Opioid Dependence (opioid + dependence)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Treatment of opioid dependence in adolescents and young adults with extended release naltrexone: preliminary case-series and feasibility

ADDICTION, Issue 9 2010
Marc J. Fishman
ABSTRACT Background Opioid dependence is an increasing problem among adolescents and young adults, but in contrast to the standard in the adult population, adoption of pharmacotherapies has been slow. Extended-release naltrexone (XR-NTX) is a promising treatment that has been receiving increasing interest for adult opioid dependence. Clinical chart abstractions were performed on a convenience sample of 16 serial adolescent and young adult cases (mean age 18.5 years) treated for opioid dependence with XR-NTX who attended at least one out-patient clinical follow-up visit. Case descriptions Of these 16 cases, 10 of 16 (63%) were retained in treatment for at least 4 months and nine of 16 (56%) had a ,good' outcome defined as having substantially decreased opioid use, improvement in at least one psychosocial domain and no new problems due to substance use. Conclusions These descriptive results suggest that XR-NTX in the treatment of adolescents and young adults with opioid dependence is well tolerated over a period of 4 months and feasible in a community-based treatment setting, and associated with good outcomes in a preliminary, small non-controlled case-series. This probably reflects an overall trend towards greater adoption of medication treatments for this population. [source]


Poppy seed tea and opiate abuse in New Zealand

DRUG AND ALCOHOL REVIEW, Issue 2 2007
KLARE BRAYE
Abstract The opium poppy Papaver somniferum contains an array of opiates. There is a variety of methods of preparation that can be used by people with opiate dependence, with patterns of use determined by numerous factors including cost, safety, potency and legal status. The objective of this study was to determine the frequency and nature of poppy seed tea (PST) use by opiate-dependent patients in the form of a written questionnaire. The study took place at the Community Alcohol and Drug Clinic, Wellington, New Zealand, and comprised 24 opiate-dependent patients attending the clinic. A total of 11 of 24 (46%) patients reported having used PST. In five patients currently using PST it represented the major source of opiates, and two had managed to withdraw from use of other opiates with regular PST use. Patients reported a median onset of action of 15 minures and an effect lasting a median of 24 hours. The major limitation of PST use was the foul taste. PST is used commonly by opiate-dependent patients attending an alcohol and drug clinic in New Zealand. The use of PST as the major source of opiates could be considered favourably within ,harm reduction' philosophies, because of its low cost, legal availability and oral route of administration. Conversely, there is the potential for PST to act as a ,gateway drug' by inducing opioid dependence and introducing people to the culture of drug abuse. [source]


Treatment retention in adolescent patients treated with methadone or buprenorphine for opioid dependence: a file review

DRUG AND ALCOHOL REVIEW, Issue 2 2006
JAMES BELL
Abstract The aim of this study was to compare retention and re-entry to treatment between adolescent subjects treated with methadone, those treated with buprenorphine, and those treated with symptomatic (non-opioid) medication only. We used a retrospective file review of all patients aged less than 18 at first presentation for treatment for opioid dependence. The study was conducted at the Langton Centre, Sydney, Australia, an agency specialising in the treatment of alcohol and other drug dependency. Sixty-one adolescents (age range 14,17 years at the time of commencing treatment); mean reported age of initiation of heroin use was 14 ± 1.3 years (range 11,16). Sixty-one per cent were female. The first episode of treatment was methadone maintenance in 20 subjects, buprenorphine in 25, symptomatic medication in 15; one patient underwent assessment only. These 61 subjects had a total of 112 episodes of treatment. Subjects treated with methadone had significantly longer retention in first treatment episode than subjects treated with buprenorphine (mean days 354 vs. 58, p<0.01 by Cox regression) and missed fewer days in the first month (mean 3 vs. 8 days, p<0.05 by t-test). Subsequent re-entry for further treatment occurred in 25% of subjects treated with methadone, 60% buprenorphine and 60% symptomatic medications. Time to reentry after first episode of buprenorphine treatment was significantly shorter than after methadone treatment (p < 0.05 by Kaplan-Meier test). Methadone maintenance appears to have been more effective than buprenorphine at preventing premature drop-out from treatment of adolescent heroin users. [source]


Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system

ADDICTION, Issue 10 2010
Joseph A. Boscarino
ABSTRACT Aims Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. Methods Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. Results Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0,29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age <65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). Conclusion Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts. [source]


Treatment of opioid dependence in adolescents and young adults with extended release naltrexone: preliminary case-series and feasibility

ADDICTION, Issue 9 2010
Marc J. Fishman
ABSTRACT Background Opioid dependence is an increasing problem among adolescents and young adults, but in contrast to the standard in the adult population, adoption of pharmacotherapies has been slow. Extended-release naltrexone (XR-NTX) is a promising treatment that has been receiving increasing interest for adult opioid dependence. Clinical chart abstractions were performed on a convenience sample of 16 serial adolescent and young adult cases (mean age 18.5 years) treated for opioid dependence with XR-NTX who attended at least one out-patient clinical follow-up visit. Case descriptions Of these 16 cases, 10 of 16 (63%) were retained in treatment for at least 4 months and nine of 16 (56%) had a ,good' outcome defined as having substantially decreased opioid use, improvement in at least one psychosocial domain and no new problems due to substance use. Conclusions These descriptive results suggest that XR-NTX in the treatment of adolescents and young adults with opioid dependence is well tolerated over a period of 4 months and feasible in a community-based treatment setting, and associated with good outcomes in a preliminary, small non-controlled case-series. This probably reflects an overall trend towards greater adoption of medication treatments for this population. [source]


Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers

ADDICTION, Issue 4 2010
Sandra D. Comer
ABSTRACT Background Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). Methods Intravenous heroin users (n = 12) lived in the hospital for 8,9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions. Results Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of ,drug liking' and ,desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. Conclusions These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment. [source]


Anabolic,androgenic steroid dependence: an emerging disorder

ADDICTION, Issue 12 2009
Gen Kanayama
ABSTRACT Aims Anabolic,androgenic steroids (AAS) are widely used illicitly to gain muscle and lose body fat. Here we review the accumulating human and animal evidence showing that AAS may cause a distinct dependence syndrome, often associated with adverse psychiatric and medical effects. Method We present an illustrative case of AAS dependence, followed by a summary of the human and animal literature on this topic, based on publications known to us or obtained by searching the PubMed database. Results About 30% of AAS users appear to develop a dependence syndrome, characterized by chronic AAS use despite adverse effects on physical, psychosocial or occupational functioning. AAS dependence shares many features with classical drug dependence. For example, hamsters will self-administer AAS, even to the point of death, and both humans and animals exhibit a well-documented AAS withdrawal syndrome, mediated by neuroendocrine and cortical neurotransmitter systems. AAS dependence may particularly involve opioidergic mechanisms. However, AAS differ from classical drugs in that they produce little immediate reward of acute intoxication, but instead a delayed effect of muscle gains. Thus standard diagnostic criteria for substance dependence, usually crafted for acutely intoxicating drugs, must be adapted slightly for cumulatively acting drugs such as AAS. Conclusions AAS dependence is a valid diagnostic entity, and probably a growing public health problem. AAS dependence may share brain mechanisms with other forms of substance dependence, especially opioid dependence. Future studies are needed to characterize AAS dependence more clearly, identify risk factors for this syndrome and develop treatment strategies. [source]


Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment

ADDICTION, Issue 7 2009
James Bell
ABSTRACT Aim To compare retention in treatment and mortality among people entering methadone and buprenorphine treatment for opioid dependence. Data sources The Pharmaceutical Drugs of Abuse System (PHDAS) database records start- and end-dates of all episodes of methadone and buprenorphine treatment in New South Wales, and the National Death Index (NDI) records all reported deaths. Methods Data linkage study. First entrants to treatment between June 2002 and June 2006 were identified from the PHDAS database. Retention in treatment was compared between methadone and buprenorphine. Names were linked to the NDI database, and ,good matches' were identified. Deaths were classified as occurring during induction, maintenance and either post-methadone or post-buprenorphine, depending on the latest episode of treatment prior to death. The numbers of inductions into treatment, of total person-years spent in each treatment, and person-years post-methadone or buprenorphine, were calculated. Risk of death in different periods, and different treatments, was analysed using Poisson regression. Results A total of 5992 people entered their first episode of treatment,3349 (56%) on buprenorphine, 2643 on methadone. Median retention was significantly longer in methadone (271 days) than buprenorphine (40 days). During induction, the risk of death was lower for buprenorphine (relative risk = 0.114, 95% confidence interval = 0.002,0.938, P = 0.02, Fisher's exact test). Risk of death was lowest during treatment, significantly higher in the first 12 months after leaving both methadone and buprenorphine. Beyond 12 months after leaving treatment, risk of death was non-significantly higher than during treatment. Conclusions Buprenorphine was safer during induction. Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death. [source]


