Does maintenance treatment reduce the mortality rate of opioid addicts?

Reduction of mortality is a basic goal of methadone maintenance treatment (MMT) for opioid addicts. During the last years, however, there have been reports about drug related deaths of MMT patients and of untreated drug addicts who had consumed illegally purchased methadone. To evaluate the supposed beneficial effect of MMT on mortality, data from a multicentre trial in the German state of North Rhine-Westphalia were analysed. 244 patients with long histories of opioid addiction and previous failures in at least two abstinence oriented treatments were observed for at least four years and up to eight years after admission to MMT. With 32 deaths out of 244 participants, the mortality rate for the whole sample was 2.5 % p.a. This rate is not remarkably different from estimations for opioid addicts in general. However, addicts in continuous maintenance treatment had a mortality rate of only 1.6 % p.a., in contrast to a rate of 8.1 % p.a. for addicts who had left treatment. These results are supported by other long-term studies with large patient samples. Therefore it is concluded that methadone maintenance treatment is a measure to reduce the mortality in opioid addicts. Attainment of this goal is threatened, however, by deviations from safety standards, especially if take-home privileges are granted too widely.     

Supervised daily consumption, contingent take-home incentive and non-contingent take-home in methadone maintenance

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.     

Review of deaths related to analgesic- and cough suppressant-opioids; England and Wales 1996-2002

OBJECTIVE: The data on England and Wales voluntarily supplied by Coroners to the National Programme on Substance Abuse Deaths for the August 1996-December 2002 time frame were analyzed. METHODS: All cases in which at least one analgesic- and cough suppressant-opioid other than heroin/morphine, methadone or buprenorphine was identified were extracted from the database. We hypothesized that: a) populations of addicts and non-addicts presented differences in patterns of drugs involved; and b) within the population of addicts and non-addicts, intentional and non-intentional deaths presented different patterns of substance consumption. RESULTS: A total of 2024 deaths related to selected opioids, either alone or in combination, were included in the analysis. Typically, non-addicts were older than 45 and died as a result of intentional poisoning whilst majority of addicts were young, males and victims of accidental deaths. In about 93% of cases the selected opioids were reported in combination with another substance. Most frequently identified narcotics were propoxyphene, codeine and dihydrocodeine. Co-proxamol, Co-codamol and Co-dydramol were typically prescribed for non-addicts, whilst dihydrocodeine was mostly given to addicts. In non-addicts, alcohol was mostly represented in accidental deaths and antidepressants were typically represented in intentional deaths. Conversely, illicit drugs and hypnotics/sedatives were typically reported in addicts' accidental deaths. CONCLUSIONS: The present report constitutes the largest available collection of analgesic- and cough suppressant-opioid mortality data in the UK. Users should be educated about risks associated with polydrug misuse.     

Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: preliminary results of an open randomized study

An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day.As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use.The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear.The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.     

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.     

Fatal poisoning in methadone and buprenorphine treated patients -- are there differences?

BACKGROUND: Some recent studies have suggested a lower risk of fatal intoxications in drug-dependent patients under buprenorphine compared to methadone treatment. METHODS: Epidemiological reference data for the Munich region suggest that in 2003 approximately 10 % of all substitution patients were treated with buprenorphine, and 87 % with methadone. We studied the proportion of patients under methadone and buprenorphine substitution among drug-related deaths. Data from forensic post-mortem and toxicological analysis were analyzed. RESULTS: Data indicate that in 96 (35 %) of all 272 so-called drug deaths, methadone was involved compared to a single case of buprenorphine, possibly indicating a relatively better risk profile of buprenorphine. DISCUSSION: More prospective studies are necessary to assess the risk of fatal intoxications under different substitution regimens.     

Relationship of depression to clonidine detoxification of opiate addicts

Moderate levels of self-rated depression were related to failure during outpatient detoxification from methadone maintenance in 44 ex-addicts. Failure among those ex-addicts with depression was just as likely using either clonidine or the slow tapering of methadone over 1 month. The Beck Depression score correctly predicted 80% of the failures. Demographic factors and psychosocial stressors, as assessed by the Addiction Severity Index, were not significantly associated with failure or depression. These findings support the general conclusion about opiate addicts that depression is a relatively strong predictor of treatment failure and that for even moderately depressed addicts inpatient detoxification or postponement of outpatient detoxification should be considered.     

Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone

Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group.     

长沙市芙蓉区美沙酮门诊海洛因依赖人群HIV、HCV和梅毒感染状况调查

目的 了解长沙市芙蓉区美沙酮门诊海洛因依赖人群HIV、HCV和梅毒感染情况及其危险因素.方法 对参加维持治疗的323名海洛因依赖者进行HIV、HCV梅毒血清学检测和问卷调查.结果 71％成瘾者采用静脉吸毒,6.9％的静脉吸毒者共用注射器.HIV抗体阳性率0.3％ (1/323) HCV抗体阳性率61％ (198/32...     

