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)     

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)     

Role of maintenance treatment in opioid dependence

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.     

A pilot study comparing severely and persistently mentally ill opiate-addicted patients in dual-diagnosis treatment with patients in methadone maintenance

Retroviral vector gene transfer strategies are currently being developed to treat a variety of hematopoietic disorders. To date, genetic modification of human pluripotent hematopoietic stem cells has been inefficient. In the present study we developed reagents and procedures for rapidly screening retroviral vector gene transfer conditions using a multiparameter fluorescence-activated cell sorting (FACS) assay. To identify transduced cells using FACS analysis, we developed a retroviral vector, termed MN, which stably expressed high levels of a truncated version of the low-affinity nerve growth factor receptor (LNGFR). In addition, procedures were developed for enriching CD34+ cells from cryopreserved umbilical cord blood. These cells were transduced with MN and evaluated using multiparameter FACS analysis for expression of CD34, CD38, and LNGFR. Stem cell maintenance was determined by measuring the CD34hi and CD34hiCD38lo/- cells remaining after ex vivo gene transfer. Gene transfer into these cells was measured by evaluating cells expressing high levels of LNGFR. Initial studies with this assay and with in vitro functional assays indicated that retroviral gene transfer following pre-incubation with a variety of cytokines in serum containing conditions resulted in 1) poor maintenance of hematopoietic stem cells and 2) gene transfer predominantly in relatively mature cells. When gene transfer in serum-free conditions was performed, some improvement was observed in the maintenance of cells retaining primitive immunophenotypes with no reduction in the gene transfer efficiency. The MN vector and multiparameter FACS analysis will be useful in efficiently screening ongoing efforts designed to improve stem cell gene transfer.     

A controlled trial of cue exposure treatment in alcohol dependence.

The clinical effectiveness of cue exposure (CE) treatment in alcohol dependence was evaluated in a controlled trial. 35 men who were detoxified and severely alcohol dependent received either CE or relaxation control (RC) treatment. CE Ss had 400 min exposure to the sight and smell of preferred drinks over 10 days in a laboratory setting. RC Ss spent identical time in the laboratory but had relaxation therapy and only 20 min exposure to alcohol cues. During 6-mo follow-up, personal interview was achieved with 91% of Ss. CE Ss had a more favorable outcome than the RC Ss in terms of latency (length of time) to relapse of heavy drinking (p?     

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.     

A prospective randomized controlled trial comparing suprapubic with urethral catheterization in rectal surgery

BACKGROUND: Bladder drainage is necessary for several days following rectal surgery. Urethral catheterization has long been known to be associated with significant morbidity. Therefore a prospective randomized trial was performed to determine if this morbidity could be decreased by suprapubic catheterization. METHODS: One hundred and thirty-seven patients undergoing rectal surgery were prospectively randomized to either suprapubic or urethral catheterization. RESULTS: After exclusions, 108 patients were analysed. Of the 49 patients with suprapubic catheters there was 14% morbidity, and of the 59 patients with urethral catheters there was 32% morbidity. Significant bacteriuria was halved with suprapubic catheterization. Patient acceptability of suprapubic catheterization was high, and there was no increased morbidity in any of the areas studied. CONCLUSIONS: This study suggests that suprapubic catheterization has advantages over urethral catheterization with decreased bacteriuria, and greater patient acceptability. However, the significance of decreased bacteriuria is not clear and therefore we can only say suprapubic catheter drainage is comparable to urethral catheter drainage.     

Love and hate in methadone maintenance

Different peptides of natural origin were studied for their stimulant activity on the stomach of the anaesthetized rat. The group of the tachykinins (substance P and its analogues) showed a noticeable spasmogenic activity on the whole stomach from the fundus to the pylorus. Threshold doses ranged between 0.1 and 5 microgram/kg by i.v. route and the order of potency was: eledoisin greater than phyllomedusin greater than physalaemin greater than uperolein greater than substance P. A good correlation between the dose and the duration of the spasmogenic effect was always observed and tachyphylaxis never occurred. Experiments carried out with different kinds of inhibitors suggested that tachykinins act directly on the smooth muscle of the stomach. Taking into account also results obtained in other experimental conditions it was possible to state that the N-terminal part of the molecule of these peptides has a certain importance in determining the degree of their potency in the different tests. The peptide motilin, which does not belong to the family from a chemical point of view, was scarcely active, if at all, in modifying the motility of the rat stomach.     