Comparison of costs and utilization among buprenorphine and methadone patients

ADDICTION, Issue 6 2009
Paul G. Barnett
ABSTRACT Aims Buprenorphine is an effective alternative to methadone for treatment of opioid dependence, but economic concerns represent a barrier to implementation. The economic impacts of buprenorphine adoption by the US Veterans Health Administration (VHA) were examined. Design Prescriptions of buprenorphine, methadone treatment visits, health-care utilization and cost, and diagnostic data were obtained for 2005. Findings VHA dispensed buprenorphine to 606 patients and methadone to 8191 other patients during the study year. An analysis that controlled for age and diagnosis found that the mean cost of care for the 6 months after treatment initiation was $11 597 for buprenorphine and $14 921 for methadone (P < 0.001). Cost was not significantly different in subsequent months. The first 6 months of buprenorphine treatment included an average of 66 ambulatory care visits, significantly fewer than the 137 visits in methadone treatment (P < 0.001). In subsequent months, buprenorphine patients had 8.4 visits, significantly fewer than the 21.0 visits of methadone patients (P < 0.001). Compared to new methadone episodes, new buprenorphine episodes had 0.634 times the risk of ending [95% confidence interval 0.547,0.736]. Implementation of buprenorphine treatment was not associated with an influx of new opioid-dependent patients. Conclusion Despite the higher cost of medication, buprenorphine treatment was no more expensive than methadone treatment. VHA methadone treatment costs were higher than reported by other providers. Although new buprenorphine treatment episodes lasted longer than new methadone episodes, buprenorphine is recommended for more adherent patients. [source]


Buprenorphine tapering schedule and illicit opioid use

ADDICTION, Issue 2 2009
Walter Ling
ABSTRACT Aims To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. Design This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. Setting Eleven out-patient treatment programs in 10 US cities. Intervention Non-blinded dosing with Suboxone® during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. Measurements The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. Findings At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). Conclusion For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper. [source]


Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review

ADDICTION, Issue 4 2006
Björn Axel Johansson
ABSTRACT Aims To determine the efficacy of naltrexone in reducing illicit opioid use and the potential moderating role of treatment retention. ,Design First, randomized controlled trials (RCTs) comparing the regimens of treatment using the opioid antagonist, naltrexone, with controls were analysed by meta-analysis for treatment effect with regard to a range of outcome criteria. The degree of heterogeneity was also determined. The moderating effect of other interventions during naltrexone maintenance was then estimated, particularly with regard to their effect on treatment retention. Participants Fifteen studies involving 1071 patients were found. Measurements All available outcomes were analysed in 10 studies of naltrexone versus control (seven placebo) and six studies of randomized psychosocial/psychopharmacological interventions. Findings Significant heterogeneity was found in the efficacy of naltrexone. Level of retention in treatment was found to be a moderator, explaining most of the heterogeneity found. Overall, naltrexone was significantly better than control conditions in reducing the number of opioid-positive urines. This effect was only present in the high retention subgroup for differences in retention. Contingency management (CM) increased retention and naltrexone use, resulting in a reduced number of opioid-positive urines. Conclusion Retention is important to the effect of naltrexone in treating opioid dependence. Contingency management is a promising method of increasing retention. [source]


Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence

ADDICTION, Issue 12 2005
S. Paterson
ABSTRACT Background The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography,mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin. Aims To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine. Design A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data. Findings The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the ,gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use. Conclusions GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes. [source]


