Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)     

A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence

BACKGROUND: Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance. METHODS: Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period. RESULTS: Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted. CONCLUSIONS: Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.     

Buprenorphine treatment of opioid dependence: A review.

Buprenorphine, a partial mu-agonist opioid, is a promising pharmacotherapy for the treatment of opioid dependence. One hundred and eight papers are organized according to 3 components essential to buprenorphine's use as a pharmacotherapy for opioid dependence: inducting patients onto buprenorphine, maintaining patients on buprenorphine, and discontinuing patients from buprenorphine treatment. The research suggests that inducting patients onto buprenorphine should lead to limited discomfort if appropriate procedures are followed. As a maintenance treatment, buprenorphine is as efficacious as methadone, blocks the effects of exogenously administered opioids, promotes treatment compliance, and, importantly, can support an alternate day dosing regimen by doubling the daily dose. Discontinuing buprenorphine treatment appears to result in a mild-to-moderate opioid withdrawal syndrome that is less severe than that observed with full-efficacy agonists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of outcome in LAAM, buprenorphine, and methadone treatment for opioid dependence.

This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and cocaine use were assessed. We believe this study to be the first to demonstrate that predictors of treatment success appear to be largely similar in LAAM, buprenorphine, and methadone treatment for opioid dependence. We did not find any factors that would strongly guide selection of one medication over others. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute opioid dependence in the cardiovascular system of the spinal rat

A cluster of infections caused by Enterobacter cloacae was observed among preterm neonates in a neonatal intensive care unit (NICU) of a pediatric hospital in Osnabrück, Germany. The presence of similar antimicrobial susceptibility patterns among the bacterial isolates prompted an investigation to determine whether a limited spread of a single strain existed. All 12 E. cloacae isolates from the NICU and 50 nonrelated strains were fingerprinted by small-fragment restriction endonuclease analysis (SF-REA) of EcoRI DNA digests. Selected isolates were further characterized by pulsed-field gel electrophoresis (PFGE) of NotI- or XbaI-generated genomic restriction fragments. Epidemiologically unrelated strains were clearly discriminated by both methods. Results achieved by SF-REA and PFGE revealed that of the 12 isolates from the NICU, 11 belonged to the same genotypic cluster. Since all reagents and equipment for both techniques are commercially available, DNA fingerprinting by SF-REA or PFGE is proposed as a useful tool in the microbiology laboratory for investigating the epidemiological relatedness of E. cloacae strains of clinical and environmental origin.     

Contingency management to enhance naltrexone treatment of opioid dependence: A randomized clinical trial of reinforcement magnitude.

Fifty-five detoxified opioid-dependent individuals were randomly assigned to 1 of 3 treatments delivered over 12 weeks: standard naltrexone maintenance, standard naltrexone plus low-value contingency management (CM), or standard naltrexone plus high-value CM. Results suggest that (a) assignment to either CM condition was associated with significant reductions in opioid use over time compared with standard naltrexone treatment; (b) contrasts of high- versus low-value reinforcement magnitude were not significant, suggesting no relative benefit of higher over lower value incentives in this population; (c) participants assigned to either CM group reported significant reductions in readiness to change compared with participants assigned to standard naltrexone treatment. These findings suggest that targeted behavioral therapies can play a substantial role in broadening the utility of available pharmacotherapies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions

Studies of direct excitatory effects elicited by opioid agonists on various types of neurone have been confirmed and expanded in numerous laboratories following the initial findings reviewed previously by Stanley Crain and Ke-Fei Shen. However, the critical role of the endogenous glycolipid GM1 ganglioside in regulating Gs-coupled, excitatory opioid receptor functions has not been addressed in any of the recent reviews of opioid stimulatory mechanisms. This article by Stanley Crain and Ke-Fei Shen focuses on crucial evidence that the concentration of GM1 in neurones might, indeed, play a significant role in the modulation of opioid receptor-mediated analgesia, tolerance and dependence.     

Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence

The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. naloxone. In butorphanol-dependent rats, the spinal kappa-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal delta- and mu-opioid receptors did. In contrast, the spinal mu-opioid receptor became more sensitive than the delta-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.     

Role of NMDA receptors in pentobarbital tolerance/dependence

Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300 micrograms/10 microliters/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK-801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10 microliters/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK-801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.     