Naloxone-induced withdrawal in patients with buprenorphine dependence

Naloxone-induced withdrawal was studied in seven patients currently dependent only on injecting buprenorphine, within 3 to 6 hours of their last dose. Withdrawal severity began to rise from 5 minutes and reached a peak at 60 minutes after 1.2 mg naloxone given intravenously. The mean withdrawal severity score was significantly higher at 30, 60 and 90 minutes compared to the baseline. The most frequent withdrawal signs and symptoms were mydriasis, systolic hypertension, tachypnoea, muscle pains, yawning, anxiety, restlessness and craving.     

Randomized controlled trial comparing same-day discharge with hospital stay following haemorrhoidectomy

Neurological complications of 5-fluorouracil (5-FU) chemotherapy are uncommon events. The two patients presented demonstrate two manifestations of 5-FU neurotoxicity, namely a cerebellar syndrome in association with global motor weakness and bulbar palsy, and a bilateral third cranial (oculomotor) nerve palsy. Both highlight the rapid onset and severity of these unusual side effects but also emphasize that, unlike paraneoplastic syndromes or central nervous system involvement by tumour, complete spontaneous recovery is a potential outcome.     

A randomized controlled trial comparing two vocational models for persons with severe mental illness.

The authors compared 2 approaches to vocational rehabilitation for individuals with severe mental illness: the individual placement and support (IPS) model of supported employment and the diversified placement approach (DPA), which emphasizes work readiness and offers a range of vocational options, including agency-run businesses and agency-contracted placements with community employers. In all, 187 unemployed participants with severe mental illness were randomly assigned to IPS or DPA. Over 2 years, IPS had significantly better competitive employment outcomes than DPA. Competitive employment rates over the 2-year follow-up were 75.0% for IPS and 33.7% for DPA. However, IPS and DPA did not differ on paid employment outcomes. The authors conclude that IPS is more effective than DPA in achieving competitive employment, but not paid employment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment failure and methadone dose in a public methadone maintenance treatment programme in Geneva

PURPOSE: To determine the effect of an anaesthetic with antioxidant potential, propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC susceptibility to peroxidative challenge. METHODS: Propofol was administered by intravenous bolus (2.5 mg.kg-1) and continuous infusion (36 and 72 ml.hr-1 in nine swine; 216 ml.hr-1 in two swine), to achieve serum concentrations between 5 and 30 micrograms.ml-1 for two hours at each rate. Arterial blood sampling was at 0, 10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma propofol concentration, activities of plasma and RBC superoxide dismutase, glutathione peroxidase, glutathione reductase, RBC catalase, and RBC malondialdehyde (MDA) formation in response to ex vivo oxidative challenge with t-butyl hydrogen peroxide (tBHP; 1.5 mM). Antioxidant mechanisms were determined by in vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes exposed to propofol 0-75 microM. The antioxidant potential of propofol was compared with that of alpha-tocopherol utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ). RESULTS: Propofol had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC MDA production over the range of 0-20 micrograms.ml-1 (y = -18.683x + 85.431; R2 = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA levels were 7-12 and 12-20 micrograms.ml-1, respectively. Propofol has a similar effect on human erythrocytes in vitro (R2 = 0.98). CONCLUSION: Propofol antagonises the effects of forced peroxidation of red cells at anaesthetic and sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen derived free radicals in a tocopherol-like manner.     

A randomized controlled trial of the therapeutic workplace for community methadone patients: A partial failure to engage.

The Therapeutic Workplace is an employment-based treatment for drug addiction that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace has promoted abstinence from heroin and cocaine in treatment-resistant mothers in methadone treatment. This study attempted to replicate that effect in crack cocaine users recruited from community-based methadone programs. Participants were randomly assigned to a Therapeutic Workplace (n=22) or usual care control (n=25) group. Therapeutic Workplace participants were invited to work in the workplace and earn vouchers every weekday for 9 months contingent on documented opiate and cocaine abstinence. The two groups did not differ significantly on measures of cocaine or opiate use collected during study participation. Daily attendance and urinalysis results of the Therapeutic Workplace group were analyzed, and only 7 of the 22 participants initiated consistent periods of abstinence and workplace attendance. Two individuals gained access to the workplace on a few days, and 9 participants attempted to gain access to the workplace but never provided a drug-negative urine sample. Possible reasons for differences between the current study and the previous Therapeutic Workplace study are considered. Procedures that increase participant contact with the Therapeutic Workplace and its reinforcement contingencies might increase the likelihood of these individuals being successful in the treatment program. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality disorders and treatment outcome in methadone maintenance patients