Adherence to pharmacotherapy in patients with alcohol and opioid dependence

ADDICTION, Issue 11 2004
Roger D. Weiss
ABSTRACT Aims An important factor that has thus far limited the effectiveness of pharmacotherapies for patients with alcohol and opioid dependence is poor adherence to medication regimens. This paper presents a review of issues related to medication adherence in patients with these substance use disorders. Design and methods A literature review was conducted of English language publications relating to medication adherence among patients with alcohol or opioid dependence. Findings The paper places the topic in the context of adherence difficulties among patients with a variety of chronic medical and psychiatric illnesses. Difficulties measuring adherence are discussed, and strategies to improve medication adherence are reviewed. These include specific interventions that prescribing clinicians can implement in their individual meetings with patients; the use of external reinforcers, such as positive and negative contingencies, and involvement of family members or significant others; and specific prescribing and dosing practices that may improve adherence. Conclusions As the use of pharmacotherapy for substance-dependent patients increases, rigorous and innovative approaches to encourage medication adherence should be sought. [source]


Cost and cost-effectiveness of standard methadone maintenance treatment compared to enriched 180-day methadone detoxification

ADDICTION, Issue 6 2004
Carmen L. Masson
ABSTRACT Aims To compare the cost and cost-effectiveness of methadone maintenance treatment and 180-day methadone detoxification enriched with psychosocial services. Design Randomized controlled study conducted from May 1995 to April 1999. Setting Research clinic in an established drug treatment program. Participants One hundred and seventy-nine adults with diagnosed opioid dependence. Intervention Patients were randomized to methadone maintenance (n = 91), which required monthly 1 hour/week of psychosocial therapy during the first 6 months or 180-day detoxification (n = 88), which required 3 hours/week of psychosocial therapy and 14 education sessions during the first 6 months. Measurements Total health-care costs and self-reported injection drug use. A two-state Markov model was used to estimate quality-adjusted years of survival. Findings Methadone maintenance produced significantly greater reductions in illicit opioid use than 180-day detoxification during the last 6 months of treatment. Total health-care costs were greater for maintenance than detoxification treatment ($7564 versus $6687; P < 0.001). Although study costs were significantly higher for methadone maintenance than detoxification patients ($4739 versus $2855, P < 0.001), detoxification patients incurred significantly higher costs for substance abuse and mental health care received outside the study. Methadone maintenance may provide a modest survival advantage compared with detoxification. The cost per life-year gained is $16 967. Sensitivity analysis revealed a cost-effectiveness ratio of less than $20 000 per quality-adjusted life-year over a wide range of modeling assumptions. Conclusions Compared with enriched detoxification services, methadone maintenance is more effective than enriched detoxification services with a cost-effectiveness ratio within the range of many accepted medical interventions and may provide a survival advantage. Results provide additional support for the use of sustained methadone therapy as opposed to detoxification for treating opioid addiction. [source]


Treatment of opioid dependence in pregnant women

ADDICTION, Issue 8 2000
Gabriele Fischer
First page of article [source]


CLINICAL STUDY: Alterations in pituitary-thyroid axis function among opioid-dependent subjects after acute and protracted abstinence

ADDICTION BIOLOGY, Issue 3 2009
Guo-fu Zhang
ABSTRACT The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence. [source]


GENETIC STUDY: An association of prodynorphin polymorphisms and opioid dependence in females in a Chinese population

ADDICTION BIOLOGY, Issue 3 2009
Toni-Kim Clarke
ABSTRACT Prodynorphin (PDYN) binds to ,-opioid receptors and is known to regulate dopaminergic tone, making this system important for the reinforcing and rewarding properties of drugs of abuse such as opioids. The binding of dynorphins to ,-opioid receptors also produces aversive states that may affect the development of opioid dependence. Recent animal results have shown that PDYNknockout mice show decreased ethanol consumption; however, this finding was restricted to female mice. We were interested to analyse a possible gender specificity of dynorphin effects in humans and to this end three single-nucleotide polymorphisms (SNPs) in PDYN were genotyped in a Chinese population of 484 opioid dependents and 374 controls. An interaction between sex and genotype was found in female opioid dependents. Chi-squared tests for association revealed that the genotype distributions of SNPs rs1997794 (P = 0.019) and rs1022563 (P = 0.006) in the promoter and 3, region of PDYN, respectively, were found to be associated with opioid dependence. Therefore, SNPs in PDYN are significantly associated with the risk of developing opioid dependence; however, this effect may only be seen in females. These data suggest that PDYN polymorphisms should be studied in additional female opioid-dependent populations with an emphasis on the promoter and 3, regions of the gene. [source]