Urine screening practices in methadone maintenance clinics. A survey of how the results are used

The urinalysis practices of 324 methadone maintenance clinics were surveyed using a brief self-report questionnaire. Results indicate that there is wide variability in collection practices and clinic responses to positive findings. Virtually all clinics provide counseling and revocation of take-home methadone doses as a response to positive urinalysis results. However, increase in urine screening frequency, methadone dose adjustments, contingency contracting, group therapy, and eventual discharge are interventions also used. The implementation of different interventions varied as a function of clinic size, city size, region of the country, and program funding source.     

Innovations in agonist maintenance treatment of opioid-dependent patients

PURPOSE OF REVIEW: To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. RECENT FINDINGS: The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts. SUMMARY: Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.     

Buprenorphine responders: a diagnostic subgroup of heroin addicts?

1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets.     

Pathological gamblers are neither impulsive nor sensation-seekers

Ten pathological gamblers, ten alcoholics, ten heroin addicts and twenty five non-patients were compared using Zuckerman's Sensation Seeking Scale (SSS) and Barratt's Impulsivity Scale (BIS). The pathological gamblers did not differ from the non-patient group on either measure. Drug addicts scored significantly higher and alcoholics significantly lower than the pathological gamblers and the non-patient group on the SSS, while drug addicts scored significantly higher than the other groups on the BIS. The difficulties in defining impulsivity are discussed. It is suggested that the classification of pathological gambling as a disorder of impulse control should be reconsidered.     

Vergleichsuntersuchung von Buprenorphin und Methadon im Rahmen der Erhaltungstherapie Opiatkranker

The efficacy of buprenorphine in opioid dependent patients (n = 20) was compared to methadone maintained subjects (n = 20) in a randomized comparison trial. Sublingual application of buprenorphine as an alternative synthetical opioid is being compared to methadone during a 24 week study period. A trend (p = 0.06) could be found in the retention rate of investigated patients being maintained on a mean dosage of 63 mg oral applicable methadone (racemat of L- and D-methadone) in comparison to the group on a mean dosage of 7.3 mg buprenorphine (sublingual tablets). The dropout-rate of 11 subjects at the end of the study in the buprenorphine group was higher when compared to the dropout-rate of 5 in the methadone group. There was no significant difference between the two groups over the treatment period in respect to additional consumption of opiates, benzodiazepines and cocaine as evaluated through urine toxicology. The result in regard to compliance over the study period demonstrates that methadone appears to be the more successful oral opioid (p = 0.04). Nevertheless, efficacy of buprenorphine in maintenance could be demonstrated in the remaining subjects, and further studies with higher daily doses and a higher number of subjects have to be performed.     

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.     

Psychoactive Substance Use Among Methadone Maintenance Therapy Clients in China

A proportion of methadone maintenance therapy (MMT) clients in China shifted their substance use habit from opiate to psychoactive substances. The objective of this study was to examine the pattern and associated factors of psychoactive substance use among MMT clients. The study was conducted among 2448 clients from 68 MMT clinics of China. The type and frequency of psychoactive substance use were self-reported. About 38.1% (N = 933) of the participants reported psychoactive substance use in their lifetime, and 6.5% (N = 158) in the previous 30 days. The most commonly used psychoactive substances were sedative/hypnotic/antidiarrheal agent and amphetamine. Psychoactive substance use in the past 30 days was correlated with younger age, recent heroin use, having psychoactive substance-using friend(s), and depressive symptoms. The finding suggested that urinalysis of psychoactive substances should be routinely administered in the MMT clinics. Young clients, concurrent heroin users, and clients with depressive symptoms deserve more screening and intervention efforts.     

An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects

Background

The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months.

Methods

Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period.

Results

No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology.

Conclusions

Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.     

Methadone maintenance as a therapeutic approach in the treatment of opiate dependent patients

Treatment of opiate addicts is still difficult, and often has only limited success. Methadone therapy offers an alternative, in particular for patients who have repeatedly attempted conventional treatment without success. According to experience in Switzerland, about two-thirds of these patients become medically stable and socially rehabilitated during methadone therapy, or even drug-free in the long term following therapy. The therapy does not consist solely in a daily dose of methadone, but also involves intensive psychosocial care. In Germany, methadone therapy has been under discussion for more than 20 years. In this discussion doubts have been expressed about the criteria used to assess the indications for and the degree of success attained with methadone therapy. In addition, ethical arguments question whether social rehabilitation should be a primary goal of therapy. In order to objectify the discussion, methadone therapy is now being tested in Germany. A social consensus must be sought on goals and strategies in the treatment of opiate addicts.     

Buprenorphine does not aggravate ischemic neuronal injury in experimental focal cerebral ischemia

Buprenorphine has been increasingly used as maintenance therapy in opioid dependence as an alternative to methadone and other pharmacological therapies. However, available data suggest increased risk of cerebrovascular events in opioid-dependent patients. Therefore, an opioid that provides safety with regard to neurological function should be considered by opioid-dependent patients. The evidence for the in vitro neurotoxic effects of buprenorphine is rapidly increasing. In order to clarify whether buprenorphine is also neurotoxic under the condition of cerebral ischemia in vivo, we applied an acute dose of buprenorphine in a transient model of focal cerebral ischemia in rats. Our study provides preclinical evidence for the usage of buprenorphine during the postoperative period following ischemic events as well as for the maintenance therapy of opioid-dependent patients wherein the risk of cerebrovascular events is increased.     

Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.