Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function

Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.     

EEG findings in heroin addicts during induction and maintenance on methadone.

This study investigated changes in the EEG of addicts initially on heroin as they progressed through the induction and maintenance phases of a methadone program. Spectral analysis of bipolar recordings revealed significant consistent differences only in the eyes-closed resting state. Patients under the influence of heroin showed large sharp peaks at 9-10 c/sec, particularly in the parieto-occipital recording. Methadone induction led either to marked reduction of this peak and widening of alpha band activity or to an increase in frequency of the alpha peak to 12 c/sec. After several months of methadone the alpha peak was still absent unless heroin abuse was present, a theta peak was present in three of four patients, and the alpha bandwidth remained broad. Changes in the theta band were more difficult to interpret.     

Discrimination of opiate dependence from opiate abstinence and methadone maintenance by use of the Derogatis scale

A sample of opiate addicts from the Basle area followed over six years (1979-1985) was in 1985 investigated concerning psychopathological features. Using the Derogatis scale significant differences between opiate abstinence and opiate dependence could be demonstrated. People still using opiates described themselves as being more obsessive, insecure, depressed, aggressive and anxious than people who had become abstinent from opiates. Patients in methadone maintenance were located in between. There were in addition significant differences between people living outside an institution and people being treated in therapeutic or penal institutions, but no differences between people from each kind of institution.     

Imipramine treatment of methadone maintenance patients with affective disorder and illicit drug use

Of 17 consecutive patients receiving methadone maintenance treatment who had primary or chronic depression, nine (53%) improved in both mood and drug abuse after imipramine treatment. This finding suggests a potential for helping such dual-diagnosis patients reduce drug abuse and associated risk for HIV. Further controlled trials are warranted.     

Increasing leptin precedes craving and relapse during pharmacological abstinence maintenance treatment of alcoholism

The appetite regulating peptide leptin has recently been associated with craving for alcohol and lifetime ethanol intake. However, effects of anti-craving drugs on leptin have not been studied until now. The objective of our study was to test the hypothesis whether leptin plasma concentration in abstinent alcohol addicts during treatment with naltrexone vs. acamprosate is associated with abstinence duration and craving for alcohol. Leptin plasma concentration was measured in 160 recently detoxified alcohol addicts during a double-blind, placebo-controlled relapse prevention trial with naltrexone vs. acamprosate vs. naltrexone plus acamprosate. During placebo treatment, increasing leptin plasma concentration was observed, whereas during combined treatment with naltrexone and acamprosate, leptin decreased significantly. The change from baseline of leptin plasma levels after weeks 4, 8 and 12 was inversely correlated with duration of abstinence and, after 4 weeks, positively correlated with self-rated craving. In summary, the study presents first evidence for an association of increasing leptin plasma concentrations with relapse to renewed alcohol intake in detoxified alcoholics. Moreover, there are hints for an interaction between pharmacological anti-craving treatment, plasma concentration of leptin, and abstinence duration.     

A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence

BACKGROUND: This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT). METHODS: Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission. RESULTS: Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data. CONCLUSIONS: Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group.     

Heroin craving and its correlations with clinical outcome indicators in people with heroin dependence receiving methadone maintenance treatment

BackgroundCraving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5. However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire–Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT).MethodSelf-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected.ResultsThe results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use.ConclusionsThis study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.     

Mortality in heroin addiction: impact of methadone treatment

The mortality within a cohort of 115 street heroin addicts was studied for 5-8 years using the Kaplan-Meier survival estimate technique. This differed markedly from the relatively low mortality of 166 comparable heroin addicts given methadone maintenance treatment (MT). The street addicts' mortality rate was 63 times that expected, compared with official statistics for a group of this age and sex distribution. When 53 patients in MT were involuntarily expelled from treatment, due to violation of programme rules, they returned to the high mortality of street addicts (55 times that expected). A group of 34 rehabilitated patients who left MT with medical consent retained the low mortality of MT patients (their mortality rate was 4 times that expected). Despite this great improvement in survival, even patients in MT showed a moderately elevated mortality (8 times that expected), mainly due to diseases acquired before entering the treatment programme. It is concluded that MT exerts a major improvement in the survival of heroin addicts.     

多巴胺2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状相关性研究

目的研究昆明市美沙酮维持治疗A门诊接受美沙酮维持治疗的汉族海洛因依赖者多巴胺D2受体基因TaqIA多态性与接受美沙酮维持治疗海洛因依赖患者心理症状的相关性,探讨影响病人治疗效果的遗传因素。方法对81例接受美沙酮维持治疗的海洛因依赖者实施SCL-90测试,应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术,检测多巴胺D2受体基因TaqIA基因多态,比较不同基因型与SCL-90各因子的关系。结果 A1＋组（A1/A1,A1/A2）与A1-组（A2/A2）SCL-90各因子分无显著性差异。结论D2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状可能不存在相关性。     

Safety of injectable opioid maintenance treatment for heroin dependence.

BACKGROUND: There is a growing debate about injectable opioid treatment programs in many Western countries. This is the first placebo-controlled study of the safety of injectable opioids in a controlled treatment setting. METHODS: Twenty-five opioid-dependent patients on intravenous (IV) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo. Acute drug effects were recorded, focusing on electrocardiography, respiratory movements, arterial blood oxygen saturation, and electroencephalography (EEG). RESULTS: After heroin injection, marked respiratory depression progressing to a Cheyne-Stokes pattern occurred. Peripheral arterial blood oxygenation decreased to 78.9 +/- 8.7% (mean +/- SD) ranging from 52%-90%. During hypoxia, 7 of the 16 subjects experienced intermittent and somewhat severe bradycardia. Five subjects exhibited paroxysmal EEG patterns. After methadone injection, respiratory depression was less pronounced than after heroin injection. No relevant bradycardia was noted. CONCLUSIONS: Opioid doses commonly prescribed in IV opioid treatment induce marked respiratory and circulatory depression, as well as occasionally irregular paroxysmal EEG activity. Further studies are needed to optimize the clinical practice of IV opioid treatment to prevent serious complications. Moreover, the extent of the observed effects raises questions about the appropriateness of IV opioid treatment in the present form.     

A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial

OBJECTIVE: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. METHOD: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. RESULTS: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. CONCLUSIONS: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.     

The relationship between substance use and posttraumatic stress disorder in a methadone maintenance treatment program

Introduction and Aims

Posttraumatic stress disorder (PTSD) is frequently linked with substance abuse. The self-medication hypothesis suggests that some people may use illicit substances in an attempt to self-treat psychiatric symptoms. This study explores the relationship between substance abuse and PTSD symptom clusters in a methadone maintenance population.

Design and Methods

Clients of a methadone maintenance program at a public Drug and Alcohol Service were invited to complete the PTSD Checklist–Civilian Version, a screening tool for PTSD. Information about their history of substance use was also collected.

Results

Eighty clients (43 female, 37 male), aged 35 ± 8.0 years (mean ± SD), participated in the study, of which 52.7% screened positive for PTSD. Severity of marijuana use was significantly associated with a number of reexperiencing and hyperarousal symptoms and with overall severity of PTSD symptoms. Opiate, amphetamine, and benzodiazepine use did not appear to be related to PTSD symptoms.

Discussion and Conclusions

In this sample, marijuana may be used to self-treat certain PTSD symptoms, supporting the self-medication hypothesis. Further research is required to confirm the association between a diagnosis of PTSD and substance use. Given the high prevalence of PTSD in the substance-using population, routine PTSD screening in the substance abuse treatment setting may be justified.