CLINICAL STUDY: Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial

ADDICTION BIOLOGY, Issue 2 2009
Paolo Mannelli
ABSTRACT Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence. [source]


REVIEW: Self-administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls

ADDICTION BIOLOGY, Issue 1 2009
Margaret Haney
ABSTRACT The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs. [source]


Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences

ADDICTION BIOLOGY, Issue 3 2003
PAUL KRABBE
The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p <0.01) and 2 months (RD-GA 93% vs. SMT 33%, p <0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p =0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA. [source]


Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2009
Lambros Messinis
Abstract Rationale Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood. Methods Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin. Results The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients. Conclusion Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study

INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 1 2005
Prof Dr Hans-Ulrich Wittchen
Abstract Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi-stage epidemiological study (COBRA) to address these issues. Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective-longitudinal cohort study of 48 methadone-treated and 48 buprenorphine-treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco-economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone. Copyright © 2005 Whurr Publishers Ltd. [source]


In-vitro and in-vivo characterization of a buprenorphine delivery system

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2006
Sofie R. Kleppner
Buprenorphine is a mu-opioid receptor partial agonist with enhanced safety and comparable efficacy to methadone for treatment of opioid dependence. The sublingual formulation of buprenorphine, approved for treatment of opioid dependence, produces variable buprenorphine blood levels and requires frequent dosing that limits patient compliance. To achieve stable buprenorphine levels that may improve patient outcome, an implantable sustained buprenorphine delivery system was developed. Each implant consists of ethylene vinyl acetate copolymer and 90 mg buprenorphine HCl, and measures 26 mm in length and 2.4 mm in diameter. Steady-state release in-vitro was 0.5 mg/implant/day. In-vivo pharmacokinetics and safety were examined for up to 52 weeks in beagle dogs receiving 8, 16 or 24 subcutaneous implants. Plasma buprenorphine concentrations correlated with the number of implants administered. Peak buprenorphine concentrations were generally reached within 24 h after implantation. Steady-state plasma levels were attained between 3 and 8 weeks, and were maintained for study duration, with a calculated mean release rate of 0.14 ± 0.04 mg/implant/day. There were no test-article-related adverse effects. This delivery system can provide long-term stable systemic buprenorphine levels, and may increase patient compliance, thereby improving outcome for opioid-dependent patients. [source]