The significance of a coexisting opioid use disorder in cocaine dependence: an empirical study

This study was undertaken to compare cocaine-dependent patients with and without an opioid use disorder, in an effort to identify important clinical similarities and differences between the two groups. Ninety patients hospitalized for cocaine dependence were divided according to whether or not they had a coexisting opioid use disorder; 32 patients (35.6%) had an opioid diagnosis and 58 (64.4%) did not. The groups were compared on substance use histories, psychopathology, severity of drug-related problems, and 3-months cocaine use outcome. Patients with an opioid diagnosis had more current major depression, antisocial personality disorder, and other substance use disorders. They also had higher medical and drug scores on the Addiction Severity Index, and longer cocaine use histories. Nonetheless, 3-month cocaine use outcome was similar for both groups. Interestingly, patients with an opioid diagnosis engaged in more treatment during the follow-up period. Cocaine-dependent patients with a coexisting opioid use disorder may thus constitute a subgroup with worse prognostic characteristics, for whom differential treatments may improve outcome.     

Role of central opioid receptor subtypes in morphine-induced alterations in peripheral lymphocyte activity

The implementation of the new global health policy "Health for All in the 21st Century" will be guided by global targets. Specific indicators will be developed to assess progress at all levels. This article outlines how these targets are directly related to the policy, indicating that the HFA targets are both inspirational and achievable. All 10 global targets will be discussed separately, exploring their epidemiological background and high-lighting the potential for the development of indicators.     

Acupuncture treatment of drug dependence in Pakistan

Wen's technique of electro-acupuncture was used successfully for treatment of withdrawal symptoms of 19 drug abusers. The drug common to all was opium (eating as well as smoking). Other drugs were amphetamine, methaqualone (mandrax) and barbiturates by mouth and cannabis (charas) smoking. The sample of the study is too small to draw statistical conclusions, but it is worth stating that all the cases showed a definite response to electro-acupuncture and that their withdrawal symptoms, especially those of opium, were controlled within 30 minutes of the application. The need for subsequent treatment varied, but all patients were symptom free and chemical free on the 6th-8th day of treatment. Thus, the period of active treatment was much shorter than that with codeine substitution therapy. It appears obvious that electro-acupuncture is an effective, simple and more economical method for the detoxification of opiate dependents.     

Ritanserin in the treatment of cocaine dependence

BACKGROUND: There have been numerous studies that have shown that offspring of depressed parents are at a high risk for major depressive disorder (MDD) and impairment. None have followed up the offspring into adulthood to obtain more precise estimates of risk. METHOD: One hundred eighty-two offspring from 91 families, in which 1 or more parents had MDD (high risk) or in which neither parent was depressed (low risk), were blindly reassessed in the third follow-up, using a structured diagnostic instrument 10 years after their initial identification. RESULTS: Compared with the offspring for whom neither parent was depressed, the offspring of depressed parents had increased rates of MDD, particularly before puberty, and phobias (both at approximately a 3-fold risk), panic disorder, alcohol dependence (at a 5-fold risk), and greater social impairment. The peak age at onset for MDD in both high- and low-risk offspring ranged from 15 to 20 years. The peak age at onset for anxiety disorder was considerably earlier, especially in female offspring in the high-risk group. The onset of alcohol dependence in the offspring in the high-risk group peaked in adolescence and then after the age of 25 years. The depressed offspring of depressed parents, compared with nondepressed parents, had more serious and impairing depressions during the follow-up period but were less likely to go for treatment. CONCLUSIONS: The offspring of depressed parents are a high-risk group for onset of anxiety disorder and MDD in childhood, MDD in adolescence, and alcohol dependence in adolescence and early adulthood. The findings support the potential value of early detection in the offspring of depressed parents.     

Problems with maintenance therapy in opiate dependence and the clinical importance of methadone]

The author presents a review of experience with substitution treatment in opiate dependence. Methadone treatment is most frequently used. An individual daily dose and long-term substitution are desirable for stabilization and motivation of patients included in the methadone programme. Interaction of methadone with some drugs affects the methadone metabolism and calls for a change of the methadone dose and must not be omitted. In addition to methadone there are also other types of pharmacotherapy of opiate dependence (acetylmethadol, buprenorphine). In the Czech Republic in 1997 in the General Faculty Hospital Prague the methadone programme was started. The importance of methadone substitution treatment is beyond doubt and involves improvement of the psychosocial and health status of addicts, gives an opportunity of resocialization and reintegration into society.     

Naltrexone and alcohol dependence. Role of subject compliance

BACKGROUND: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance. METHODS: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n = 48) or matching placebo (n = 49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week). RESULTS: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication. CONCLUSIONS: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance.