was assessed through treatment attendance , the number of days medicated divided by days in treatment , and counseling contacts , which were based on the length ( minutes ) and number of contacts the patient had with either individual or group treatments . Urine Testing Patients provided a supervised urine sample for toxicology screening three times per week . Sample s were tested on-site using EMIT ( Syva Corporation , Palo Alto , California ) for the presence of opioids , cocaine , and benzodiazepines ; and cut-off calibration concentrations were set at 300 g/mL for each test ( morphine , benzoylecgonine , oxazepam ) . The specificity of the EMIT system ranges from 96 % to 100 % . One sample each week was r and omly selected to be sent to an outside laboratory for thin-layer chromatography analysis , which detects these same compounds and a wide variety of other less commonly abused substances . Data Analysis Retention to week 20 , days in treatment , percentage of days attended , and amount of counseling contact time were analyzed with a one-way analysis of variance with methadone dose as the grouping factor and the Tukey Honestly Significant Difference ( HSD ) test was used for post hoc analyses . Comparisons for which the critical difference value corresponding to P < 0.05 are reported as significant for this and all subsequently described analyses . Treatment survival curves were compared using the Lee-Desu statistic , with pairwise comparisons between each of the three treatment groups . The percentages of urine positive for opioids , cocaine , benzodiazepines , and any other drugs were calculated for each patient through the end of the stable dosing period . A one-factor analysis of variance with methadone dose as the grouping factor was used for each of these analyses . Results Table 1 shows the demographic features of the 247 patients enrolled in the study . The only difference across the three treatment groups on any variable was marital status ; 8 % of the patients in the 50-mg treatment group were married compared to 17 % in the 20-mg and 25 % in the 0-mg groups . Table 1 . Demographic Characteristics for Patients ( n = 247 ) Assigned to Different Methadone Doses * Treatment Retention and Compliance Orderly dose effects were seen for survival in treatment ( Figure 2 ) . Although the three treatment groups had similar rates of retention during the first 4 weeks of treatment , when all participants were receiving active methadone , retention rates diverged between weeks 4 and 8 and dose effects were seen from weeks 8 through 20 . In the survival analysis , there was an overall difference between the three curves ( P < 0.01 ) , and pairwise comparison between the 50-mg and 0-mg treatment groups differed significantly ( P < 0.01 ) ; the differences between the 50-mg and 20-mg , and 20-mg and 0-mg treatment groups approached significance ( P = 0.1 and P = 0.08 , respectively ) . At week 20 , the end of the stable dosing period , retention was 52.4 % for the 50-mg , 41.5 % for the 20-mg , and 21.0 % for the 0-mg groups ( 50 versus 0 and 20 versus 0 , P < 0.05 ; 50 versus 20 , P > 0.05 ) . Figure 2 . Retention in treatment . n The number of days retained in treatment was also dose related ( P < 0.01 ) ; Acupuncture is an accepted treatment worldwide for various clinical conditions , and the effects of acupuncture on opiate addiction have been investigated in many clinical trials . The present review systematic ally analyzed data from r and omized clinical trials published in Chinese and English since 1970 . We found that the majority agreed on the efficacy of acupuncture as a strategy for the treatment of opiate addiction . However , some of the methods in several included trials have been criticized for their poor quality . This review summarizes the quality of the study design , the types of acupuncture applied , the commonly selected acupoints or sites of the body , the effectiveness of the treatment , and the possible mechanism underlying the effectiveness of acupuncture  in these trials Auricular acupuncture is an accessible , non-confrontational therapy that appears to be effective when used in drug and alcohol treatment facilities , hospitals and prisons in the UK , Europe and the USA . Despite being popular , research evidence on its effectiveness is lacking , and as a result services are underfunded and risk being withdrawn . There are method ological problems in research ing auricular acupuncture . In these days of evidence -based medicine , most studies in this area are explanatory r and omised controlled trials , which is limited in capturing the complete benefits of the intervention . Furthermore , there is lack of consensus over definitions of the concept of ‘ addiction ’ and whether or not this should be perceived as a ‘ disease ’ that can be ‘ cured ’ by an intervention such as auricular acupuncture . Basic concepts such as these need to inform development of outcome measures , which should include retention of clients in treatment as an indicator of success . It is argued here that the best approach will integrate research on physical effects with research on subjective experience of those with drug and alcohol problems . The challenge is to design large scale , high quality , pragmatic r and omised controlled trials to assess the effectiveness of  auricular acupuncture over the longer term in setting s that mimic the delivery of treatment in practice and are informed by acupuncture 's own diagnostic traditions , using a combination of objective , quantitative methods and subjective , qualitative methods We conducted a prospect i ve follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification . We measured the rate of relapse following discharge , and sought to identify factors that were associated with early relapse ( i.e. , a return to daily opiate use ) . Follow-up interviews were conducted with 109 patients , of whom , 99 ( 91 % ) reported a relapse .  The initial relapse occurred within one week in 64 ( 59 % ) cases . Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age , greater heroin use prior to treatment , history of injecting , and a failure to enter aftercare . Unexpectedly , those who were in a relationship with an opiate user had significantly delayed relapse . Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse . In order to reduce relapse and the associated increased risk of fatal overdose , services providing residential opiate detoxification should prepare people for admission , strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome The increasing prevalence of HIV infection among injection drug users m and ates the development of innovative treatments . While extensive clinical experience suggests that acupuncture detoxification is both safe and acceptable to those in withdrawal , little research has been conducted to assess its efficacy as a treatment modality . In this first controlled study of acupuncture heroin detoxification , 100 addicted persons were r and omly assigned , in a single-blind design , to the st and ard auricular acupuncture treatment used for addiction or to a " sham " treatment that used points that were geographically close to the st and ard points . Attrition was high for both groups , but subjects assigned to the st and ard treatment attended the acupuncture  clinic more days and stayed in treatment longer than those assigned to the sham condition . Additionally , attendance varied inversely with self-reports of frequency of drug use , suggesting that those with lighter habits found the treatment modality more helpful . Limitations of the study are discussed CONTEXT Substance abuse has been prevalent in Malaysia for many years and currently represents one of the main concerns to its society . The limitations of conventional therapies have result ed in efforts to explore the potentia of complementary therapies in the management of drug addiction . The evidence for auricular acupuncture ( AA ) as a potential complementary therapy for drug addiction is still limited and inconclusive . OBJECTIVE The study intended ( 1 ) to compare the clinical outcomes of methadone maintenance treatment ( MMT ) alone and MMT plus AA ( MMT+AA ) with regard to the daily methadone dose , number of cigarettes smoked/wk , relapse rates , and withdrawal symptoms ; ( 2 ) to evaluate health-related quality of life ( HR QoL ) pre- and postintervention ; and ( 3 ) to determine participants ' acceptance of AA therapy . DESIGN The research team design ed this study to be prospect i ve , longitudinal , open-labeled , and r and omized , with one intervention group ( AA group ) and one control group . SETTING The setting s were three MMT centers in Terengganu , Malaysia : ( 1 ) the Methadone Maintenance Treatment ( MMT ) Center , Hospital Sultanah Nur Zahirah ; ( 2 ) the MMT Center , Marang Health Clinic ; and ( 3 ) the MMT Center , Seberang Takir Health Clinic . PARTICIPANTS Participants were individuals who were enrolled in the three MMT programs . INTERVENTION After r and omization , the intervention group received MMT+AA while the control group received MMT only . Participants in the AA group underwent concurrent AA sessions for 8 wk . OUTCOME MEASURES All outcomes were evaluated using question naires that the research team developed and WHOQOL-BREF . Data were analysed employing descriptive and nonparametric statistics ( SPSS v16 ) . RESULTS A total of 97 , eligible , male patients consented to participation ( MMT = 42 ; MMT+AA = 55 ; median age = 36.0 y ; Malay ethnicity = 97.9 % ) . After screening for dropouts , the data from only 69 participants were considered for postintervention analysis ( MMT = 40 ; MMT+AA = 29 ) . At preintervention , participants differed significantly by HR QoL profile and the frequency of withdrawal symptoms ( better for MMT participants ) . Postintervention , all groups reported significantly reduced numbers of cigarettes smoked and a reduced methadone dose ( P < .05 ) , whereas no significant difference was detected for other parameters . No difference for relapse rate was detected between the groups . On separate group analysis , only the number of cigarettes was significantly lower for MMT+AA participants , whereas apart from methadone dose , all other parameters had significantly improved over time in the MMT+AA cohort . The additional AA therapy also demonstrated favorable acceptance and tolerable side effects . CONCLUSION Findings implied that AA could be beneficial as an adjunct to MMT in managing addiction , but the effectiveness of AA still requires further extensive investigation 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 r and omized , 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 question naire . 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 st and ard 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
BACKGROUND AND OBJECTIVES Opioid use disorder ( OUD ) is a chronic disease with significant personal , societal , and public health consequences .
Even for the minority who receive the most effective evidence -based treatments , morbidity , and mortality remain significant .
These facts , along with the recovery movement calling for individualized , holistic , culturally sensitive care , have led to the exploration of adjunctive interventions including acupuncture .
Despite hundreds of international trials , however , there is a lack of consensus regarding its efficacy in OUD due in large part to method ological issues of trials to date .
In response to these issues , the National Acupuncture Detoxification Association ( NADA ) developed an operationalized manual auricular acupuncture protocol that has since become the most widely used in the US .
This systematic review is the first to focus explicitly on r and omized trials utilizing the NADA protocol as a complementary intervention to address OUD .