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PRESCRIBER, Issue 7 2007
Article first published online: 11 JUL 200
Poor asthma control with off-licence prescribing Children who are prescribed off-licence medications are more likely to have poor asthma control, according to an analysis from Dundee (Br J Gen Practice 2007;57:220-2). The review of 17 163 consultations identified 1050 (6.1 per cent) who received a prescription for an unlicensed use (defined as not licensed for children or the particular age group, or dose not licensed). High doses (4.5 per cent) were more frequent than unlicensed indications (1.9 per cent). Children who received off-label prescriptions reported statistically significantly more symptoms in the day or night, symptoms during activity, and increased use of daily short-acting beta2-agonists. The authors note that off-label prescribing appears to be increasing. Atkins diet most effective over one year? The ultra low-carbohydrate, high-protein Atkins diet achieved greater weight loss than other popular diets in overweight women over one year, say US investigators (J Am Med Assoc 2007;297:969-77). The study compared the Atkins diet with three diets designed as low- or very high-carbohydrate, or based on USA nutritional guidance, in 311 women with body mass index 27-40. After one year, mean weight loss was 4.7kg with the Atkins diet , significantly greater than with the low- carbohydrate diet (1.6kg) but not compared with very high-carbohydrate (2.2kg) or the nutrition-based diet (2.6kg). Metabolic endpoints were comparable or more favourable in women using the Atkins diet. Androgen therapy linked to gum disease The majority of men treated with androgen deprivation therapy for prostate cancer are more likely to have periodontal disease (J Urol 2007;177:921-4). After controlling for risk factors, the prevalence of periodontal disease was 80.5 per cent among treated men compared with 3.7 per cent in matched controls not receiving treatment. There was no difference in bone mineral density between the groups but plaque scores were significantly higher among treated men. Food Commission rebuts MHRA on additives An independent watchdog has not accepted the MHRA's justification for including certain additives in medicines for children. The Food Commission (www.foodcomm.org.uk) found that most medicines for children contained additives, some of which , including azo dyes and benzoates , are not permitted in food. The Commission called on the pharmaceutical industry to stop using ,questionable additives'. The MHRA stated that the licensing process takes into account the likely exposure to excipients that are considered essential to make medicines palatable to children. Colouring helps children to identify the correct medicine, and preservatives ensure a reasonable shelf-life. A list of additives is included in the product's summary of product characteristics and patient information leaflet. In response, the Commission states: , , it is quite possible to flavour medicines with natural oils or extracts, and natural colourings such as beetroot and beta-carotene can be used instead of azo dyes. If parents were advised to give these medicinal products at mealtimes the manufacturers could also add a little sugar to sweeten their products, rather than relying on artificial sweeteners.' All triptans the same? There is no economic case for choosing one triptan over another and no evidence for preferring a particular triptan for adults, a systematic review has concluded. The Canadian Agency for Drugs and Technologies in Health (www.cadth.ca) found that published trials had compared most triptans with sumatriptan but not with one another, and most economic evaluations were flawed. New drug for HIV Janssen-Cilag has introduced darunavir (Prezista), a new protease inhibitor for the treatment of HIV infection. Licensed for highly pre- treated patients in whom more than one other pro- tease inhibitor regimen has failed, darunavir must be co-administered with ritonavir (Norvir). A month's treatment at the recommended dose of 600mg twice daily costs £446.70. Variation in liquid captopril for children The NHS uses a wide range of liquid formulations of captopril to treat children with heart failure , with no assurance of their bioequivalence (Arch Dis Child 2007; published online 15 March. doi: 10.1136/adc.2006.109389). Specialists in Leicester surveyed 13 tertiary paediatric cardiac centres and 13 hospitals that referred patients to them. Only three tertiary centres supplied the same liquid for-mulation of captopril as their referring hospitals. Four hospitals supplied tablets for crushing and dissolving in water; the other hospitals and centres used a total of nine different formulations. The authors say the formulations had widely varying shelf-lives, determined empirically in all but one case, and were used interchangeably despite a lack of quality control data to establish their bioequivalence. QOF CVD targets not good enough for GPs Two-thirds of GPs want Quality Outcome Framework (QOF) targets for cardiovascular disease brought into line with those of the Joint British Societies latest guidance (JBS2), according to a survey by doctor.net.uk. The survey of 1000 GPs showed that 88 per cent were aware of the JBS2 guidelines and most were already implementing the targets for lipids, blood pressure and blood glucose in some form; however, only 55 per cent were implementing the JBS2 obesity target and 14 per cent were implementing screening for the over-40s. The JBS2 target for lipids in at-risk patients is <4mmol per litre total cholesterol and <2 mmol per litre LDL-cholesterol, compared with <5 and <3mmol per litre respectively in QOF and the NSF. The survey was commissioned by Merck Sharp & Dohme and Schering- Plough. Fracture warning Following warnings in the US that rosiglitazone (Avandia) is associated with an increased risk of fractures in women, Takeda has advised prescribers that pioglitazone (Actos) carries a similar risk. An analysis of the company's clinical trials database has revealed an excess risk of fractures of bones below the elbow and knee. The incidence was similar to the excess risk associated with rosiglitazone and also confined to women. Scottish approvals The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved for use within NHS Scotland the sublingual tablet formulation buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. It has also approved the combined formulation of valsartan and amlodipine (Exforge) and the restricted use of the If inhibitor ivabradine (Procoralan). [source]


Implication of Gender Differences in Heroin-Assisted Treatment: Results from the German Randomized Controlled Trial

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2010
Francisco José Eiroá-Orosa MSc
Despite a lower prevalence of opioid dependence among females, drug-related problems and risk factors such as prostitution have a negative effect for women in treatment. This study was conducted with the purpose of analyzing gender differences in the German trial on heroin-assisted treatment (HAT), which compared HAT with methadone maintenance treatment (MMT). Significant baseline gender differences were found, with females showing a greater extent of mental distress. Differences in retention and outcome were significant for male patients, but no differences between treatment options were found for female patients. Ongoing prostitution was found to influence drug use outcomes. Other outcome criteria may need to be stressed when assessing the effect of HAT for women.,(Am J Addict 2010;00:1,7) [source]