This study examined the relationship between personality disorder (PDs) and 7-month treatment outcome in 197 men admitted to methadone maintenance. Subjects reported pervasive improvement, and the amount of improvement did not significantly differ for those subjects with and without PDs. PD subjects entered treatment with more severe self-reported drug, alcohol, psychiatric, and legal problems, and despite progress, remained more problematic in those areas relative to subjects without PDs. Subjects with antisocial PD had admission and 7-month problem status similar to subjects with other PDs. The 7-month urinalysis results for opiates and cocaine showed no significant differences between subjects with and without PDs. Fewer PD subjects stayed in treatment continuously for the 7-month period. Several cluster B PDs-borderline, antisocial, and histrionic-predicted poorest overall outcomes. Methadone-maintained patients with PDs may warrant additional treatment services if they are to approach the functional level of patients without PDs.     

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)     

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)     

The induction and quantitation of methadone dependence in the rat

Slow-release emulsion (SRE) formulations of methadone were used to induce dependence in rats. Animals were exposed to total methadone doses of either 0, 15, 31.25, 62.5, or 125 mg/kg over 48 h. Withdrawal was induced following intraperitoneal challenge with either naloxone (3 mg/kg) or saline (control), and dependence was assessed in terms of the presence/absence of 13 nominated withdrawal behaviors. Three scoring systems to quantify dose-response relationships for withdrawal are described: (1) using the mean number of withdrawal behaviors per animal within each treatment group; (2) using the sum of the percentage of animals within a treatment group displaying each of the withdrawal behaviors; and (3) a modification of these, to further isolate the naloxone-induced component of the withdrawal score, that is, subtraction of data obtained from saline-challenged animals from those of naloxone-challenged rats. In SRE-treated rats, schemes (1) and (2) gave rise to positive dose-response relationships, while scheme (3) resulted in bell-shaped dose-response curves. To validate the proposed scoring systems, each was applied to data obtained from animals made dependent to methadone via administration in the drinking water. The most appropriate system was that utilizing the mean number of withdrawal behaviors; the method is simple, robust, and amenable to statistical analysis.     

Cognitive functioning under moderate and low dosage methadone maintenance

The Wechsler Adult Intelligence Scale (WAIS) was administered to two groups of patients in the Santa Clara County Methadone Maintenance Program who were receiving low and moderate daily stabilized dosages of methadone hydrochloride. In the two separate statistical analyses performed, there were no significant differences found between subtest scores or verbal, performance, and full-scale scores of the groups measured. These results, combined with observations regarding the similarities of WAIS profiles of the two groups, indicate that cognitive functioning as measured by the WAIS was not differentially affected by the two dosages.     

Comparable efficacy of contingency management for cocaine dependence among African American, Hispanic, and White methadone maintenance clients.

Cocaine use is a significant problem among methadone maintenance clients. Contingency management (CM) is a reinforcement-based approach with demonstrated efficacy for reducing cocaine use. This study examines whether the efficacy of CM treatment for cocaine-dependent individuals receiving methadone maintenance for opioid dependence differs by ethnicity. Participants were 191 African American, Hispanic, and White cocaine-dependent methadone maintenance clients, randomly assigned to standard methadone treatment or standard methadone treatment plus CM for 12 weeks. Hispanic participants were younger, less educated, and reported fewer years of cocaine use than did African American and White participants and reported fewer years of heroin use than did African American participants. African American participants were less likely to report a history of psychiatric symptoms or treatment in comparison with Hispanic and White participants. While CM was associated with longer duration of continuous cocaine abstinence and a greater proportion of submitted urine samples negative for cocaine, ethnicity was not related to treatment outcomes, and there was no significant interaction between treatment and ethnicity. CM appears to be an efficacious treatment for cocaine dependence among methadone maintenance clients, regardless of ethnicity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)