Auditory P300 Event-Related Potentials and Neurocognitive Functions in Opioid Dependent Men and Their Brothers

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 3 2009
Shubh Mohan Singh MD
Event-related-potentials (especially P300) and cognitive functioning as potential endophenotypes have not been studied in opioid dependence. We compared auditory P300 and cognitive functions in opioid-dependent men, their brothers and normal controls in an exploratory study with a view to find shared genetic factors in the development of opioid dependence. Twenty abstinent opioid-dependent males, their brothers and twenty matched controls were administered Wisconsin card sorting test (WCST), digit span test, trail making test-B, and auditory event-related potentials (P300) from an oddball task were recorded. The opioid dependent group performed the worst, the brothers group was intermediate, and the control group performed the best on tests of WCST, digit span and trail making test-B. The opioid dependent group had the smallest amplitudes and longest latencies of P300, and was followed by the brothers group who had an intermediate position and the control group who had the largest amplitudes and the shortest latencies. P300 and executive neurocognitive functions can be considered endophenotypes for the genetic study of vulnerability to opioid dependence. These are reflective of executive dysfunction and disrupted behavioral inhibition and the intermediate position of brothers suggests a common genetic substrate as a component of the etiology. [source]


Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 2 2009
Paolo Mannelli MD
Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence. [source]


Comorbid Psychiatric Diagnoses and Their Association with Cocaine-Induced Psychosis in Cocaine-Dependent Subjects

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 5 2007
Yi-Lang Tang MD
Comorbidity between drug abuse and mental illness is very common, but the association of such comorbidity with specific responses to drugs of abuse remains obscure. The current study examined the relationship between the presence of non-psychotic Axis I psychiatric diagnoses and the frequency and severity of cocaine-induced psychosis. We interviewed 243 unrelated cocaine-dependent adults [37% European American (EA), 52.3% African American (AA); 58.8% male] using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) to establish DSM-IV diagnoses, and two instruments for the identification of cocaine-induced paranoia, the Cocaine Experience Questionnaire (CEQ) and the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP). Comorbid substance use and psychiatric disorders were common in this cocaine-dependent sample. Ninety percent of subjects met criteria for substance use disorders other than cocaine dependence; common non-substance-use disorders included antisocial personality disorder (ASPD), adult ASPD, major depression, and attention deficit-hyperactivity disorder (ADHD). Comorbid opioid dependence was more common in EA subjects than in AA participants. After correction for multiple comparisons, a lifetime diagnosis of ADHD was associated with the categorical presence of CIP (p = 0.007), as well as significantly more severe CIP symptoms. Comorbid substance use and psychiatric disorders are very common among individuals with cocaine dependence. Comorbid ADHD increases the odds of an individual endorsing CIP, suggesting some common basis for these phenomena. [source]


Pharmacologic Treatments for Heroin and Cocaine Dependence

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 2003
Herbert D. Kleber M.D.
Given the difficulty of achieving sustained recovery, pharmacotherapy of opioid and cocaine addiction is more effective when combined with behavioral and psychosocial approaches. Effective pharmacotherapies for opioid dependence and withdrawal include methadone, L-alpha acetylmethadol (LAAM), naltrexone, buprenorphine, and clonidine. Treatment of cocaine addiction includes anti-craving agents, dopamine agonists or blocking agents, antidepressants, and treatment of co-morbid psychiatric disorders, but all with mixed results. In this paper, we discuss the use of medication in the context of general principles of opioid and cocaine addiction treatment. Both established medications and promising directions in pharmacotherapy will be addressed. [source]


Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neurons

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003
Eduardo Ruiz-Durántez
The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) or valldemossine (10 mg kg,1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. After chronic administration of 2-BFI (10 mg kg,1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg,1, i.p.) or valldemossine (10 mg kg,1, i.p.) were used. Acute administration of 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) but not valldemossine (40 mg kg,1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5 -enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 ,M) was applied to rat brain slices (EC50 increased by 5.6; P<0.05). The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance. British Journal of Pharmacology (2003) 138, 494,500. doi:10.1038/sj.bjp.0705052 [source]